Difference between revisions of "Colorectal cancer, MSI-H or dMMR"

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{{#lst:Section editor transclusions|gi}}
 
{{#lst:Section editor transclusions|gi}}
 
<big>Note: this page has regimens specific to MSI-H/dMMR colon cancer.   
 
<big>Note: this page has regimens specific to MSI-H/dMMR colon cancer.   
−
 
 
*See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.</big>
 
*See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.</big>
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
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|}
 
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
−
 
 
=Advanced or metastatic disease, first-line=
 
=Advanced or metastatic disease, first-line=
 
==Atezolizumab monotherapy {{#subobject:egac61|Regimen=1}}==
 
==Atezolizumab monotherapy {{#subobject:egac61|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:abgc1l|Variant=1}}===
 
===Regimen {{#subobject:abgc1l|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
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|}
 
|}
 
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The mFOLFOX6-B arm was closed early.''
 
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The mFOLFOX6-B arm was closed early.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Atezolizumab (Tecentriq)]]
 
*[[Atezolizumab (Tecentriq)]]
 +
</div></div>
 
===References===
 
===References===
 
#'''COMMIT:''' NCT02997228
 
#'''COMMIT:''' NCT02997228
−
 
 
==FOLFIRI {{#subobject:ebcf30|Regimen=1}}==
 
==FOLFIRI {{#subobject:ebcf30|Regimen=1}}==
−
 
 
FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
 
FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:abe1bd|Variant=1}}===
 
===Regimen {{#subobject:abe1bd|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 58: Line 56:
 
|}
 
|}
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*MSI-H/dMMR mCRC as determined locally
 
*MSI-H/dMMR mCRC as determined locally
−
 
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
 
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with irinotecan'''
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with irinotecan'''
 
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1, '''given first, with leucovorin'''
 
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1, '''given first, with leucovorin'''
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
 +
</div></div>
 
===References===
 
===References===
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
Line 73: Line 72:
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
# '''CheckMate 8HW:''' NCT04008030
 
# '''CheckMate 8HW:''' NCT04008030
−
 
 
==FOLFIRI & Bevacizumab {{#subobject:80d6b8|Regimen=1}}==
 
==FOLFIRI & Bevacizumab {{#subobject:80d6b8|Regimen=1}}==
−
 
 
FOLFIRI & Bevacizumab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Bevacizumab
 
FOLFIRI & Bevacizumab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Bevacizumab
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:28b67a|Variant=1}}===
 
===Regimen {{#subobject:28b67a|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 93: Line 91:
 
|}
 
|}
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*MSI-H/dMMR mCRC as determined locally
 
*MSI-H/dMMR mCRC as determined locally
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
 
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with irinotecan'''
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with irinotecan'''
 
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
Line 102: Line 102:
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1, '''given second'''
 
*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1, '''given second'''
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
 +
</div></div>
 
===References===
 
===References===
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
## '''HRQoL analysis:''' Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. [https://doi.org/10.1016/s1470-2045(21)00064-4 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/33812497/ PubMed]
 
## '''HRQoL analysis:''' Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. [https://doi.org/10.1016/s1470-2045(21)00064-4 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/33812497/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
−
 
 
==mFOLFOX6 {{#subobject:e4bda7|Regimen=1}}==
 
==mFOLFOX6 {{#subobject:e4bda7|Regimen=1}}==
−
 
 
mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 
mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:db877a|Variant=1}}===
 
===Regimen {{#subobject:db877a|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
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|}
 
|}
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*MSI-H/dMMR mCRC as determined locally
 
*MSI-H/dMMR mCRC as determined locally
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
 
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
Line 142: Line 143:
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
# '''ATOMIC:''' NCT02912559
 
# '''ATOMIC:''' NCT02912559
−
 
 
==mFOLFOX6-B {{#subobject:b74416|Regimen=1}}==
 
==mFOLFOX6-B {{#subobject:b74416|Regimen=1}}==
−
 
 
mFOLFOX6-B: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>B</u>'''evacizumab
 
mFOLFOX6-B: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>B</u>'''evacizumab
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:db572g|Variant=1}}===
 
===Regimen {{#subobject:db572g|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 162: Line 162:
 
|}
 
|}
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*MSI-H/dMMR mCRC as determined locally
 
*MSI-H/dMMR mCRC as determined locally
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
Line 170: Line 173:
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1
 
*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
 +
</div></div>
 
===References===
 
===References===
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
## '''HRQoL analysis:''' Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. [https://doi.org/10.1016/s1470-2045(21)00064-4 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/33812497/ PubMed]
 
