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.
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.
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.
In pts with eTNBC, A + neoadj chemo significantly improved pCR rates regardless of PD-L1 status with an acceptable safety profile.
NCT03197935.
Medical writing assistance for this abstract was provided by Christopher Lum, PhD of Health Interactions, Inc.
F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
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.