LBA1 - Final analysis of the placebo-controlled randomised phase 3 IMpassion031 trial evaluating neoadjuvant atezolizumab (atezo) plus chemotherapy (CT) followed by open-label adjuvant atezo in patients (pts) with early-stage triple-negative breast cancer (eTNBC)

Background

IMpassion031 met its primary objective, significantly improving pathological complete response (pCR) rate with atezo added to neoadjuvant CT in pts with eTNBC (58% vs 41% with CT alone in the intent-to-treat [ITT] population; 17% difference, 1-sided p=0.0044) [Mittendorf 2020]. Benefit from atezo was seen regardless of PD-L1 status.

Methods

Pts with untreated stage II/III eTNBC and a primary tumour >2 cm were randomised 1:1 to placebo or atezo 840 mg q2w + neoadjuvant CT (nab-paclitaxel 125 mg/m² qw for 12 wk, then doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² q2w for 8 wk). After surgery, pts randomised to atezo received open-label atezo 1200 mg q3w for 11 cycles. Pts without pCR could have standard adjuvant systemic therapy (± atezo). Stratification factors were disease stage (II vs III) and PD-L1 status (IC <1% vs ≥1% by SP142). Secondary efficacy endpoints included event-free survival (EFS), disease-free survival (DFS) and overall survival (OS) in the ITT and PD-L1+ populations.

Results

After ∼39 mos’ median follow-up, EFS, DFS and OS numerically favoured atezo consistently across key clinical subgroups (Table). Among pts without pCR, 14/70 (20%) in the atezo arm vs 33/99 (33%) in the placebo arm received additional adjuvant systemic therapy, most often capecitabine (4/70 [6%] vs 26/99 [26%]). In exploratory analyses, pCR was highly prognostic for long-term outcome. Exploratory ctDNA analyses showed clearance in most pts (including all ctDNA-evaluable pts with pCR) at surgery. Positive ctDNA at/after surgery was associated with poor prognosis. There were no new safety signals or treatment-related deaths with atezo. Table: 031

Ranges in brackets are 95% CIs.

aPD-L1-expressing tumour-infiltrating immune cells on ≥1% tumour area by SP142.

bStratified.

cIn operated pts. HR = hazard ratio.

Conclusions

The significant pCR benefit with the addition of atezo to CT for eTNBC translated into numerically improved EFS, DFS and OS. Long-term safety results are consistent with previous reports.

Clinical trial identification

NCT03197935, EudraCT 2016-004734-22, Japan Pharmaceutical Information Center JapicCTI-173630.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd.), funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

C.H. Barrios: Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: GSK; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Novartis; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Pfizer; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Roche; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Eisai; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Bayer; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: MSD; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: AstraZeneca; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Zodiac; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Lilly; Financial Interests, Personal, Advisory Board, Consulting Scientific Presentations: Sanofi; 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N. Harbeck: Financial Interests, Personal, Other, Consulting: Gilead; Financial Interests, Personal, Other, Consulting: Sandoz; Financial Interests, Personal, Other, Consulting: Seagen; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Amgen; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Gilead; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Eli Lilly; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Novartis; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Pierre-Fabre; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Pfizer; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Roche; Financial Interests, Personal, Invited Speaker, Lectures, presentations, speaker’s bureaus, manuscript writing, or educational events: Seagen; Financial Interests, Personal, Leadership Role, Chair of data safety monitoring board: Roche; Financial Interests, Personal, Leadership Role: West German Study Group; Non-Financial Interests, Personal, Leadership Role: ESMO. H.A. Zhang: Financial Interests, Personal, Advisory Role: Roche/Genentech. S. Saji: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Chugai; Non-Financial Interests, Invited Speaker: Japan Breast Cancer Research Group; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Sanofi; Non-Financial Interests, Invited Speaker: Japanese Breast Cancer Society; Non-Financial Interests, Invited Speaker: Japanse Society of Medical Oncology; Non-Financial Interests, Invited Speaker: Breast International Group. K.H. Jung: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: Bixink; Financial Interests, Personal, Advisory Board: Everest Medicine; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda Pharmaceuticals; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. A. Koehler: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Daiichi; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Research Grant: German Breast Group; Financial Interests, Personal, Other, Travel/accommodation expenses: Stada. J. Sohn: Financial Interests, Personal, Stocks/Shares, Immediate Family Member: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Astra Zeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Seagen. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal and Institutional, Invited Speaker: Chugai; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker: Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Invited Speaker: Behringer; Financial Interests, Personal and Institutional, Invited Speaker: Nihon Kayaku. M.L. Telli: Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Arvinas; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Biothera; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Hummingbird Biosciences; Financial Interests, Institutional, Research Grant: Medivation; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: OncoSec; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Vertex; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Aduro Biotech; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Gilead; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: G1 Therapeutics; Financial Interests, Personal, Advisory Role: Guardant; Financial Interests, Personal, Advisory Role: Immunomedics; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Natera; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: OncoSec; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: RefleXion; Financial Interests, Personal, Advisory Role: Sanofi. 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Boileau: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: AbbVie; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Bristol-Myers-Squibb; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Vifor Pharma; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Mundi Pharma; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: McCann Health; Financial Interests, Institutional, Advisory Board: Roularta; Financial Interests, Institutional, Advisory Board: Teva; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Gilead Sciences; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Institutional, Advisory Board: Gilead; Financial Interests, Personal, Other, Consultancy: Gilead; Financial Interests, Personal, Other, Consultancy: Novartis; Financial Interests, Personal, Other, Consultancy: MSD; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Invited Speaker: Medscape; Financial Interests, Personal, Advisory Board: Astra Zeneca; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: Focus Patient; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Gilead Sciences; Financial Interests, Personal, Ownership Interest: Need Inc.; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Invited Speaker: MSD; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Leadership Role, Vice President: Belgian Society of Medical Oncology BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Leadership Role: EORTC Breast Cancer Task Force Steering Committee Member; Non-Financial Interests, Institutional, Product Samples, Drug provision for academic research: Gilead Sciences; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium; Non-Financial Interests, Advisory Role, External Scientific Advisor: European Medicine Agency. M. Dieterich: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. Z.J.F. Assaf, E. Shearer-Kang, L. Molinero, S.Y. Chui: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. T. Xu: Financial Interests, Personal, Full or part-time Employment: Roche. M. Liste Hermoso: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: Roche. E.A. Mittendorf: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Institutional, Research Grant, I have a grant from SU2C funded by Roche/Genentech that supports the conduct of a clinical trial: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Gilead provides clinical trial support to my institution for a study that I am the PI on: Gilead; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Invited Speaker: BMS; Non-Financial Interests, Invited Speaker: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role, I serve in an advisory role as a Komen Scholar: Komen for the Cure. All other authors have declared no conflicts of interest.