• Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first- line paclitaxel (PAC) +/- atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC)

      Miles, D. W.; Gligorov, J.; Andre, F.; Cameron, D.; Schneeweiss, A.; Barrios, C. H.; Xu, B.; Wardley, Andrew M; Kaen, D.; Andrade, L.; et al. (2020)
      Background: In the phase 3 IMpassion130 trial, combining atezo with first-line nabpaclitaxel for mTNBC showed significantly improved progression-free survival (PFS) and clinically meaningful overall survival (OS) benefit in patients with PD-L1+ mTNBC [Schmid NEJM 2018]. IMpassion131 (NCT03125902) evaluated atezo + PAC as firstline treatment for mTNBC. Methods: Eligible patients (no prior systemic therapy or ≥12 months since [neo] adjuvant chemotherapy) were randomised 2:1 to atezo 840 mg or placebo (d 1 & 15 q28d), both with PAC 90 mg/m2 (d 1, 8 & 15 q28d) until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status (immune cell [IC] expression <1% vs 1% by VENTANA SP142 assay), prior taxane, liver metastases and geographic region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1+ (IC 1%) population, then in the intent-to-treat (ITT) population. OS and overall response rate (ORR) were secondary endpoints. Results: Of 651 randomised patients, 45% had PD-L1+ mTNBC, 48% were taxane pretreated, 31% had de novo mTNBC and 27% liver metastases. Adding atezo to PAC did not improve PFS or OS in either the PD-L1+ or ITT populations (Table). PFS results in subgroups were consistent with primary results. PAC exposure was not compromised by the addition of atezo. Grade 5 (2% placebo vs 2% atezo) and grade 3/4 AEs (43% vs 49%) were balanced between arms and the safety profile was consistent with known risks of each study drug. Conclusions: Atezo + PAC did not improve PFS or OS vs placebo + PAC. No new safety signals were seen. Potential reasons for the contrast with the benefit seen in IMpassion130 (atezo + nab-paclitaxel) need further exploration.
    • Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

      Miles, D.; Gligorov, J.; André, F.; Cameron, D.; Schneeweiss, A.; Barrios, C.; Xu, B.; Wardley, Andrew M; Kaen, D.; Andrade, L.; et al. (2021)
      Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone.