capivasertib + paclitaxel vs. placebo + paclitaxel in 1L mTNBC failed to meet the dual OS primary endpoint in the all-comer population

Capivasertib (C) + paclitaxel (P) as first-line treatment of metastatic triple-negative breast cancer (mTNBC): the CAPItello-290 Phase 3 trial
(Abstract LBA19; McArthur et al.)   

The P3 CAPItello-290 trial of capivasertib + paclitaxel vs. placebo + paclitaxel in 1L mTNBC failed to meet the dual OS primary endpoint in the all-comer population and the PIK3CA/AKT1/PTEN-altered population; With this, capivasertib is no longer a competitive threat in 1L TNBC to Trodelvy as AZ will no longer pursue development in this space.

• Key Takeaways  
  • As previously announced by AstraZeneca, the Phase 3 CAPItello-290 trial evaluating capivasertib + paclitaxel vs placebo + paclitaxel in 1L mTNBC did not meet its dual primary endpoints of OS in both all-comer and biomarker-confined populations
    • The PFS numerically favored capivasertib + paclitaxel over placebo and the safety profile of the combination was broadly consistent with previous data
  • With its failure, CAPItello-290 is no longer a potential threat to expansion into 1L TNBC  
    • Capivasertib + fulvestrant has been approved by the FDA and EMA for 1L+ PIKCA/AKT1/PTEN-altered, HR+/HER2- mBC post-ET though the threat is indirect given the biomarker restricted approval and earlier line of therapy
  • The discussant commented that while the CAPItello-290 trial failed to meet its primary endpoint, the numerical PFS and ORR benefit could suggest that further analysis is required; While the discussant believed that TNBC should be further stratified to select a more sensitive group the speaker disclosed that AstraZeneca will no longer pursue capivasertib in TNBC
• Study Information
  • CAPItello-290 (NCT03997123): P3, capivasertib + paclitaxel vs placebo + paclitaxel, 1L TNBC
  • N = 812 (404 vs 408)
    • PIK3CA/AKT1/PTEN-altered tumors: 249 (124 vs 125)
  • 1EP: OS (ITT & PIK3CA/AKT1/PTENmut)
  • 2EP: PFS, ORR, AEs, DOR, CBR, QoL, PK/PD
• Efficacy (paclitaxel + paclitaxel vs placebo + paclitaxel)
  • Overall population
    • mOS (mos): 17.7 vs 18.0 (HR: 0.92)
    • mPFS (mos): 5.6 vs 5.1 (HR: 0.72)
    • ORR: 50% vs 38%
  • PIK3CA/AKT1/PTENmut population
    • mOS (mos): 20.4 vs 20.4 (HR: 1.05)
    • mPFS (mos): 7.5 vs 5.6 (HR: 0.70)
    • ORR: 54% vs 42%
• Safety (capivasertib + paclitaxel vs placebo + paclitaxel)
  • Any AEs: 98% vs 95%
    • Most common were diarrhea (75% vs 26%) and anemia (39% vs 31%)
  • Gr3+ AEs: 58% vs 39%
    • Most common Gr3+ AEs were diarrhea (13% vs 1%) and neutropenia (7% vs 7%)
    • SAEs: 25% vs 17%
    • AEs leading to death: 5% vs 3%