Impact of Nivolumab Plus Chemotherapy on Conversion Therapy in Clinical Stage IVB HER2-negative Gastric Cancer.

Objective: The approval of first-line nivolumab plus chemotherapy marks a breakthrough in treating human epidermal growth factor receptor 2 (HER2)-negative unresectable advanced gastric and gastroesophageal junction (G/GEJ) cancer. This study aimed to evaluate the impact of nivolumab plus chemotherapy on conversion therapy in clinical stage (cStage) IVB HER2-negative G/GEJ adenocarcinoma.

Methods: Patients with cStage IVB HER2-negative G/GEJ adenocarcinoma who underwent systemic chemotherapy at Hyogo Medical University Hospital from January 2017 to March 2023 were included. Nivolumab plus chemotherapy was initiated following its approval in Japan in November 2021. Conversion surgery (CS) was performed when distant metastases had disappeared, except for resectable liver metastases.

Results: In total, 103 patients were eligible: 28 received nivolumab plus chemotherapy, and 75 received chemotherapy as first-line treatment. The conversion rate in the nivolumab plus chemotherapy group was significantly higher than that in the chemotherapy group (28.6% vs. 8.0%, p=0.011). Multivariate analysis revealed a significant association between first-line nivolumab plus chemotherapy and undergoing CS [odds ratio=3.540, 95% confidence interval (CI)=1.059-12.157]. R0 resection was achieved in all eight patients who underwent CS, and delayed immune-related adverse events did not occur perioperatively. In the nivolumab plus chemotherapy group, the median survival time in patients who underwent CS was significantly longer than that in patients treated with chemotherapy alone [not reached (95%CI=22.7-not reached) vs. 11.8 months (95%CI=5.1-33.3), p=0.035].

Conclusions: First-line nivolumab plus chemotherapy increased the conversion rate compared with chemotherapy in patients with cStage IVB HER2-negative G/GEJ adenocarcinoma. CS following nivolumab plus chemotherapy was safe, and patients who underwent CS survived longer than those who received chemotherapy alone.