Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial.

The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg-1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00-1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54-1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30-0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12-1.13) for patients with PD-L1+ TNBC (n = 32) and 0.49 (95% CI: 0.18-1.34) for those with PD-L1- TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05-0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42-2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.

[Clinical practice guidelines: Standards, Options and Recommendations for first line medical treatment of patients with ovarian neoplasms (summary report)]. / Recommandations pour la pratique clinique Standards, Options et Recommandations 2003 pour le traitement médical de première ligne des patientes atteintes de tumeurs épithéliales malignes de l'ovaire, mise à jour (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To update clinical practice guidelines for first line medical treatment of patients with ovarian neoplasms in collaboration with the French Society for Gynaecologica Oncology. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts. The CPGs are defined following the definitions of the Standards, Options and Recommendations project. Once the guideline has been developed, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. After surgery, most patients with ovarian neoplasms need adjuvant medical treatment. These guidelines concern the initial medical treatment (chemotherapy, hormone treatment and immunotherapy) and potential consolidation treatment. To complete the indications, two alternative treatment strategies are taken into account: no treatment and radiotherapy. This updated version concerns the indications and the modalities of chemotherapy. The main modifications are: 1) first-line chemotherapy for ovarian neoplasm can be taxane-platinum or carboplatine alone; 2) poly-chemotherapy is no longer a standard; 3) for early stages, except for stage IA grade I non-clear-cell tumours, adjuvant chemotherapy should be preferred to no treatment; 4) chemotherapy is standard for all stage III tumours, irrespective of the surgical result; 5) for stage IA G2-3 to IIA tumours, complete surgical staging and determination of the histological grade are standards.