Most patients with gastric cancer are diagnosed with the disease at an advanced stage. This leads to a dismal low 5-year survival rate of <10%. Fluoropyrimidine combined with a platinum agent is the standard first-line treatment for advanced gastric cancer, but even with therapy the disease will progress, necessitating further treatment. Monoclonal antibodies and taxanes have been used to treat gastric cancer as subsequent line therapies. Suitable treatment combinations have been investigated to determine if they convey survival benefits to patients with advanced gastric cancer, including an open-label, nonrandomized phase 1/2 study to evaluate the safety and efficacy of nivolumab with paclitaxel plus ramucirumab.
Eligible study patients were aged ≥20 years with an Eastern Cooperative Oncology Group performance status of 0 or 1 who were refractory to first-line chemotherapy consisting of platinum-fluoropyrimidine or who had disease recurrence >6 months after postoperative adjuvant chemotherapy. The study enrolled 43 people, with 60.5% of study participants having a PD-L1 combined positive score (CPS) ≥1. The phase 1 part of the study determined the dose-limiting toxicity and the recommended dose of nivolumab, paclitaxel, and ramucirumab. The age range of patients was 38 to 78 years, and most patients were male.
Nivolumab 3 mg/kg was administered on days 1 and 15. This was combined with paclitaxel 80 mg/m2 on days 1, 8, and 15 and ramucirumab 8 mg/kg on days 1 and 15 every 4 weeks. The median treatment duration was 4.6 months with a median follow-up of 16.8 months.
The overall response rate was 37.2% and progression-free survival was 46.5%. Overall median survival time was 13.1 months; median survival time was 13.8 months in patients with CPS ≥1 and 8 months in patients with CPS <1.
Treatment related-adverse events grade ≥3 occurred in 90.7% of patients. Immune-related adverse events grade ≥3 occurred in 32.6% of patients. The protocol treatment was discontinued in 5 patients due to toxicity. Paclitaxel-related toxicity occurred in 2 patients and 4 patients had nivolumab-related toxicities, with 1 also having toxicity due to paclitaxel.
The combination of nivolumab with paclitaxel plus ramucirumab as second-line therapy in patients with advanced gastric cancer demonstrated promising responses with manageable treatment-related adverse events.
Nakajima TE, Kadowaki S, Minashi K, et al. Multicenter phase I/II study of nivolumab combined with paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer. Clin Cancer Res. 2021;27:1029-1036.