Joseph Chao, MD from the City of Hope speaks about the 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.
Link to Article:
https://pubmed.ncbi.nlm.nih.gov/33792646/
Abstract:
Immunotherapy has been linked to better outcomes in patients with microsatellite instability-high (MSI-H) cancers who have previously received treatment.
The goal of this study was to compare the anticancer efficacy of pembrolizumab treatment to chemotherapy in MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer patients, independent of the line of therapy they received.
Participants, setting, and design: Patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059 (third-line treatment or higher) single-arm trial, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062 (first-line treatment) randomized trials were included in this post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial Patients were enrolled in KEYNOTE-059 between March 2, 2015, and March 26, 2016, in KEYNOTE-061 between June 4, 2015, and July 26, 2016, in KEYNOTE-061, and in KEYNOTE-062 between September 18, 2015, and May 26, 2017, with data cutoff dates of August 8, 2018, October 26, 2017, and March 26, 2019, respectively.
In KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) was used; in KEYNOTE-061, pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine), or chemotherapy alone was used; and in KEYNOTE-062, pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-
Response was evaluated centrally using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and MSI-H status was verified centrally utilizing polymerase chain reaction testing.
At the data cutoff, MSI-H tumors were found in 7 of 174 patients (4.0%) in KEYNOTE-059, 27 of 514 patients (5.3%) in KEYNOTE-061, and 50 of 682 patients (7.3%) in KEYNOTE-062. In KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062, the median overall survival for individuals with MSI-H tumors was not attained (NR), and in KEYNOTE-062, the median overall survival for pembrolizumab plus chemotherapy was not reached (NR). In KEYNOTE-059, the median progression-free survival (PFS) was NR (95 percent CI, 1.1 months to NR) while in KEYNOTE-061, it was 17.8 months (95 percent CI, 2.7 months to NR) (vs 3.5 months [95 percent CI, 2.0-9.8 months] for chemotherapy). In KEYNOTE-062, pembrolizumab had a median PFS of 11.2 months (95 percent CI, 1.5 months to NR), pembrolizumab + chemotherapy had a median PFS of NR (95 percent CI, 3.6 months to NR), and chemotherapy had a median PFS of 6.6 months (95 percent CI, 4.4-8.3 months). Pembrolizumab had a 57.1 percent objective response rate (ORR) in KEYNOTE-059 and 46.7 percent (vs 16.7% for chemotherapy) in KEYNOTE-061. The ORR for pembrolizumab was 57.1 percent in KEYNOTE-062, 64.7 percent in pembrolizumab + chemotherapy, and 36.8 percent in chemotherapy.
Conclusions and Implications: The results of this study suggest that MSI-H status might be used as a biomarker for pembrolizumab therapy in patients with advanced G/GEJ cancer, independent of the line of treatment they received.
Trial registration: ClinicalTrials.gov Identifiers: NCT02335411, NCT02370498, and NCT02494583.
http://clinicaltrials.gov/show/NCT02335411