Data from two similar randomized phase III trials (LEA GBG51 and CALGB 40503) comparing the efficacy of standard ET versus experimental ET plus bevacizumab as first-line treatment for HR-positive MBC have been published in the European Journal of Cancer
Data comparing the efficacy of standard ET versus experimental ET plus bevacizumab in first line HR-positive patients with MBC have thus far shown conflicting results. The aim of this pooled analysis was to understand the role of bevacizumab in combination with ET in MBC and to identify subpopulations of patients that might benefit from this treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety.
The pooled sample consisted of 749 patients randomized to ET (371 patients) or ET plus bevacizumab (378 patients) arm. Baseline characteristics were well balanced between the two arms; 40% of patients had de novo advanced breast cancer and 59% recurrent disease; of whom, 88% had disease that recurred more than 2 years after initial diagnosis. Among patients with recurrent disease who received previous ET, 84% in the ET and 82% in the ET plus bevacizumab arm were endocrine-sensitive whereas 11.5% in the ET and 20.6% in the ET plus bevacizumab arm were endocrine-resistant. Median PFS was 14.3 months for ET vs 19 months for ET plus bevacizumab (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p<0.01). ORR and CBR with ET and ET plus bevacizumab were 40% vs 61% (p<0.01) and 64% vs 77% (p<0.01), respectively. There was no difference in OS (HR 0.96; 95%CI 0.77-1.18; p=0.68). PFS was superior for ET plus bevacizumab for endocrine-sensitive patients (HR 0.68; 95%CI 0.53-0.89; p=0.004). There was an increased incidence of related adverse events in the ET plus bevacizumab arm in comparison to the ET arm (44.2% vs 12.9%, p<0.001).
These results demonstrated that the addition of bevacizumab to first-line ET of MBC significantly improved PFS and ORR/CBR without any significant impact on OS and at the cost of significant toxicity.
Martín M, Loibl S, Hyslop T, De la Haba-Rodríguez J, Aktas B, Cirrincione CT, Mehta K, Barry WT, Morales S, Carey LA, Garcia-Saenz JA, Partridge A, Martinez-Jañez N, Hahn O, Winer E, Guerrero-Zotano A, Hudis C, Casas M, Rodriguez-Martin C, Furlanetto J, Carrasco E, Dickler MN; GEICAM Spanish Breast Cancer Group; GBG (German Breast Group); Alliance for Clinical Trials in Oncology (Alliance). Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials. Eur J Cancer. 2019;117:91-98.