Multinational phase 3 trial of first-line capivasertib plus paclitaxel for metastatic triple-negative breast cancer

The multinational phase 3 CAPItello-290 trial evaluated first-line capiversatib (pan-AKT inhibitor) plus paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC), including in the subgroup of patients with PIK3CA/AKT1/PTEN-altered tumors. A total of 812 patients with previously untreated mTNBC (30.7% with PIK3CA/AKT1/PTEN-altered tumors) were randomized 1:1 to paclitaxel plus capivasertib or paclitaxel plus placebo. Among all patients, median overall survival was 17.7 months with capivasertib plus paclitaxel versus 18.0 months with placebo-paclitaxel (p=0.3239); among patients with with PIK3CA/AKT1/PTEN-altered tumors, median OS was 20.4 months in both arms (p=0.7602). Median progression-free survival in the overall population numerically favored capivasertib plus paclitaxel over placebo plus paclitaxel (5.6 versus 5.1 months; HR 0.72; 95% CI 0.61-0.84); this was also the case in patients with PIK3CA/AKT1/PTEN-altered tumors (7.5 months versus 5.6 months; HR 0.70; 95% CI 0.52-0.95). The most frequent grade ≥ 3 adverse event was diarrhea (12.7% versus 0.7% with placebo-paclitaxel in the overall population); capivasertib was discontinued due to AEs in 8.5% of patients. AEs led to death in 4.2% of patients. The authors conclude that capivasertib-paclitaxel did not meet the prespecified boundary for improving OS in either population.