Revision as of 12:06, 24 January 2023

3 regimens on this page 3 variants on this page

Note: this page has regimens which are specific to pancreatic cancer that is BRCA-mutated. Please see the main pancreatic cancer page for other chemotherapy regimens.

Advanced or metastatic disease, first-line

Cisplatin & Gemcitabine (GC)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
O'Reilly et al. 2020 (MSKCC 12-045)	2014-2018	Randomized Phase 2 (C)	GC & Veliparib	Did not meet primary endpoint of RR

Selected inclusion criteria: germline BRCA1/2 or PALB2 mutation and previously untreated stage III-IV pancreatic adenocarcinoma. The addition of veliparib did not improve RR.

Biomarker eligibility criteria

Germline BRCA1/2 or PALB2+ mutation

Chemotherapy

Cisplatin (Platinol) 25 mg/m² IV once per day on days 3 & 10
Gemcitabine (Gemzar) 600 mg/m² IV once per day on days 3 & 10

21-day cycles

References

MSKCC 12-045: O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen D. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 01;38:1378-1388. link to original article link to PMC article PubMed NCT01585805

Maintenance after first-line therapy

Olaparib monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Golan et al. 2019 (POLO)	2015-2019	Phase 3 (E-RT-esc)	Placebo	Superior PFS Median PFS: 7.4 vs 3.8 mo (HR 0.53, 95% CI 0.35-0.82)

Selected inclusion criteria: germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy.

Biomarker eligibility criteria

Germline BRCA1 or BRCA2 mutation

Preceding treatment

Platinum-based chemotherapy for at least 16 weeks

Targeted therapy

Olaparib (Lynparza) 300 mg PO twice per day

Continued indefinitely

References

POLO: Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. link to original article contains dosing details in abstract link to PMC article PubMed NCT02184195
1. Update: Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. link to original article PubMed

Placebo

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Golan et al. 2019 (POLO)	2015-2019	Phase 3 (C)	Olaparib	Inferior PFS

Preceding treatment

Platinum-based chemotherapy for at least 16 weeks

References

POLO: Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. link to original article link to PMC article PubMed NCT02184195
1. Update: Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. link to original article PubMed

Metastatic disease, refractory

Olaparib monotherapy

Regimen

Study	Evidence
Kaufman et al. 2014 (Study 42)	Phase 2

Biomarker eligibility criteria

Germline BRCA1/2 mutations

Prior treatment criteria

Gemcitabine, with progression

Targeted therapy

Olaparib (Lynparza) 400 mg PO twice per day

Continued indefinitely

References

Study 42: Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01078662

Additional resources

@@ Line 12: / Line 12: @@
 {{TOC limit|limit=3}}
 =Advanced or metastatic disease, first-line=
 ==Cisplatin & Gemcitabine (GC) {{#subobject:344hc7|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3ab23a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 32: / Line 30: @@
 |}
 ''Selected inclusion criteria: germline BRCA1/2 or PALB2 mutation and previously untreated stage III-IV pancreatic adenocarcinoma''. The addition of veliparib did not improve RR.
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Germline BRCA1/2 or PALB2+ mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 3 & 10
 *[[Gemcitabine (Gemzar)]] 600 mg/m<sup>2</sup> IV once per day on days 3 & 10
 '''21-day cycles'''
+</div></div>
 ===References===
 #'''MSKCC 12-045:''' O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen D. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline ''BRCA/PALB2'' Mutation. J Clin Oncol. 2020 May 01;38:1378-1388. [https://doi.org/10.1200/jco.19.02931 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7193749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31976786/ PubMed] NCT01585805
 =Maintenance after first-line therapy=
 ==Olaparib monotherapy {{#subobject:388hc7|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3ab86a|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 71: / Line 65: @@
 |}
 ''Selected inclusion criteria: germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy.''
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Germline BRCA1 or BRCA2  mutation
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Regimen_classes#Platinum-based_regimen|Platinum-based chemotherapy]] for at least 16 weeks
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 300 mg PO twice per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
 #'''POLO:''' Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903387 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963 PubMed] NCT02184195
 ##'''Update:''' Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. [https://doi.org/10.1200/jco.21.01604 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35834777/ PubMed]
 ==Placebo==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 108: / Line 98: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Regimen_classes#Platinum-based_regimen|Platinum-based chemotherapy]] for at least 16 weeks
+</div></div>
 ===References===
 #'''POLO:''' Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903387 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963 PubMed] NCT02184195
 ##'''Update:''' Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. [https://doi.org/10.1200/jco.21.01604 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35834777/ PubMed]
 =Metastatic disease, refractory=
 ==Olaparib monotherapy {{#subobject:0c2eb3|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:21eb78|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 129: / Line 117: @@
 |-
 |}
-''Patients had germline BRCA1/2 mutations.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*Germline BRCA1/2 mutations
 ====Prior treatment criteria====
 *Gemcitabine, with progression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 400 mg PO twice per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
 <!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
 #'''Study 42:''' Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366685 PubMed] NCT01078662
 =Additional resources=
 *[https://oncomx.org/searchview/?gene=BRCA1 OncoMX -- BRCA1]
 *[https://oncomx.org/searchview/?gene=BRCA2 OncoMX -- BRCA2]
 [[Category:Pancreatic cancer regimens]]
 [[Category:Biomarker-specific pages]]
 [[Category:Gastrointestinal cancers]]

Difference between revisions of "Pancreatic cancer, BRCA-mutated"

Revision as of 12:06, 24 January 2023

Contents

Advanced or metastatic disease, first-line

Cisplatin & Gemcitabine (GC)

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Maintenance after first-line therapy

Olaparib monotherapy

Regimen

Biomarker eligibility criteria

Preceding treatment

Targeted therapy

References

Placebo

Regimen

Preceding treatment

References

Metastatic disease, refractory

Olaparib monotherapy

Regimen

Biomarker eligibility criteria

Prior treatment criteria

Targeted therapy

References

Additional resources

Navigation menu

Search