Difference between revisions of "Malignant solid neoplasm, MSI-H or dMMR"
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+ | =Guidelines= | ||
+ | ==JSCO/ESMO/ASCO/JSMO/TOS== | ||
+ | *'''2020:''' Yoshino et al. [https://doi.org/10.1016/j.annonc.2020.03.299 JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions] | ||
=All lines of therapy= | =All lines of therapy= |
Revision as of 23:29, 6 November 2020
4 regimens on this page
6 variants on this page
|
Guidelines
JSCO/ESMO/ASCO/JSMO/TOS
- 2020: Yoshino et al. JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions
All lines of therapy
Pembrolizumab monotherapy
Regimen variant #1, q2wk dosing
Study | Years of enrollment | Evidence |
---|---|---|
Le et al. 2015 (KEYNOTE-016) | 2013-2015 | Phase II (RT) |
Note: this was an expansion to a CRC-specific trial.
Biomarker eligibility criteria
- Protein: MMR
- Alteration: dMMR
Immunotherapy
- Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1
14-day cycles
Regimen variant #2, q3wk, adult dosing
FDA-recommended dose |
Study | Evidence |
---|---|
Le et al. 2016 (KEYNOTE-164) | Phase II (RT) |
Marabelle et al. 2019 (KEYNOTE-158) | Phase II (RT) |
Note: this is the FDA-approved adult pembrolizumab dose and schedule based on a pooled analysis of 5 non-randomized trials, of which two were prospective: KEYNOTE-158 and KEYNOTE-164.
Biomarker eligibility criteria
- KEYNOTE-164
- Protein: MMR
- Alteration: dMMR
- Acceptable methods of measurement: IHC
- KEYNOTE-158
- Protein: PD-L1
- Alteration: expression
- Acceptable methods of measurement: IHC
Preceding treatment
- KEYNOTE-164: prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and, if KRAS and NRAS wild type, cetuximab or panitumumab; no prior anti-cancer therapy within last 2 weeks
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV over 30 minutes once on day 1
21-day cycle for up to 35 cycles (2 years)
Regimen variant #3, q3wk, pediatric dosing
FDA-recommended dose |
Study | Evidence |
---|---|
Le et al. 2016 (KEYNOTE-164) | Phase II (RT) |
Marabelle et al. 2019 (KEYNOTE-158) | Phase II (RT) |
Note: this is the FDA-approved pediatric pembrolizumab dose and schedule based on a pooled analysis of 5 non-randomized trials, of which two were prospective: KEYNOTE-158 and KEYNOTE-164.
Biomarker eligibility criteria
- KEYNOTE-164
- Protein: MMR
- Alteration: dMMR
- Acceptable methods of measurement: IHC
- KEYNOTE-158
- Protein: PD-L1
- Alteration: expression
- Acceptable methods of measurement: IHC
Preceding treatment
- KEYNOTE-164: prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and, if KRAS and NRAS wild type, cetuximab or panitumumab; no prior anti-cancer therapy within last 2 weeks
Immunotherapy
- Pembrolizumab (Keytruda) 2 mg/kg (maximum dose of 200 mg) IV over 30 minutes once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- 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 abstract TPS787 and abstract TPS3631; NCT02460198 at ClinicalTrials.gov
- 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 protocol link to PMC article 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. link to original article link to PMC article contains verified protocol in supplement PubMed
- KEYNOTE-158: Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10. Epub 2019 Nov 4. link to original article PubMed NCT02628067