Perioperative pembrolizumab (pembro) plus chemotherapy (chemo) for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer: Asia versus non-Asia subgroup analysis of KEYNOTE-585.

Abstract

4194 Background: In the randomized phase 3 KEYNOTE-585 study (NCT03221426), pCR was significantly improved in participants (pts) with locally advanced G/GEJ cancer treated using perioperative pembro + chemo vs placebo (pbo) + chemo, although the difference in EFS did not meet the prespecified criteria for significance. We present an exploratory subgroup analysis by geographic region (Asia vs non-Asia). Methods: Eligible pts had untreated, locally advanced, resectable G/GEJ adenocarcinoma (including Siewert type 2 or 3 tumors). Pts enrolled in the main cohort (n = 804) received neoadjuvant pembro 200 mg IV Q3W or pbo + chemo (cisplatin + capecitabine or 5-FU) for 3 cycles (C); after surgery, pts received adjuvant pembro or pbo + chemo Q3W for 3C then adjuvant pembro or pbo Q3W for 11C. Pts in the FLOT cohort (n = 203) received neoadjuvant pembro 200 mg IV Q3W or pbo Q3W for 3C + FLOT Q2W for 4C; after surgery, pts received adjuvant pembro or pbo Q3W for 3C + FLOT Q2W for 4C, then adjuvant pembro or pbo Q3W for 11C. Primary end points were pCR (BICR), EFS (RECIST v1.1 by investigator), OS (main), and safety (FLOT). We report outcomes in the main and FLOT cohorts combined. The database cutoff date was February 16, 2024 (final analysis). Results: Of 1007 pts enrolled, 387 were enrolled in Asia; 620, at non-Asia sites; baseline characteristics were generally balanced, with notable exceptions for ECOG PS 1 (11.9% Asia vs 37.1% non-Asia), FLOT backbone (1.6% vs 31.8%), tumor location stomach (86.6% vs 68.9%), and tumor stage III-IVa (85.8% vs 74.0%). In the Asia subgroup, pCR was 17.1% with pembro + chemo vs 2.1% with pbo + chemo (difference, 15.0%; 95% CI, 9.7-21.2); median EFS was 69.8 mo vs 42.7 mo (HR, 0.81; 95% CI, 0.60-1.10), with a 5-year rate of 54.1% vs 45.6%; median OS was not reached (NR) vs NR (HR, 0.87; 95% CI, 0.63-1.19), with a 5-year rate of 61.3% vs 57.4%. In the non-Asia subgroup, pCR was 12.4% with pembro + chemo vs 3.3% with pbo + chemo (difference, 9.1%; 95% CI, 4.9-13.6); median EFS was 37.7 mo vs 24.3 mo (HR, 0.79; 95% CI, 0.64-0.98), with a 5-year rate of 44.0% vs 33.0%; median OS was 60.7 mo vs 42.4 (HR, 0.85; 95% CI, 0.68-1.06), with a 5-year rate of 50.5% vs 42.6%. In the Asia subgroup, treatment-related AE (TRAE) rates were 98.4% with pembro + chemo vs 97.4% with pbo + chemo; grade 3-5 TRAE rates were 69.6% vs 65.1%, respectively. In the non-Asia subgroup, TRAE rates were 94.1% with pembro + chemo vs 96.1% with pbo + chemo; grade 3-5 TRAE rates were 65.5% vs 61.7%, respectively. Conclusions: A favorable trend in EFS and OS was seen in both the Asia and the non-Asia subgroups of KENOTE-585; additional antitumor activity of pembro + chemo was consistently observed, regardless of region. The safety profiles were generally comparable between the subgroups. These findings support the global development of this perioperative immunotherapy/chemotherapy regimen. Clinical trial information: NCT03221426 .