Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up results from CheckMate 649.
Authors: Janjigian Yelena Y. , Moehler Markus H. , Ajani Jaffer A. , Shen Lin , Garrido Marcelo , Gallardo Carlos , Wyrwicz Lucjan , Yamaguchi Kensei , Cleary James M. , Elimova Elena , Bruges Ricardo Elias , Karamouzis Michalis , Skoczylas Tomasz , Bragagnoli Arinilda , Liu Tianshu , Tehfe Mustapha , McCraith Stephen , Hu Nan , Zhang Jennifer , Shitara Kohei 
Published: January 2025

398

Background:
At 4-y follow-up, 1L NIVO + chemo continued to demonstrate clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit vs chemo with acceptable safety in patients (pts) with advanced non-HER2+ GC/GEJC/EAC from CheckMate 649. We report efficacy and safety results of NIVO + chemo vs chemo at 5-y follow-up.
Methods:
Adults with previously untreated, unresectable, advanced or metastatic, non-HER2+ GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5.
Results:
Pts were randomized to NIVO + chemo (n = 789) or chemo (n = 792). NIVO + chemo continued to show OS and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5, pts with PD-L1 CPS ≥ 1, and all randomized pts at 60-month (mo) minimum follow-up (Table). OS rates at 60-mo were higher with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5, pts with PD-L1 CPS ≥ 1, and all randomized pts (Table), and OS benefit with NIVO + chemo continued to be observed in most prespecified subgroups. Objective response rates (ORRs) were higher and responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5, pts with PD-L1 CPS ≥ 1, and all randomized pts (Table). No new safety signals were identified.
Conclusions:
These results represent the first report of 5-y follow-up for anti–PD-1 + chemo combination therapy in GC/GEJC/EAC to our knowledge. NIVO + chemo continued to provide sustained long-term survival vs chemo with an acceptable safety profile after 5 y of follow-up. These data continue to support the use of NIVO + chemo as a standard 1L treatment for advanced GC/GEJC/EAC.
Clinical trial information: NCT02872116
.

Efficacy
PD-L1 CPS ≥ 5
PD-L1 CPS ≥ 1
All randomized

NIVO + chemo(n = 473)

Chemo
(n = 482)

NIVO + chemo
(n = 641)

Chemo
(n = 656)

NIVO + chemo
(n = 789)

Chemo
(n = 792)

mOS (95% CI), mo
14.4 (13.1–16.2)
11.1 (10.1–12.1)
13.8 (12.4–14.8)
11.4 (10.7–12.3)
13.7 (12.4–14.5)
11.6 (10.9–12.5)

HR (95% CI)
0.71 (0.61–0.81)
0.76 (0.67–0.85)
0.79 (0.71–0.88)

60-mo OS rate (95% CI), %
16 (12–19)
6 (4–9)
13 (11–16)
5 (4–7)
12 (10–14)
6 (4–8)

mPFS
a
(95% CI), mo

8.3 (7.0–9.4)
6.1 (5.6–6.9)
7.5 (7.0–8.5)
6.9 (6.2–7.1)
7.8 (7.1–8.6)
6.9 (6.7–7.2)

HR (95% CI)
0.71 (0.61–0.82)
0.77 (0.68–0.87)
0.79 (0.71–0.89)

ORR
a,b
(95% CI), %

60 (55–65)
45 (40–50)
60 (55–64)
46 (42–51)
58 (54–62)
46 (42–50)

mDOR
a,c
(95% CI), mo

9.6 (8.3–12.4)
7.0 (5.7–8.0)
8.6 (7.9–10.5)
6.9 (5.8–7.6)
8.5 (7.7–9.9)
6.9 (5.9–7.6)

a
Per BICR.

b
In pts with measurable target lesions at baseline.

c
In all measurable responders.

DOR, duration of response; m, median.