Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer

Abstract

We conducted a phase I/II study to investigate the safety and efficacy of nivolumab (NIVO) with paclitaxel (PTX) plus ramucirumab (RAM). Experimental Design: Patients with advanced gastric cancer (AGC) refractory to first-line chemotherapy were included. Patients received NIVO (3 mg/kg on days 1 and 15) combined with PTX (80 mg/m2 on days 1, 8, and 15) and RAM (8 mg/kg on days 1 and 15) every 4 weeks. After feasibility evaluation in 6 patients (phase I), 37 additional patients were enrolled to the phase II with the primary endpoint of 6-month progression-free survival (PFS) rate with two-sided 80% CI. The combined positive score (CPS) was defined as the number of programmed death-ligand 1-positive cells divided by the total number of viable tumor cells, multiplied by 100. Results: Forty-three patients were enrolled. Of these, 60.5% had CPS≥1. Dose-limiting toxicities were observed in 2 patients, and the recommended dose was determined as level 1. Thirty-nine (90.7%) patients experienced treatment-related adverse events ≥ grade 3 and 14 (32.6%) patients experienced immune-related adverse events ≥ grade 3. The overall response rate was 37.2% (95%CI, 23.0%-53.5%) and the 6-month PFS rate was 46.5% (80% CI, 36.4%-55.8%) (P=0.067). Median survival time was 13.1 months Research.

Rapidly Evolving Treatment Landscape for Metastatic Esophagogastric Carcinoma: Review of Recent Data

“…68 A recent small single-arm phase I/II study by Nakajima et al explored the role of concurrent PD-1 and VEGFR2 inhibition as second-line treatment for advanced GC. 69 It demonstrated manageable toxicities and promising antitumor activity of nivolumab combined with paclitaxel plus ramucirumab with ORR and 6-month PFS rate of 37.2% (95% CI, 23.0-53.5%) and 46.5% (80% CI, 36.4%-55.8%; p = 0.067), respectively. Median OS was 13.1 mos (95% CI, 8.0-16.6 mos) with the most survival benefit observed in patients whose tumor had a PD-L1 CPS ≥ 1 (mOS 13.8 mos [95% CI, 8.0-19.5]), compared to those with PD-L1 CPS < 1 (mOS 8.0 mos [95% CI, 4.8-24.1]).…”

Durable Clinical Response to Immune and Targeted Therapies in an Elderly Man with Synchronous Gastric (HER2+) and Bladder Cancers: Case Report and Literature Review

“…The introduction of immune checkpoint inhibitors (ICIs) during recent years has brought improvements in treating advanced gastric and bladder cancers. [18][19][20] However, research is lacking on efficacy/safety aspects of ICI use for MPMTs; and despite the proven efficacy of monotherapy trastuzumab and ICIs in patients with HER2+ gastric cancer, we have seen little reporting of related efficacy and safety of the combination use. Also, the long-term survival benefit of this strategy remains unclear.…”

Comparison of Efficacy and Safety of Third-Line Treatments for Advanced Gastric Cancer: A Systematic Review With Bayesian Network Meta-Analysis

“…Therefore, early detection, early diagnosis, and early treatment not even greatly improved the cure rate of GC but also enriched the choices of efficient subsequent treatment after recurrence, which would further prolong the survival of patients (42). In addition to TAS-102 and ICI monotherapy, the combination of ICI and anti-angiogenic agent in AGC has recently shown good prospect in multiple small-sized clinical studies (43)(44)(45)(46)(47)(48). Small molecular VEGFR TKI lenvatinib in combination with anti-PD-1 antibody pembrolizumab achieved a satisfying ORR of 69% and mPFS of 7.1 months in the first-line or second-line treatment of GC as revealed in the phase 2 EPOC1706 study (43).…”