Nivolumab plus chemotherapy: new standard for first-line treatment of gastric cancer?

Both CheckMate-649 and ATTRACTION-4 showed a statistically significant improvement in progression-free survival (PFS) for nivolumab-based first-line treatment of advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/oesophageal adenocarcinoma (EAC)

In recent years, nivolumab provided superior overall survival (OS) in heavily pretreated patients with GC/GEJC [1]. In addition, first-line treatment with nivolumab plus chemotherapy showed promising results in a phase 2 trial in patients with advanced/recurrent GC/GEJC [2].

In CheckMate 649, 1,581 patients were 1:1 randomised to receive either nivolumab (240 mg) plus chemotherapy (FOLFOX every 2 weeks or XELOX every 3 weeks) or chemotherapy alone. In patients with positive PD-L1 tumour expression (CPS ≥5) both PFS and OS were significantly improved in the nivolumab plus chemotherapy-arm versus chemotherapy alone [3]. Median OS was 14.4 versus 11.1 months (HR 0.71; P<0.0001) and OS rate at 12 months was 57% and 46%, respectively. Superior OS benefit for nivolumab plus chemotherapy was also seen in patients with PD-L1 CPS ≥1 (HR 0.77) and in all randomised patients (irrespective of PD-L1 expression; HR 0.80; see Figure).

In the phase 3 part of the ATTRACTION-4 trial, 724 Asian GC/GEJC/EAC patients were 1:1 randomised to receive nivolumab plus chemotherapy (CAPOX or oxaliplatin/S1) or chemotherapy alone [4]. Median PFS was significantly improved in the nivolumab plus chemotherapy-arm (10.5 vs 8.4 months; HR 0.68; P=0.0007). However, after a median follow-up of 26.6 month, there was no statistically significant difference in median OS (17.5 vs 17.3 months; HR 0.90; P=0.257).

Figure: Overall survival in all randomised patients of phase 3 CheckMate 649 trial [3]

1. Kang Y-K, et al. 2017;390:2461-2471.
2. Boku N, et al. Ann Oncol. 2019;30:250-258.
3. Möhler M, et al. Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. ESMO 2020 Virtual Meeting, abstract LBA6.
4. Boku N, et al. Nivolumab plus chemotherapy versus chemotherapy alone in patients with previously untreated advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer: ATTRACTION-4 (ONO-4538-37) study. ESMO 2020 Virtual Meeting, abstract LBA7.

Posted on 25 November 202021 May 2024