MSI-H or dMMR

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1 regimens on this page
3 variants on this page


Note: this is a new type of page for HemOnc.org, as all other regimen pages (except for cancer of unknown primary) are tissue-specific. The initial drug with tissue-agnostic approval is for patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

All lines of therapy

Pembrolizumab monotherapy

Variant #1, q2wk dosing

Study Evidence
Le et al. 2017 (KEYNOTE-016) Phase II

Note: this was an expansion to a CRC-specific trial.

Immunotherapy

14-day cycles

Variant #2, q3wk, adult dosing

FDA-recommended dose
Study Evidence
Le et al. 2016 (KEYNOTE-164) Phase II
Schellens et al. 2017 (KEYNOTE-158) Phase II

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.

Immunotherapy

21-day cycle for up to 2 years

Variant #3, q3wk, pediatric dosing

FDA-recommended dose
Study Evidence
Le et al. 2016 (KEYNOTE-164) Phase II
Schellens et al. 2017 (KEYNOTE-158) Phase II

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.

Immunotherapy

21-day cycle for up to 2 years

References

  1. Abstract: Dung T. Le, Takayuki Yoshino, Dirk J├Ąger, 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
  2. Abstract: Jan H.M. Schellens, Aurelien Marabelle, Susan Zeigenfuss, Jie Ding, Scott Knowles Pruitt, and Hyun Cheol Chung. Pembrolizumab for previously treated advanced cervical squamous cell cancer: Preliminary results from the phase 2 KEYNOTE-158 study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 5514-5514. link to abstract
  3. KEYNOTE-016: 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