Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥10

• Published in: Clinical cancer research 2021-04, Vol.27 (7), p.1923-1931
• Main Authors: Wainberg, Zev A, Fuchs, Charles S, Tabernero, Josep, Shitara, Kohei, Muro, Kei, Van Cutsem, Eric, Bang, Yung-Jue, Chung, Hyun Cheol, Yamaguchi, Kensei, Varga, Eniko, Chen, Jen-Shi, Hochhauser, Daniel, Thuss-Patience, Peter, Al-Batran, Salah-Eddin, Garrido, Marcelo, Kher, Uma, Shih, Chie-Schin, Shah, Sukrut, Bhagia, Pooja, Chao, Joseph
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - therapeutic use; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - mortality; Esophagogastric Junction; Female; Humans; Immune Checkpoint Inhibitors - therapeutic use; Male; Middle Aged; Stomach Neoplasms - drug therapy; Stomach Neoplasms - mortality
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-20-2980

Pembrolizumab demonstrated efficacy in PD-L1-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS ≥ 10 in these trials. Included were patients with CPS ≥ 10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, = 46; ), KEYNOTE-061 (pembrolizumab, = 53; chemotherapy, = 55; ), and KEYNOTE-062 (pembrolizumab, = 92; chemotherapy, = 90; primary). Efficacy outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). In KEYNOTE-059, median follow-up was 6 months, median OS was 8 months [95% confidence interval (CI), 5.8-11.1], ORR was 17%, and median (range) DOR was 21 months (3+ to 35+). In KEYNOTE-061, median follow-up was 9 months, median OS (pembrolizumab vs. chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41-1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56-1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4 to 26+ months) versus 7 months (3-7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49-0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79-1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+). This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer.