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Association details:
| Biomarker: | MSI-H/dMMR |
|---|---|
| Cancer: | Gastric Cancer |
| Drug: | Keytruda (pembrolizumab) (PD1 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) for Patients With Microsatellite Instability-High (MSI-H) or Deficient Mismatch Repair (dMMR) Tumors in Five Different Types of Cancer
Published date:
04/29/2022
Excerpt:
Merck...announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with...unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy.
Source:
Title:
Pembrolizumab for previously treated endometrial, biliary, colorectal, gastric or small intestine cancer with high microsatellite instability or mismatch repair deficiency
Published date:
09/20/2023
Excerpt:
Pembrolizumab is recommended as an option for treating tumours with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency in adults with…unresectable or metastatic gastric, small intestine or biliary cancer that has progressed during or after 1 therapy
Source:
Published date:
08/29/2023
Excerpt:
Gastric Cancer: Preferred Regimens...MSI-H/dMMR tumors…Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and pembrolizumab…
Secondary therapy:
5-fluorouracil + oxaliplatin; capecitabine + oxaliplatin
Source:
Excerpt:
Preferred Regimens: Pembrolizumab for second-line or subsequent therapy for MSI-H or dMMR tumors
Source:
Title:
Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials
Published date:
04/01/2021
Excerpt:
Pembrolizumab monotherapy in KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) in KEYNOTE-061, and pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine)...In KEYNOTE-062, the ORR was 57.1% for pembrolizumab , 64.7% for pembrolizumab plus chemotherapy, and 36.8% for chemotherapy....MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer...
Secondary therapy:
bisphosphonate bound paclitaxel; CF; XP
DOI:
10.1001/jamaoncol.2021.0275
Trial ID:
Source:
Title:
JZP898 Intravenous Infusion as Monotherapy and Combination With Pembrolizumab in Adults With Advanced/Metastatic Solid Tumors
Excerpt:
...Previously treated participants with solid tumors (NSCLC, melanoma, HNSCC, RCC, HCC, gastroesophageal carcinomas, UC, or CRC [MSI-H]) for whom, in the opinion of the investigator, there is...
Trial ID:
Source:
Title:
A Study to Evaluate the Safety and the Activity of S095029 as Part of Combination Therapy in Advanced Gastroesophageal Junction/Gastric Cancers.
Excerpt:
...- Participants' tumor must have an MSI-H or dMMR status according to institutional guidelines and/or according to the College of American Pathologists, determined at any time prior to enrolment....
Trial ID:
More C2 evidence
Source:
Title:
Exploratory Single-arm, Single-center Adjuvant Treatment of Stage IIIB-IIIC Gastric Cancer With Combination of Palizumab and SOX Regimen
Excerpt:
...Consistent with high-frequency microsatellite instability MSI-H 2....
Trial ID:
Source:
Title:
LITT and Pembrolizumab in Recurrent Brain Metastasis
Excerpt:
...Microsatellite Instability-High Cancer 9....
Source:
Title:
Study of Pembrolizumab in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine: Integration of Molecular Subtypes Through Integrative Genomic Analysis
Excerpt:
...(Only Cohort B) confirmed as MSI-H via the PCR or IHC staining by institutional standard....
Trial ID:
Source:
Title:
Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers
Excerpt:
...- Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2)....
Trial ID:
Less C2 evidence
Source:
Title:
Comparison of efficacy between immune checkpoint inhibitors and irinotecan-based chemotherapy as third-line treatment for patients with advanced gastric cancer: A Korean real-world multicenter study (KCSG ST22-06).
Published date:
05/25/2023
Excerpt:
We retrospectively reviewed patients with RMGC, whose third-line treatment started between July 2019 and June 2021 at 17 centers in South Korea. The ICI group included patients who received nivolumab or pembrolizumab...microsatellite instability-high (MSI-H)/mismatch repair-deficient (MMR-D) tumor was an independent prognostic factor for superior OS. The ICI group showed significantly longer OS than the irinotecan-based chemotherapy group in patients without peritoneal metastasis [HR 0.54 (95% CI 0.30-0.99); P=0.047)].