## '''HRQoL analysis:''' Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. [https://doi.org/10.1016/s1470-2045(21)00064-4 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/33812497/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
−
 
 
==Pembrolizumab monotherapy {{#subobject:5aa59d|Regimen=1}}==
 
==Pembrolizumab monotherapy {{#subobject:5aa59d|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:3af038|Variant=1}}===
 
===Regimen {{#subobject:3af038|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 200: Line 202:
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''<br>
 
''<sup>1</sup>Reported efficacy is based on the 2022 update.''<br>
 
''Inclusion criteria: ECOG PS 0 or 1''
 
''Inclusion criteria: ECOG PS 0 or 1''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*MSI-H/dMMR mCRC as determined locally
 
*MSI-H/dMMR mCRC as determined locally
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
 
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
−
 
 
'''21-day cycle for up to 2 years'''
 
'''21-day cycle for up to 2 years'''
−
 
+
</div></div>
 
===References===
 
===References===
−
 
 
<!-- #'''Abstract:''' Andre T, Shiu KK, KIM TW, Jensen BV, Jensen LH, Punt CJA, Smith DM, Garcia-Carbonero R, Benavides M, Gibbs P, Fouchardiere CDL, Rivera F, Elez E, Bendell JC, Le DT, Yoshino T, Yang P, Farooqui MZH, Marinello P, Diaz LA. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. J Clin Oncol 38: 2020 (suppl; abstr LBA4) [https://meetinglibrary.asco.org/record/186928 Link to abstract] -->
 
<!-- #'''Abstract:''' Andre T, Shiu KK, KIM TW, Jensen BV, Jensen LH, Punt CJA, Smith DM, Garcia-Carbonero R, Benavides M, Gibbs P, Fouchardiere CDL, Rivera F, Elez E, Bendell JC, Le DT, Yoshino T, Yang P, Farooqui MZH, Marinello P, Diaz LA. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. J Clin Oncol 38: 2020 (suppl; abstr LBA4) [https://meetinglibrary.asco.org/record/186928 Link to abstract] -->
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
# '''KEYNOTE-177:''' André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. [https://doi.org/10.1056/nejmoa2017699 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33264544 PubMed] NCT02563002
 
## '''HRQoL analysis:''' Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. [https://doi.org/10.1016/s1470-2045(21)00064-4 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/33812497/ PubMed]
 
## '''HRQoL analysis:''' Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. [https://doi.org/10.1016/s1470-2045(21)00064-4 link to orginal article] [https://pubmed.ncbi.nlm.nih.gov/33812497/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
 
## '''Update:''' Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. [https://doi.org/10.1016/s1470-2045(22)00197-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35427471/ PubMed]
−
 
 
=Advanced or metastatic disease, subsequent lines of therapy=
 
=Advanced or metastatic disease, subsequent lines of therapy=
 
==Ipilimumab & Nivolumab {{#subobject:517ff0|Regimen=1}}==
 
==Ipilimumab & Nivolumab {{#subobject:517ff0|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:3a481c|Variant=1}}===
 
===Regimen {{#subobject:3a481c|Variant=1}}===
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
Line 229: Line 230:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Ipilimumab (Yervoy)]] as follows:
 
*[[Ipilimumab (Yervoy)]] as follows:
 
**Cycles 1 to 4: 1 mg/kg IV once on day 1
 
**Cycles 1 to 4: 1 mg/kg IV once on day 1
 
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
 
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
−
 
 
'''21-day cycle for 4 cycles, then 14-day cycles'''
 
'''21-day cycle for 4 cycles, then 14-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
 
#'''CheckMate 142:''' Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. [https://doi.org/10.1016/S1470-2045(17)30422-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207072/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28734759 PubMed] NCT02060188
 
#'''CheckMate 142:''' Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. [https://doi.org/10.1016/S1470-2045(17)30422-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207072/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28734759 PubMed] NCT02060188
 
## '''Update:''' Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. Epub 2018 Jan 20. [https://doi.org/10.1200/JCO.2017.76.9901 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29355075 PubMed]
 
## '''Update:''' Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. Epub 2018 Jan 20. [https://doi.org/10.1200/JCO.2017.76.9901 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29355075 PubMed]
 
## '''Update:''' André T, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Abdullaev S, Memaj A, Lei M, Dixon M, Kopetz S, Overman MJ. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 2022 Jun 25:S0923-7534(22)01737-9. Epub ahead of print. [https://doi.org/10.1016/j.annonc.2022.06.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35764271/ PubMed]
 
## '''Update:''' André T, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Abdullaev S, Memaj A, Lei M, Dixon M, Kopetz S, Overman MJ. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 2022 Jun 25:S0923-7534(22)01737-9. Epub ahead of print. [https://doi.org/10.1016/j.annonc.2022.06.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35764271/ PubMed]
−
 
 
==Nivolumab monotherapy {{#subobject:ac98g4|Regimen=1}}==
 
==Nivolumab monotherapy {{#subobject:ac98g4|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:91abt2|Variant=1}}===
 
===Regimen {{#subobject:91abt2|Variant=1}}===
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
Line 254: Line 254:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*dMMR or MSI-H colorectal cancer.
 
