A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study
Mené en France sur 117 patientes atteintes d'un cancer métastatique du sein, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement d'entretien combinant exémestane et bévacizumab
Background : Maintenance strategies beyond response or tumor stabilization with first line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. Patients and Methods : In this prospective, open label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T+BEV) were randomized to continuation of T+BEV or maintenance bevacizumab plus exemestane (E+BEV). The primary endpoint was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS (PFS6m) from 50% to 65%, 186 evaluable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. Results : The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median 21-months follow up of all randomized patients (117 in total), PFS6m from randomization was 67.2% (95% confidence interval (CI) 53.6, 77.7) with T+BEV and 55.2% (95% CI 41.5, 66.9) with E+BEV (HR: 1.0, 95% CI 0.7, 1.5, p=0.998). Median PFS from BEV initiation was 12.5 and 12.3 months in the T+ BEV and E+BEV arms, respectively. In the T+BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35-months' median follow-up showed death rates of 44% and 55% in T+BEV and E+BEV arms, respectively. Conclusion : In this trial, maintenance therapy with E+BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T+BEV did not achieve longer PFS compared to continuation of T+BEV.