TY - JOUR
T1 - Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031)
T2 - a randomised, double-blind, phase 3 trial
AU - Mittendorf, Elizabeth A.
AU - Zhang, Hong
AU - Barrios, Carlos H.
AU - Saji, Shigehira
AU - Jung, Kyung Hae
AU - Hegg, Roberto
AU - Koehler, Andreas
AU - Sohn, Joohyuk
AU - Iwata, Hiroji
AU - Telli, Melinda L.
AU - Ferrario, Cristiano
AU - Punie, Kevin
AU - Penault-Llorca, Frédérique
AU - Patel, Shilpen
AU - Duc, Anh Nguyen
AU - Liste-Hermoso, Mario
AU - Maiya, Vidya
AU - Molinero, Luciana
AU - Chui, Stephen Y.
AU - Harbeck, Nadia
N1 - Funding Information:
All authors received support from Genentech during the conduct of the study. Editorial support provided by an independent medical writer, under the guidance of the authors, was funded by the sponsor. EAM has received research support from GlaxoSmithKline; honoraria from Physician Education Resource; compensation for serving on advisory boards for AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, Roche/Genentech, Sellas Lifesciences, and TapImmune; institutional support from AstraZeneca, EMD Serono, Galena Biopharma, and Roche/Genentech; and has served as an uncompensated steering committee member for Bristol-Myers Squibb, Lilly and Roche/Genentech. HZ has received consulting fees from Roche/Genentech. CHB has received research support and consulting fees from Novartis, Pfizer, Roche/Genentech, Merck Sharp & Dohme, and AstraZeneca; consulting fees from Boehringer Ingelheim, GlaxoSmithKline, Eisai, and Bayer; and research support from AbbVie, Amgen, Astellas Pharma, Bristol-Myers Squibb, Celgene, Covance, Lilly, Medivation, Merck Serono, PharmaMar, Centro de Pesquisa em Oncologia, Pontifical Catholic University of Rio Grande do Sul, Latin American Cooperative Oncology Group, Grupo Brasileiro Estudos Câncer Mama, and INCA-Brazil. SS has received speaking and consulting fees from Chugai, Kyowa Kirin, and Novartis and speaking fees or grants, or both, from Lilly, AstraZeneca, Pfizer, Merck Sharpe & Dohme, Eisai, Takeda, and Taiho. KHJ has received personal fees from Roche, Novartis, AstraZeneca, Takeda, and Celgene. AK has received travel expenses for advisory boards for Roche, Novartis, Celgene, and Amgen. JS has received institutional and research funding from Merck Sharp & Dohme, Roche, Novartis, AstraZeneca, Lilly, Pfizer, Bayer, GlaxoSmithKline, CONTESSA, and Daiichi Sankyo. HI has received consulting fees from Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Eisai, and Kyowa Hakko Kirin and research support from Merck Sharp & Dohme, Bayer, Boehringer Ingelheim, Nihon Kayaku, and Sanofi. MLT has received research support, personal fees, and non-financial support from AbbVie, Pfizer, Merck, Tesaro, and Roche/Genentech; research support from PharmaMar, Bayer, Vertex, AstraZeneca, Calithera Biosciences, Biothera, OncoSec Medical, and EMD Serono; personal fees from Lilly, Immunomedics, G1 Therapeutics, Daiichi Sankyo, Aduro, and Celldex; and personal fees and non-financial support from Celgene. CF has received research support, personal fees, and other support from Bayer and Novartis; research support and personal fees from Pfizer, AstraZeneca, and Merck; personal fees from Astellas and Genomic Health; research grants and other support from Roche; and research grants from Amgen, Cascadian Therapeutics, Lilly, Janssen Oncology, and Zymeworks. KP has received institutional support for speaking or consulting from Pfizer, Lilly, Roche, Novartis, Mundi Pharma, AstraZeneca, Lilly, Pierre Fabre, Vifor Pharma, and Teva; travel expenses from Roche, AstraZeneca, PharmaMar, Pfizer and Novartis; and institutional research support from Sanofi and Pfizer. FP-L has received research support and personal fees from Myriad, NanoString, AstraZeneca, and Roche and personal fees from Genomic Health, Novartis, and Pfizer. SP, VM, and LM are employees and stockholders of Roche/Genentech. AND is an employee of Roche and has a patent pending relevant to this work. ML-H is an employee of Roche. SYC is an employee of and stockholder in Roche/Genentech and has a patent pending relevant to this work. NH has received personal fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche.
Funding Information:
F Hoffmann-La Roche/Genentech funded the study, provided the study drug (atezolizumab), and collaborated with academic authors on the study design, data collection, data analysis, and interpretation. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. The study drug nab-paclitaxel was provided through an agreement with Celgene. Medical writing assistance was provided by a professional medical writer funded by F Hoffmann-La Roche.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/10/10
Y1 - 2020/10/10
N2 - Background: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. Methods: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II–III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing. Findings: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7–24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1–24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50–65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34–49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6–27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57–79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38–61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4–35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3–4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group). Interpretation: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile. Funding: F Hoffmann-La Roche/Genentech.
AB - Background: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. Methods: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II–III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing. Findings: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7–24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1–24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50–65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34–49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6–27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57–79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38–61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4–35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3–4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group). Interpretation: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile. Funding: F Hoffmann-La Roche/Genentech.
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U2 - 10.1016/S0140-6736(20)31953-X
DO - 10.1016/S0140-6736(20)31953-X
M3 - Article
C2 - 32966830
AN - SCOPUS:85091795852
VL - 396
SP - 1090
EP - 1100
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10257
ER -