*dMMR or MSI-H colorectal cancer.
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
 
 
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
 
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
 
 
#'''CheckMate 142:''' Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. [https://doi.org/10.1016/S1470-2045(17)30422-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207072/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28734759 PubMed] NCT02060188
 
#'''CheckMate 142:''' Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. [https://doi.org/10.1016/S1470-2045(17)30422-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207072/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28734759 PubMed] NCT02060188
 
## '''Update:''' Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. Epub 2018 Jan 20. [https://doi.org/10.1200/JCO.2017.76.9901 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29355075 PubMed]
 
## '''Update:''' Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. Epub 2018 Jan 20. [https://doi.org/10.1200/JCO.2017.76.9901 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29355075 PubMed]
 
## '''Update:''' André T, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Abdullaev S, Memaj A, Lei M, Dixon M, Kopetz S, Overman MJ. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 2022 Jun 25:S0923-7534(22)01737-9. Epub ahead of print. [https://doi.org/10.1016/j.annonc.2022.06.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35764271/ PubMed]
 
## '''Update:''' André T, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Abdullaev S, Memaj A, Lei M, Dixon M, Kopetz S, Overman MJ. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 2022 Jun 25:S0923-7534(22)01737-9. Epub ahead of print. [https://doi.org/10.1016/j.annonc.2022.06.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35764271/ PubMed]
−
 
 
==Pembrolizumab monotherapy {{#subobject:ac2c94|Regimen=1}}==
 
==Pembrolizumab monotherapy {{#subobject:ac2c94|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #1, flat dose {{#subobject:fe5344|Variant=1}}===
 
===Regimen variant #1, flat dose {{#subobject:fe5344|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
Line 281: Line 280:
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*dMMR or MSI-H tumors
 
*dMMR or MSI-H tumors
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
 
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
−
 
 
'''21-day cycle for up to 35 cycles (2 years)'''
 
'''21-day cycle for up to 35 cycles (2 years)'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, weight-based {{#subobject:B34AD4|Variant=1}}===
 
===Regimen variant #2, weight-based {{#subobject:B34AD4|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
Line 301: Line 302:
 
|}
 
|}
 
''Note: this study only demonstrated a clear benefit for mismatch repair-deficient colorectal cancers. Please be aware that the FDA-approved, recommended pembrolizumab dose in the package insert is 200 mg for adults, 2 mg/kg (maximum dose 200 mg) for children, given every 3 weeks.''
 
''Note: this study only demonstrated a clear benefit for mismatch repair-deficient colorectal cancers. Please be aware that the FDA-approved, recommended pembrolizumab dose in the package insert is 200 mg for adults, 2 mg/kg (maximum dose 200 mg) for children, given every 3 weeks.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
 
*dMMR or MSI-H tumors
 
*dMMR or MSI-H tumors
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
 
 
*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
 
*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
 
 
#'''KEYNOTE-016:''' Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. [https://doi.org/10.1056/NEJMoa1500596 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26028255 PubMed] NCT01876511
 
#'''KEYNOTE-016:''' Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. [https://doi.org/10.1056/NEJMoa1500596 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26028255 PubMed] NCT01876511
 
##'''Update:''' Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. [http://science.sciencemag.org/content/357/6349/409.long link to original article]  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28596308 PubMed]
 
##'''Update:''' Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. [http://science.sciencemag.org/content/357/6349/409.long link to original article]  [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28596308 PubMed]
 
<!-- #'''Abstract:''' Dung T. Le, Takayuki Yoshino, Dirk Jäger, Thierry Andre, Johanna C. Bendell, Ruixue Wang... SoonMo Peter Kang, Minori Koshiji, Luis A. Diaz. KEYNOTE-164: Phase II study of pembrolizumab (MK-3475) for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma. J Clin Oncol [https://doi.org/10.1200/jco.2016.34.4_suppl.tps787 abstract TPS787] and [https://doi.org/10.1200/JCO.2016.34.15_suppl.TPS3631 abstract TPS3631] -->
 
