In:
Nature Medicine, Springer Science and Business Media LLC, Vol. 28, No. 12 ( 2022-12), p. 2573-2583
Abstract:
Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1 positive disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 ) 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 positive ( n = 27; HR = 0.65; 95% CI 0.27–1.54) and PD-L1 negative 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.
Type of Medium:
Online Resource
ISSN:
1078-8956
,
1546-170X
DOI:
10.1038/s41591-022-02126-1
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
1484517-9