3MO - IMpassion031: Results from a phase III study of neoadjuvant (neoadj) atezolizumab + chemo in early triple-negative breast cancer (TNBC)

Background

Preferred neoadj regimens for patients (pts) with early-stage (e)TNBC include taxane + anthracycline–based therapy. IMpassion031 is a global, Ph 3, multicentre, double-blind, randomised, placebo-controlled study in pts with high-risk primary invasive eTNBC evaluating the efficacy and safety of neoadj atezolizumab (A) or placebo (P) with nab-paclitaxel (nP) followed by A or P with dose-dense doxorubicin + cyclophosphamide. Here, we report the primary analysis of IMpassion031.

Methods

Eligible pts were ≥ 18 years old with previously untreated, centrally confirmed, invasive stage II-III eTNBC and tumour size > 2 cm. Pts (n = 333) were randomized 1:1 to receive A 840 mg or P q2w + nP 125 mg/m² qw for 6 doses of A/P followed by A 840 mg or P q2w + doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² q2w for 4 doses of A/P followed by surgery. After surgery, pathologic complete response (pCR; ypT0/isN0) was assessed in all pts and investigators were unblinded to study treatment. Stratification was by diagnosis stage (II vs III) and PD-L1 expression on tumour-infiltrating immune cells (IC; ≥ 1% vs < 1%). Co-primary endpoints were locally assessed pCR in ITT or PD-L1+ (PD-L1 IC ≥ 1%) pts. Event-free survival (EFS) was a secondary endpoint. Safety was assessed.

Results

333 pts were assigned to A-chemo (n = 165) or P-chemo (n = 168). Median follow-up was 20.6 mos in the A-chemo arm and 19.8 mos in the P-chemo arm (data cutoff 3 Apr 2020). pCR was seen in 57.6% (95% CI: 49.7, 65.2) of pts in the A-chemo arm and 41.1% (33.6, 48.9) in the P-chemo arm (Δ16.5%; 5.9, 27.1; 1-sided P = 0.0044 [significance boundary, 0.0184], P = 0.0085 for the intersection hypothesis of ITT and PD-L1+ populations). In PD-L1+ pts (n=152), pCR was seen in 68.8% (57.3, 78.9) vs 49.3% (37.6, 61.1) of pts (Δ19.5%; 4.2, 34.8; 1-sided P = 0.021; not significant). Median EFS was not reached in either arm (HR, 0.76; 95% CI: 0.40, 1.44). In the neoadj phase, Grade 3/4 adverse events (AEs) were balanced, treatment-related serious AEs occurred in 22.6% (A-chemo) and 15.6% (P-chemo), and 1 pt per arm had an unrelated Grade 5 AE.

Conclusions

In pts with eTNBC, A + neoadj chemo significantly improved pCR rates regardless of PD-L1 status with an acceptable safety profile.

Clinical trial identification

NCT03197935.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Christopher Lum, PhD of Health Interactions, Inc.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

S. Saji: Advisory/Consultancy, Speaker Bureau/Expert testimony: Kyowa Kirin; Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai; Speaker Bureau/Expert testimony: AstraZeneca; Pfizer; Novartis; Eisai; Takeda; Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Taiho. E. Mittendorf: Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: F. Hoffmann-La Roche/Genentech; Research grant/Funding (institution): GlaxoSmithKline; EMD Serono; Galena Biopharma; Honoraria (self): Physician Education Resource; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Exact Sciences; Merck; Peregrine Pharmaceuticals; Sellas Lifesciences; TapImmune; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Lilly. N. Harbeck: Research grant/Funding (self): AstraZeneca; BMS; Merck Sharpe & Dohme; Research grant/Funding (self), Non-remunerated activity/ies: Roche. H. Zhang: Advisory/Consultancy, Non-remunerated activity/ies: F. Hoffman-La Roche. C.H. Barrios: Advisory/Consultancy, Research grant/Funding (self): Pfizer, Merck, AstraZeneca, Novartis, BI, Roche/Genentech, GSK; Advisory/Consultancy: Eisai; Research grant/Funding (self): Amgen; Research grant/Funding (self): Abraxis; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (self): AB Science; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): Sanofi; Research grant/Funding (self): Taiho; Research grant/Funding (self): Mylan; Research grant/Funding (self): Merrimack; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Astellas; Research grant/Funding (self): Biomarin; Research grant/Funding (self): Asana Biosciences; Research grant/Funding (self): Medivation; Research grant/Funding (self): Exelixis; Research grant/Funding (self): ImClone Systems; Advisory/Consultancy, Non-remunerated activity/ies: Roche. R. Hegg: Non-remunerated activity/ies: F. Hoffman La Roche. A. Koehler: Travel/Accommodation/Expenses: Roche, Novartis, Celgene, Amgen. J. Sohn: Research grant/Funding (institution): Merck Sharpe & Dohme, Roche, Novartis, AstraZeneca, Lilly, Pfizer, Bayer, GSK, Contessa, and Daiichi Sankyo. H. Iwata: Advisory/Consultancy, Research grant/Funding (self), Non-remunerated activity/ies: F. Hoffman-La Roche; Honoraria (self), Advisory/Consultancy: Novartis, AstraZeneca, Pfizer, Eli Lilly, Daiichi Sankyo; Non-remunerated activity/ies: Chugai. M.L. Telli: Research grant/Funding (self), Non-remunerated activity/ies, Personal Fees: AbbVie, Pfizer, Merck, Tesaro and Roche/Genentech; Research grant/Funding (self): PharmaMar, Bayer, Vertex, AstraZeneca, Calithera Biosciences, Biothera, OncoSec Medical and EMD Serono; Advisory/Consultancy, Personal Fees: Lilly, Immunomedics, G1 Therapeutics, Daiichi Sankyo, Aduro, Celldex; Non-remunerated activity/ies, Personal Fees: Celgene. C. Ferrario: Research grant/Funding (self), Non-remunerated activity/ies, Personal Fees: Bayer, Novartis; Research grant/Funding (self), and Personal Fees: Astellas, Genomic Health, RochePfizer, AstraZeneca, and Merck; Research grant/Funding (self), Non-remunerated activity/ies, Personal Fees: Roche; Research grant/Funding (self): Amgen, Cascadian Therapeutics, Lilly, Janssen Oncology and Zymeworks. K. Punie: Honoraria (institution): Pfizer, Lilly, Roche, Novartis, Mundi Pharma, AstraZeneca, Lilly, Pierre Fabre, Vifor Pharma, Teva; Travel/Accommodation/Expenses: Roche, AstraZeneca, PharmaMar, Pfizer and Novartis; Research grant/Funding (institution): Sanofi, Pfizer. F. Penault Llorca: Research grant/Funding (self), and Personal Fees: Myriad, NanoString, AstraZeneca, Roche; Travel/Accommodation/Expenses, Personal Fees: Genomic Health, Novartis and Pfizer; Non-remunerated activity/ies: Roche. S. Patel; A. Nguyen Duc: Full/Part-time employment: F. Hoffman La Roche. M. Liste Hermoso: Full/Part-time employment: F. Hoffmann-La Roche, Ltd. V. Maiya; L. Molinero; S. Chui: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffman La Roche. K.H. Jung: Advisory/Consultancy: AstraZeneca; Roche; Novartis; Takeda; Celgene.