<!-- #'''Abstract:''' Dung T. Le, Takayuki Yoshino, Dirk Jäger, Thierry Andre, Johanna C. Bendell, Ruixue Wang... SoonMo Peter Kang, Minori Koshiji, Luis A. Diaz. KEYNOTE-164: Phase II study of pembrolizumab (MK-3475) for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma. J Clin Oncol [https://doi.org/10.1200/jco.2016.34.4_suppl.tps787 abstract TPS787] and [https://doi.org/10.1200/JCO.2016.34.15_suppl.TPS3631 abstract TPS3631] -->
 
#'''KEYNOTE-164:''' Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, Guimbaud R, Taniguchi H, Elez E, Al-Batran SE, Boland PM, Crocenzi T, Atreya CE, Cui Y, Dai T, Marinello P, Diaz LA Jr, André T. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol. 2020 Jan 1;38(1):11-19. Epub 2019 Nov 14. [https://doi.org/10.1200/jco.19.02107 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7031958/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31725351/ PubMed] NCT02460198
 
#'''KEYNOTE-164:''' Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, Guimbaud R, Taniguchi H, Elez E, Al-Batran SE, Boland PM, Crocenzi T, Atreya CE, Cui Y, Dai T, Marinello P, Diaz LA Jr, André T. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol. 2020 Jan 1;38(1):11-19. Epub 2019 Nov 14. [https://doi.org/10.1200/jco.19.02107 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7031958/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31725351/ PubMed] NCT02460198
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[[Category:Colon cancer regimens]]
 
[[Category:Colon cancer regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Colorectal cancers]]
 
[[Category:Colorectal cancers]]

Revision as of 01:03, 26 January 2023

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Section editor transclusions Note: this page has regimens specific to MSI-H/dMMR colon cancer.

9 regimens on this page
10 variants on this page


Advanced or metastatic disease, first-line

Atezolizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (COMMIT) 2017-ongoing Phase 3 (C) 1. mFOLFOX6-B
2. mFOLFOX6, Atezolizumab, Bevacizumab 		In progress

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The mFOLFOX6-B arm was closed early.

Immunotherapy

References

  1. COMMIT: NCT02997228

FOLFIRI

FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
André et al. 2020 (KEYNOTE-177) 2016-2018 Phase 3 (C) Pembrolizumab Might have inferior OS1

1Reported efficacy is based on the 2022 update.

Biomarker eligibility criteria

  • MSI-H/dMMR mCRC as determined locally

Chemotherapy

  • Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given first, with irinotecan
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
  • Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given first, with leucovorin

14-day cycles

References

  1. KEYNOTE-177: André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. link to original article contains dosing details in manuscript PubMed NCT02563002
    1. HRQoL analysis: Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. link to orginal article PubMed
    2. Update: Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. link to original article PubMed
  2. CheckMate 8HW: NCT04008030

FOLFIRI & Bevacizumab

FOLFIRI & Bevacizumab: FOLinic acid, Fluorouracil, IRInotecan, Bevacizumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
André et al. 2020 (KEYNOTE-177) 2016-2018 Phase 3 (C) Pembrolizumab Might have inferior OS1

1Reported efficacy is based on the 2022 update.

Biomarker eligibility criteria

  • MSI-H/dMMR mCRC as determined locally

Chemotherapy

  • Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given first, with irinotecan
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given third (total dose per cycle: 2800 mg/m2)
  • Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given first, with leucovorin

Targeted therapy

14-day cycles

References

  1. KEYNOTE-177: André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. link to original article contains dosing details in manuscript PubMed NCT02563002
    1. HRQoL analysis: Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. link to orginal article PubMed
    2. Update: Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. link to original article PubMed

mFOLFOX6

mFOLFOX6: modified FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
André et al. 2020 (KEYNOTE-177) 2016-2018 Phase 3 (C) Pembrolizumab Might have inferior OS1

1Reported efficacy is based on the 2022 update.

Biomarker eligibility criteria

  • MSI-H/dMMR mCRC as determined locally

Chemotherapy

14-day cycles

References

  1. KEYNOTE-177: André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. link to original article contains dosing details in manuscript PubMed NCT02563002
    1. HRQoL analysis: Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. link to orginal article PubMed
    2. Update: Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. link to original article PubMed
  2. ATOMIC: NCT02912559

mFOLFOX6-B

mFOLFOX6-B: modified FOLinic acid, Fluorouracil, OXaliplatin, Bevacizumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
André et al. 2020 (KEYNOTE-177) 2016-2018 Phase 3 (C) Pembrolizumab Might have inferior OS1

1Reported efficacy is based on the 2022 update.

