LBA74 Pembrolizumab plus chemotherapy vs chemotherapy as neoadjuvant and adjuvant therapy in locally-advanced gastric and gastroesophageal junction cancer: The phase III KEYNOTE-585 study

The phase 3 KEYNOTE-585 study (NCT03221426) evaluated neoadjuvant/adjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo in locally-advanced, resectable gastric or gastroesophageal junction (G/GEJ) cancer. A separate cohort evaluated pembro + FLOT. We report results of the pre-specified third interim analysis (IA3). Patients (pts) with untreated, locally-advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W or pbo + chemo (cisplatin + capecitabine or cisplatin + 5-FU) for 3 cycles. After surgery, pts received adjuvant pembro or pbo + chemo Q3W for 3 cycles, then adjuvant pembro or pbo Q3W for 11 cycles (main cohort). In the FLOT cohort, pts were randomized 1:1 to pembro + docetaxel, oxaliplatin, leucovorin, and 5-FU, Q2W. Primary end points were pathCR rate (BICR), EFS (RECIST 1.1, by investigator), OS (main cohort), and safety (FLOT cohort). 804 pts were randomized to the main (402 pembro; 402 pbo) and 1007 to main + FLOT ([502 pembro; 505 pbo) cohorts. Median follow-up was 47.7 mo and 46.3 mo, respectively. In the main cohort, pathCR significantly improved with pembro + chemo (12.9% [95% CI, 9.8-16.6]) vs pbo + chemo (2.0 [95% CI, 0.9-3.9]); Δ (10.9% [95% CI, 7.5-14.8]; P<0.00001). EFS was longer with pembro vs pbo (median 44.4 vs 25.3 mo; HR 0.81; 95% CI, 0.67-0.99; P=0.0198), but was not significant. OS continues to final analysis. Median OS was 60.7 vs 58.0 mo (HR 0.90; 95% CI, 0.73-1.12) at IA3. Grade ≥3 drug-related AE rates were 65% with pembro + chemo and 63% with pbo + chemo. Outcomes in the main + FLOT cohort are in the Table.Table: LBA74Outcomes in main + FLOT cohortEfficacyPembro + chemoN = 502Pbo + chemoN = 505Treatment difference (95% CI)Path CRa, %13.0 (10.2-16.3)2.4 (1.3-4.2)10.6% (7.4-14.0) P<0.0001Median EFS, mo (95% CI)45.8 (35.9-NR)25.7 (21.9-33.9)HR 0.81 (0.68-0.97) P=0.011Median OS, mo (95% CI)60.7 (51.5-NR)NR (45.7-NR)HR 0.93 (0.76-1.12)SafetyPembro + chemoN = 498Pbo + chemoN = 503NAGrade ≥ 3 drug-related AEs67%63%NAaIn first 987 pts randomized; HR, hazard ratio; NA, not applicable; NR, not reached Open table in a new tab aIn first 987 pts randomized; HR, hazard ratio; NA, not applicable; NR, not reached Neoadjuvant/adjuvant pembro + chemo followed by adjuvant pembro, significantly improved pathCR rate with no significant improvement in EFS vs placebo + chemo in pts with untreated, locally-advanced resectable G/GEJ cancer.