Mixed Results With Durvalumab Maintenance in HER2-Negative Advanced Breast Cancer

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Given as maintenance therapy, the checkpoint inhibitor durvalumab significantly improved overall survival in patients with metastatic triple-negative breast cancer and yielded a numerical but not significant benefit as well for patients expressing programmed cell death ligand 1 (PD-L1), in exploratory analyses of the phase II randomized SAFIR02-IMMUNO trial presented at the 2019 San Antonio Breast Cancer Symposium.1 In the overall mixed population of patients, however, outcomes were not improved with the drug.

Florence Dalenc, MD

Florence Dalenc, MD

“This study generates the hypothesis that durvalumab as a single agent could improve outcomes in metastatic triple-negative breast cancer, but it suggests also that durvalumab as monotherapy is not effective in the whole population of patients with estrogen receptor–positive disease,” said Florence Dalenc, MD, of the Institut Claudius Regaud, IUCT-O, Toulouse, France.

Among patients with triple-negative breast cancer in this trial (n = 82), the median overall survival was 21 months with maintenance durvalumab compared with 14 months with chemotherapy (hazard ratio [HR] = 0.54; P = .0377). In patients with PD-L1–positive disease across several breast cancer subtypes (n = 44), it was 26 months with maintenance durvalumab and 12 months with chemotherapy (HR = 0.42; P = .0552). In contrast, survival was similar between the arms for the overall study population of patients with various breast cancer subtypes: 21.7 months with durvalumab and 17.9 months with chemotherapy (HR = 0.84; P = .42), she reported.

SAFIR02 Details

Dr. Dalenc reported outcomes for 199 patients in the maintenance arm of SAFIR02, which evaluated the use of durvalumab in patients lacking a targetable mutation. The larger study enrolled 1,462 patients with locally advanced or metastatic HER2-negative breast cancer (with 2 HER2-positive patients) who had received first- or second-line chemotherapy (or prior endocrine therapy if indicated). Patients could not have a targetable molecular alteration and had to achieve a complete or partial response or stable disease following 6 to 8 cycles of chemotherapy, or 4 cycles for those with toxicity-related treatment discontinuation.

“In the overall population, maintenance durvalumab did not improve progression-free survival; in fact, patients fared better on chemotherapy.”
— Florence Dalenc, MD

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For the maintenance portion of the study, in the durvalumab arm, 37.6% of patients had triple-negative breast cancer, 60.8% had hormone receptor–positive/HER2-negative disease, and 1.6% had HER2-positive disease. The corresponding rates in the control arm were 52.2%, 47.8%, and 0%. Approximately one-third of patients in both arms tested PD-L1–positive.

Patients were randomly assigned 2:1 to durvalumab at 10 mg/kg every 14 days or maintenance chemotherapy with paclitaxel, capecitabine, and fluorouracil/epirubicin/cyclophosphamide.

Benefit Dependent on Subpopulation

In the overall population, maintenance durvalumab did not improve progression-free survival; in fact, patients fared better on chemotherapy. The median progression-free survival was 2.7 months with the PD-L1 inhibitor and 4.6 months with chemotherapy (HR = 1.40; P = .047). The hazard ratio for progression-free survival actually favored maintenance chemotherapy in most predefined patient subgroups, with the exception of those with triple-negative breast cancer (HR = 0.87; 95% confidence interval [CI] = 0.54–1.42) and those who were PD-L1–positive (HR = 0.75; 95% CI = 0.38–1.49), she reported.


  • As maintenance therapy for patients with advanced/metastatic HER2-negative breast cancer, durvalumab did not improve overall survival over chemotherapy in the overall study population of 199 patients.
  • However, maintenance durvalumab did significantly improve survival in patients with triple-negative breast cancer, reducing the risk by 46% (P = .0377), and was associated with a strong trend toward improvement (58% risk reduction; P = .0552) in patients with PD-L1–positive disease.
  • In patients with hormone receptor–positive disease, chemotherapy significantly outperformed the checkpoint inhibitor.

Outcomes in patients with hormone receptor–positive disease were noteworthy for the fact that durvalumab provided much less benefit than chemotherapy (HR = 2.08; 95% CI = 1.28–3.40; P = .0025). “For hormone receptor–positive metastatic breast cancer, exploratory analyses suggest that anti–PD-L1 as a single agent is less effective than chemotherapy as maintenance therapy,” Dr. Dalenc said.

Grade 3 or 4 treatment-related adverse events occurred in 13.2% and 15.9% of the durvalumab and control arms, respectively; they were “serious” in 8.5% and 1.6%.

The researchers hope to tease out the potential benefit of durvalu­mab in triple-negative breast cancer and to use multiplexed pathology analyses of tissue samples from SAFIR02 to determine those factors impeding the response to immunotherapy in hormone receptor–positive cancers. They also hope to find combination approaches that can improve outcomes with regimens incorporating immunotherapy. 

DISCLOSURE: Dr. Dalenc has served on advisory boards or received research or travel funds from Roche, Novartis, Lilly, Pfizer, Eisai, MSD, and AstraZeneca.


1. Dalenc F, Garberis I, Filleron T, et al: Durvalumab compared to maintenance chemotherapy in patients with metastatic breast cancer: Results from phase II randomized trial SAFIR02-IMMUNO. 2019 San Antonio Breast Cancer Symposium. Abstract GS3-02. Presented December 12, 2019.

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