VP6-2021: IMpassion050: A phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk, HER2-positive early breast cancer (EBC)
Authors: J. Huober, C.H. Barrios, N. Niikura, C. Lambertini, E. Restuccia, H. Zhang, Show all authors
Published:June 17, 2021DOI:https://doi.org/10.1016/j.annonc.2021.05.800
PH +CT is standard of care for high-risk, HER2-positive EBC. PH activates antibody-dependent cellular cytotoxicity; combining A +PH +CT may restore anti-cancer immunity and further enhance activity. IMpassion050 (NCT03726879), a double-blind, randomised, placebo (PL)-controlled study, evaluated efficacy and safety of neoadj A/PL +PH +CT. We report the primary analysis.
Patients (pts) had T2_4, N1_3, M0 disease. HER2-positivity, PD-L1 and hormone receptor (HR) status were assessed centrally. Stratification factors: T stage, HR and PD-L1 status. Randomisation was 1:1 to A/PL 840 mg q2w Cycles (C) 1_4/1200 mg q3w C5_8 +dose-dense doxorubicin +cyclo-phosphamide (ddAC) q2w C1_4 followed by paclitaxel (Pac) qw C5_8 þstandard PH q3w C5_8. Post-surgery, pts continued PH +A/PL to complete 52 weeks in total. Pts with residual disease could switch to trastuzumab emtansine +A/PL. Co-primary endpoints: Pathological complete response (pCR; ypT0/is ypN0) in the ITT and PD-L1-positive populations. Safety was a secondary endpoint. On 26/01/21 the IDMC met and recommended that A/PL treatment (Tx) be stopped due to an unfavourable benefite risk profile. Data were analysed early (clinical cutoff: 05/02/21), with 3 pts yet to undergo surgery.
226 pts were assigned to A; 228 to PL. pCR in the ITT population of the A and PL arms: 62.4% (95% CI 55.7, 68.7) and 62.7% (56.1, 69.0), respectively (Δ _0.33%; _9.2, 8.6; P ¼1.0). pCR in the PD-L1-positive population (109 per arm): 64.2% (54.5, 73.2) and 72.5% (63.1, 80.6), respectively (Δ _8.26%; _20.6, 4.0; P ¼0.2). In the neoadj phase, Grade 3/4 adverse events (AEs; 51.8% v 43.6%) and serious AEs (19.5% v 13.3%) were increased with A without increased withdrawals from any study Tx. There were 4 Grade 5 AEs in the neoadj phase (alveolitis,* septic shock,* sepsis, COVID-19 [*Tx-related, per investigator]) and 1 in the adjuvant phase (COVID-19); all with A and confounded by comorbidities and concurrent events.
A +ddAC-PacPH did not result in increased pCR in the ITT or PD-L1-positive populations. Overall, the safety profile was consistent with the known profile in other combination studies with A, with no new safety signals.