Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial

• Published in: Nature medicine Vol. 28; no. 12; pp. 2573 - 2583
• Main Authors: Røssevold, Andreas Hagen, Andresen, Nikolai Kragøe, Bjerre, Christina Annette, Gilje, Bjørnar, Jakobsen, Erik Hugger, Raj, Sunil Xavier, Falk, Ragnhild Sørum, Russnes, Hege Giercksky, Jahr, Thea, Mathiesen, Randi Ruud, Lømo, Jon, Garred, Øystein, Chauhan, Sudhir Kumar, Lereim, Ragnhild Reehorst, Dunn, Claire, Naume, Bjørn, Kyte, Jon Amund
• Format: Journal Article
• Language: English; Norwegian
• Published: United States Nature Publishing Group 01.12.2022; Nature Portfolio; Nature Publishing Group US
• Subjects: Anthracycline; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - adverse effects; B7-H1 Antigen - therapeutic use; Breast cancer; Chemotherapy; Clinical trials; Cyclophosphamide; Cyclophosphamide - adverse effects; Disease control; Double-Blind Method; Double-blind studies; Doxorubicin; Humans; Immune checkpoint inhibitors; Immunogenicity; Immunomodulation; Immunotherapy; Metastases; Metastasis; Monoclonal antibodies; PD-1 protein; PD-L1 protein; Placebos; Subgroups; Survival; Targeted cancer therapy; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-022-02126-1

Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1 disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 , 24 May 2017) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n = 40) or placebo (placebo-chemo; n = 28). Primary endpoints were descriptive assessment of progression-free survival in the per-protocol population (>3 atezolizumab and >2 PLD doses; n = 59) and safety in the full analysis set (FAS; all patients starting therapy; n = 68). Adverse events leading to drug discontinuation occurred in 18% of patients in the atezo-chemo arm (7/40) and in 7% of patients in the placebo-chemo arm (2/28). Improvement in progression-free survival was indicated in the atezo-chemo arm in the per-protocol population (median 4.3 months versus 3.5 months; hazard ratio (HR) = 0.57; 95% confidence interval (CI) 0.33-0.99; log-rank P = 0.047) and in the FAS (HR = 0.56; 95% CI 0.33-0.95; P = 0.033). A numerical advantage was observed for both the PD-L1 (n = 27; HR = 0.65; 95% CI 0.27-1.54) and PD-L1 subgroups (n = 31; HR = 0.57, 95% CI 0.27-1.21). The progression-free proportion after 15 months was 14.7% (5/34; 95% CI 6.4-30.1%) in the atezo-chemo arm versus 0% in the placebo-chemo arm. The addition of atezolizumab to PLD/cyclophosphamide was tolerable with an indication of clinical benefit, and the findings warrant further investigation of PD1/PD-L1 blockers in combination with immunomodulatory chemotherapy.