DOI:
10.1200/JCO.2023.41.16_suppl.e16047
Source:
Title:
Preoperative pembrolizumab for MSI high, EBV positive or PD-L1 positive locally advanced gastric cancer followed by surgery and adjuvant chemoradiation with pembrolizumab: Interim results of a phase 2 multi-center trial
Published date:
05/25/2023
Excerpt:
Of the 33 patients, 12 were MSI-H, 3 EBV (+), and 27 had PDL1 expression with CPS >/= 1%. Tumors were of advanced clinical stage with 84.8% ≥ cT3 and 57.6% cN(+). All patients received two cycles of neoadjuvant pembrolizumab...treatment effect was seen in 46%, down-staging in 50%, and complete pathologic response seen in 3 patients, 2 of whom has MSI-H tumors and one whose tumor was PDL1+...This study presents a novel and effective paradigm for the management of localized gastric cancer...
Secondary therapy:
capecitabine
DOI:
10.1200/JCO.2023.41.16_suppl.e16073
Trial ID:
Source:
Title:
Pembrolizumab in Microsatellite Instability High or Mismatch Repair Deficient Cancers: Updated Analysis from the Phase 2 KEYNOTE-158 Study
Published date:
06/06/2022
Excerpt:
Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%)...ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cutoff date) was 30.8% (95% CI, 25.8‒36.2). Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months). Median progression-free survival was 3.5 months (95% CI, 2.3‒4.2 months) and median overall survival was 20.1 months (95% CI, 14.1‒27.1 months)...Pembrolizumab demonstrated clinically meaningful and durable benefit, with high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.
DOI:
10.1016/j.annonc.2022.05.519
Trial ID:
Source:
Title:
Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) for Patients With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors in Five Different Types of Cancer
Published date:
03/25/2022
Excerpt:
...Merck...today announced the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of the following microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer who have disease progression on or following at least one prior therapy....The CHMP’s recommendation was based on results from the Phase 2 KEYNOTE-158 trial as well as results from the Phase 2 KEYNOTE-164 trial...
Source:
Title:
Preoperative pembrolizumab for MSI high, EBV positive or PD-L1 positive locally advanced gastric cancer followed by surgery and adjuvant chemoradiation with pembrolizumab: Interim results of a phase 2 multi-center trial (NCT03257163).
Published date:
05/19/2021
Excerpt:
Early results from our phase 2 clinical trial show immunotherapy to be well tolerated with limited toxicity...Following 2 cycles of pembrolizumab, 2 patients with MSI-H had complete pathologic response.
Trial ID:
Source:
Title:
Matched therapies for advanced gastric cancer based on genotype: A real-world study in China.
Published date:
05/19/2021
Excerpt:
...6 (20%) dMMR/MSI-H/TMB-H (received sintilimab, pembrolizumab, tislelizumab or nivolumab, combined with antivascular or not, cohort C)...In cohort C, ORR was 17% (1/6), DCR was 67% (4/6), mPFS and mOS was 1.9 months and 6.8 months, respectively.
Source:
Title:
Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability–High Gastric Cancer
Published date:
04/21/2021
Excerpt:
We conducted a phase II trial of pembrolizumab in patients with advanced MSI-H gastric cancer and included serial...nonsynonymous mutations correlated with antitumor activity and prolonged progression-free survival (PFS...MSI-H gastric cancer and may inform development of strategies to enhance responsiveness.
DOI:
10.1158/2159-8290.CD-21-0219
Source:
Title:
Pembrolizumab (pembro) in microsatellite instability-high (MSI-H) advanced gastric/gastroesophageal junction (G/GEJ) cancer by line of therapy.
Published date:
01/23/2020
Excerpt:
In pts with MSI-H tumors, OS and PFS were prolonged with pembro vs chemo, with higher ORR (Table).
Source:
Title:
Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study
Published date:
11/04/2019
Excerpt:
Our study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Median progression-free survival and median overall survival for the seven largest tumor cohorts are summarized in Table 3.
DOI:
10.1200/JCO.19.02105
Trial ID:
