A randomized phase II trial of paclitaxel plus ramucirumab versus nab-paclitaxel plus ramucirumab for gastric cancer with peritoneal dissemination refractory to first-line therapy (WJOG10617G/P-SELECT).
Authors: Kenro Hirata, Yasuo Hamamoto, Hirokazu Shoji, Hiroki Hara, Chihiro Kondoh, Hisateru Yasui, Takeshi Kajiwara, Eishi Baba, Takayuki Ando, Naotoshi Sugimoto, Naohiro Okano, Hisato Kawakami, Hiroo Katsuya, Michitaka Nagase, Toshikazu Moriwaki, Kenichi Yoshimura, Masahiko Ando, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro
Journal: Journal of Clinical Oncology (2022)

280 Background: Combination of ramucirumab (RAM) + weekly paclitaxel (PTX) is recommended as a standard second-line therapy for unresectable or recurrent gastric cancer (GC). A recent phase II trial evaluating nab-PTX and RAM combination showed that nab-PTX+RAM is promising efficacy and tolerability as well as PTX+RAM. In subgroup analysis of another phase III trial (ABSOLUTE) comparing different nab-PTX scheduling with PTX, weekly nab-PTX was especially effective for the patients with peritoneal dissemination compared to PTX without RAM combination. Therefore, we hypothesized that nab-PTX+RAM would be more effective than PTX+RAM for patients with peritoneal dissemination. Methods: The P-SELECT trial (WJOG10617G) is an open-label randomized phase II study evaluating the safety and efficacy of PTX+RAM and nab-PTX+RAM in GC patients with peritoneal metastasis. Key eligibility criteria were: 1) histologically proven adenocarcinoma, 2) unresectable or recurrent gastric cancer, 3) peritoneal dissemination, 4) intolerance or refractory to first-line therapy including fluoropyrimidines, 5) PS 0–2. Peritoneal dissemination was confirmed by either contrast enema/enterography, CT scan, clinical signs, or operative findings (including exploratory laparoscopy). The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), ascites control rate, safety, and neuropathy-specific quality of life. 105 subjects were required to maintain the power of ≥70% expecting the hazard ratio (HR) of 0.90 in OS. The study was conducted in 58 centers of the West Japan Oncology Group. Results: A total of 105 patients (median age 67; M:F 66:39) were randomized (53 patients in PTX+RAM and 52 in nab-PTX+RAM). Moderate and massive amount of ascites was observed in 39.0% of patients. Median OS was 8.1 months in PTX+RAM and 7.2 months in nab-PTX+RAM (HR 1.04, 95% confidence interval [CI] 0.67–1.61, P = 0.63). Median PFS was 5.1 months in PTX+RAM and 3.9 months in nab-PTX+RAM (HR 1.04, 95% CI 0.69–1.56, P = 0.89). The ORR and DCR for PTX+RAM and nab-PTX+RAM were 20.7% vs. 20.0% (P = 0.99) and 77.4% vs. 63.5% (P = 0.15), respectively. The ascites control rate was 86.1% in PTX+RAM and 70.3% in nab-PTX+RAM (P = 0.07). The incidence of grade 3/4 neuropathy was higher in nab-PTX+RAM (7.5% vs 17.6%, P = 0.14), whereas there was no difference in neuropathy-specific quality of life between the two groups. The incidence of febrile neutropenia was higher in PTX+RAM (11.3% vs 5.9%, P = 0.49). Conclusions: The potential difference in efficacies between nab-PTX+RAM and PTX+RAM was not shown in advanced gastric cancer with peritoneal dissemination. The results of the pre-planned translational research will be available soon. Clinical trial information: jRCTs031180022.