No Survival Benefit in Adding Napabucasin to Paclitaxel for Advanced Gastric, GEJ Cancers

According to results from the phase 3 BRIGHTER trial, the addition of napabucasin to paclitaxel did not improve survival for patients with pretreated, advanced gastric or gastroesophageal junction (GEJ) cancers.

The trial enrolled 714 patients with advanced gastric or GEJ cancers that did not respond to first-line therapy, who were then randomized in a 1:1 ratio to receive napabucasin plus paclitaxel (n = 357) or placebo plus paclitaxel (n = 357) from October 2, 2014, to December 12, 2016. Patients were stratified by geographic region, time-to-progression from start of first-line therapy, disease measurability, and prior use of taxane therapy.

The primary endpoint of the trial was overall survival (OS). Secondary endpoints included progression-free survival, objective response rate, disease control rate, and safety.

Based on findings from the interim analysis—wherein there was no statistically significant difference in OS between the 2 groups—the Data Safety Monitoring Board determined that there was a low probability of OS improvement, which affected the overall risk-benefit assessment. Therefore, at the recommendation of the Data Safety Monitoring Board, the BRIGHTER study was terminated on September 15, 2017.

As of the final analysis (median follow-up, 6.8 months), a total of 565 deaths had occurred. The median number of treatment cycles was 4 for both treatment arms, and OS was 6.93 months in the napabucasin group versus 7.36 months in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.86-1.20; P = .8596). This was deemed by the investigaors to not be a statistically significant difference.

In addition, no statistically significant difference was observed between the napabucasin and placebo groups for progression-free survival (3.55 vs 3.68 months, respectively), objective response rate (16% vs 18%, respectively), and disease control rate (55% vs 58%, respectively).

Grade ≥3 adverse events were reported for 69.5% patients in the napabucasin group and 59.7% of patients in the placebo group; grade ≥3 diarrhea was reported in 16.2% and 1.4% of patients, respectively.

When compared with paclitaxel monotherapy, adding napabucasin to paclitaxel for patients with second-line, advanced gastric or GEJ cancers did not improve OS, the study authors concluded.

Source:

Shah MA, Shitara K, Lordick F, et al. Randomized, double-blind, placebo-controlled phase 3 study of paclitaxel ± napabucasin in pretreated advanced gastric or gastroesophageal junction adenocarcinoma. Clin Cancer Res. Published May 31, 2022.