Atezolizumab in early-relapsing mTNBC did not show a statistically significant improvement in PFS or OS

IMpassion132 double-blind randomized phase 3 trial of chemotherapy (CT) ± atezolizumab (atezo) for early-relapsing unresectable locally advanced or metastatic triple-negative breast cancer (aTNBC) - (Abstract #180O; Dent et al.)  

Data from the P3 IMpassion132 trial of atezolizumab (anti-PD-L1) in early-relapsing mTNBC did not show a statistically significant improvement in PFS or OS for atezolizumab + chemotherapy versus chemotherapy alone;

• Assessment
  • The P3 IMPassion132 trial failed to show a statistically significant improvement in PFS or OS for atezolizumab + chemotherapy vs chemotherapy alone in both PD-L1+ and all-comer early relapsing TNBC populations
    • mOS (12.1mo vs 11.2mo, HR: 0.93 for PL-L1+; 10.4mo vs 9.8mo, HR: 0.94 for mITT) is consistent with RWE data in this population
    • No new safety signals were identified
    • It was highlighted that there is a high unmet need in early relapsing TNBC, despite fewer patients at this stage
  • Despite regulatory submission guided for 2024, filing is unlikely given the negative data
    • atezolizumab is currently approved in the EU for 1L PD-L1+ TNBC only in combination with nab-paclitaxel based on Phase 3 IMpassion130; in the US, Roche withdrew its AA in 1L TNBC after Phase 3 IMpassion131 (+ pac) failed to meet its primary endpoint
    • Negative data from IMpassion132 as well its history of other failures in this space may further reinforce HCPs’ existing concerns about atezolizumab, potentially creating a negative halo effect
  • Study Information
    • IMpassion132 (NCT03371017): P3, atezolizumab + chemo (capecitabine or carboplatin/gemcitabine) vs placebo + chemo, 1L early-relapsing TNBC
      • N=177 vs 177 (PD-L1+), 192 vs 188 (modified ITT) 
      • 1EP: OS in PD-L1+ and mITT  
      • Key 2EP: PFS, ORR, safety 
      • mFU: 9.8mo 
    • Efficacy (atezolizumab + chemo vs placebo + chemo)
      • PD-L1+ TNBC:
        • mOS: 12.1mo vs 11.2mo (HR: 0.93; p=0.59)
        • mPFS: 4.2mo vs 3.6mo (HR: 0.84)
        • Unconfirmed ORR: 40% vs 28%
      • mITT:
        • mOS: 10.4mo vs 9.8mo (HR: 0.94)
        • mPFS: 3.7mo vs 3.6mo (HR: 0.96)
        • Unconfirmed ORR: 31% vs 32%
      • Safety (atezolizumab + chemo vs placebo + chemo)
        • AEs: 96% vs 96%
          • Gr3/4: 67% vs 71%
          • Gr5: 1% vs 1%
        • TRAEs: 90% vs 91%
          • Gr3/4: 62% vs 65%
          • Gr5: <1% vs 1%