Biomarker eligibility criteria

  • MSI-H/dMMR mCRC as determined locally

Chemotherapy

Targeted therapy

14-day cycles

References

  1. KEYNOTE-177: André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. link to original article contains dosing details in manuscript PubMed NCT02563002
    1. HRQoL analysis: Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. link to orginal article PubMed
    2. Update: Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. link to original article PubMed

Pembrolizumab monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
André et al. 2020 (KEYNOTE-177) 2016-2018 Phase 3 (E-RT-switch-ooc) Investigator's choice of:
1a. mFOLFOX6
1b. mFOLFOX6-B
1c. mFOLFOX6 & Cetuximab
1d. FOLFIRI
1e. FOLFIRI & Bevacizumab
1f. FOLFIRI & Cetuximab 		Might have superior OS1
Median OS: NYR vs 36.7 mo
(HR 0.74, 95% CI 0.53-1.03)

1Reported efficacy is based on the 2022 update.
Inclusion criteria: ECOG PS 0 or 1

Biomarker eligibility criteria

  • MSI-H/dMMR mCRC as determined locally

Immunotherapy

21-day cycle for up to 2 years

References

  1. KEYNOTE-177: André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. link to original article contains dosing details in manuscript PubMed NCT02563002
    1. HRQoL analysis: Andre T, Amonkar M, Norquist JM, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith D, Garcia-Carbonero R, Sevilla I, De La Fouchardiere C, Rivera F, Elez E, Diaz LA Jr, Yoshino T, Van Cutsem E, Yang P, Farooqui M, Le DT. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):665-677. Epub 2021 Apr 1. link to orginal article PubMed
    2. Update: Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May 1;23(5):659-670. Epub 2022 Apr 12. link to original article PubMed

Advanced or metastatic disease, subsequent lines of therapy

Ipilimumab & Nivolumab

Regimen

Study Years of enrollment Evidence
Overman et al. 2017 (CheckMate 142) 2014-2016 Phase 2 (RT)

Immunotherapy

21-day cycle for 4 cycles, then 14-day cycles

References

  1. CheckMate 142: Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. link to original article link to PMC article contains dosing details in abstract PubMed NCT02060188
    1. Update: Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. Epub 2018 Jan 20. link to original article contains dosing details in abstract PubMed
    2. Update: André T, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Abdullaev S, Memaj A, Lei M, Dixon M, Kopetz S, Overman MJ. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 2022 Jun 25:S0923-7534(22)01737-9. Epub ahead of print. link to original article PubMed

Nivolumab monotherapy

Regimen

Study Years of enrollment Evidence
Overman et al. 2017 (CheckMate 142) 2014-2016 Phase 2 (RT)

Biomarker eligibility criteria

  • dMMR or MSI-H colorectal cancer.

Immunotherapy

14-day cycles

References

  1. CheckMate 142: Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. Epub 2017 Jul 19. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. link to original article link to PMC article contains dosing details in abstract PubMed NCT02060188
    1. Update: Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. Epub 2018 Jan 20. link to original article contains dosing details in abstract PubMed
    2. Update: André T, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Abdullaev S, Memaj A, Lei M, Dixon M, Kopetz S, Overman MJ. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 2022 Jun 25:S0923-7534(22)01737-9. Epub ahead of print. link to original article PubMed

Pembrolizumab monotherapy

Regimen variant #1, flat dose

Study Years of enrollment Evidence
Le et al. 2019 (KEYNOTE-164) 2015-2017 Phase 2 (RT)

Biomarker eligibility criteria

  • dMMR or MSI-H tumors

Immunotherapy

21-day cycle for up to 35 cycles (2 years)


Regimen variant #2, weight-based

Study Years of enrollment Evidence
Le et al. 2015 (KEYNOTE-016) 2013-2015 Phase 2

Note: this study only demonstrated a clear benefit for mismatch repair-deficient colorectal cancers. Please be aware that the FDA-approved, recommended pembrolizumab dose in the package insert is 200 mg for adults, 2 mg/kg (maximum dose 200 mg) for children, given every 3 weeks.

Biomarker eligibility criteria

  • dMMR or MSI-H tumors

Immunotherapy

14-day cycles

References

  1. KEYNOTE-016: Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. link to original article contains dosing details in abstract link to PMC article PubMed NCT01876511
    1. Update: Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. link to original article link to PMC article contains dosing details in supplement PubMed
  2. KEYNOTE-164: Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, Guimbaud R, Taniguchi H, Elez E, Al-Batran SE, Boland PM, Crocenzi T, Atreya CE, Cui Y, Dai T, Marinello P, Diaz LA Jr, André T. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol. 2020 Jan 1;38(1):11-19. Epub 2019 Nov 14. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02460198
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