RAINBOW-Asia underlines benefit of ramucirumab-paclitaxel for stomach cancer

The addition of the human immunoglobulin G1 monoclonal antibody ramucirumab to paclitaxel led to a significant progression-free survival (PFS) benefit in a subgroup of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have failed standard first-line chemotherapy with platinum and fluoropyrimidine (with or without anthracycline), according to the findings of the RAINBOW-Asia study, a bridging study of the RAINBOW trial, presented at ASCO GI 2021.

“The ramucirumab-paclitaxel combination as second-line therapy demonstrated a statistically significant PFS benefit and an overall survival (OS) benefit that was consistent with [the primary analysis of] RAINBOW … in a predominantly Chinese population with advanced gastric and GEJ cancer,” said the researchers.

Given the significant OS benefit observed in the primary analysis of the global phase III RAINBOW trial, this combination regimen has been approved as second-line therapy in this disease setting in around 80 countries outside China, noted the researchers.

RAINBOW-Asia looked into the efficacy and safety of the ramucirumab-paclitaxel combination regimen in an East Asian* cohort (n=440; median age 58 years, 67.8 percent male, 90 percent Chinese). Participants were randomized 2:1 to receive IV paclitaxel 80 mg/m² (days 1, 8, and 15) with either IV ramucirumab 8 mg/kg (days 1 and 15) or placebo during a 28-day cycle. [ASCO GI 2021, abstract 199]

A significant PFS benefit was observed with ramucirumab compared with placebo (median, 4.14 vs 3.15 months, hazard ratio [HR], 0.765, 95 percent confidence interval [CI], 0.613–0.955; p=0.0184). Subgroup analysis consistently favoured ramucirumab over placebo, particularly among individuals with liver metastasis (HR, 0.467) and those with ≥3 metastatic sites (HR, 0.537) and without peritoneal metastasis (HR, 0.617).

The percentage of participants having partial response was numerically greater in the ramucirumab vs the placebo arm (26 percent vs 20 percent), as was the objective response rate (26 percent vs 22 percent).

The OS benefit appears similar between the ramucirumab and the placebo arms (median, 8.71 vs 7.92 months, HR, 0.963, 95 percent CI, 0.771–1.203; p=0.7426).

“[These findings,] in combination with the [primary] results … support the efficacy of ramucirumab-paclitaxel in advanced gastric and GEJ adenocarcinoma,” said the researchers.

Regarding safety and tolerability, while there were more ramucirumab vs placebo recipients who reported grade ≥3 treatment-emergent adverse events (TEAEs; 80 percent vs 68 percent) and serious AEs (34 percent vs 26 percent), there were similar discontinuation rates due to AEs (7 percent vs 5 percent) and serious AEs (4 percent vs 3 percent). The incidence of grade ≥3 AEs of special interest was also similar between the two arms (19 percent for both).

The most common grade ≥3 TEAEs were decreased neutrophil (54 percent vs 39 percent) and white blood cell counts (43 percent vs 29 percent), followed by anaemia (16 percent vs 17 percent) and hypertension (7 percent vs 6 percent).

“Ramucirumab-paclitaxel was well-tolerated in this population, with no new safety signals observed. The safety profile of ramucirumab was consistent with previous studies,” they added.

Collectively, the efficacy and safety findings herein align with those observed in the primary RAINBOW analysis, thus reinforcing the benefit of the ramucirumab-paclitaxel combination regimen in this patient setting, they noted.