Capecitabine (Cap) combined with bevacizumab (Bev) with or without vinorelbine (Vin) in first-line metastatic breast cancer (MBC): First safety results from the randomized CARIN trial.

Abstract

1044 Background: In RIBBON-1, the combination of Bev with Cap as 1st-line therapy for MBC significantly improved progression-free survival (PFS) compared with Cap alone, with limited impact on tolerability. Vin and Cap are active agents with few overlapping toxicities. The CARIN trial aims to further improve efficacy by adding Vin to Cap/Bev, giving a non-taxane alopecia-sparing regimen. Methods: Patients (pts) are randomized (1:1) to receive Cap 1000 mg/m2 BID days 1–14 + Bev 15 mg/kg q3w (Arm A) or the same Cap/Bev regimen combined with iv Vin 25 mg/m2 days 1+8 (Arm B). Treatment is continued until progression or unacceptable toxicity. Key eligibility criteria include measurable or non-measurable HER2-negative MBC or locally recurrent disease, no prior chemotherapy for MBC, ECOG ≤2, and no brain metastases. Endpoints include PFS (primary), objective response rate, overall survival, and safety. As of Jan 2010, all 400 pts had been enrolled. The protocol-specified interim safety analysis includes the first 50 pts from each study arm after at least 4 cycles of study therapy. Results: Median age of all pts was 61 years. A total of 364 cycles were analyzed. 13 pts in Arm A and 11 in Arm B discontinued before completing 4 cycles due to progression or other reasons. Adverse events (AEs) led to discontinuation in 3 vs 4 pts, respectively. Average Cap dose intensity was 93.3% in Arm A and 84.6% in Arm B. Vin average dose intensity was 92.5%. Dose delays were less common in Arm A (19 cycles vs 58 in Arm B). AEs were less frequent in Arm A (467 events vs 684 in Arm B); grade 3/4 AEs were in a similar range (56 vs 81, respectively). The most common grade 3/4 AE was neutropenia (2 cases in Arm A, 30 in Arm B; 2 vs 18 pts, respectively). Typical Bev-associated grade 3/4 AEs were rare (hypertension and thromboembolic event each in 1 patient in each arm). Conclusions: The Vin/Cap/Bev regimen is tolerable. Additional AEs in Arm B were consistent with the known safety profile of Vin. Importantly, although the dose intensities were reasonably high in both arms, the slightly increased incidence of AEs in Arm B did not lead to a higher discontinuation rate. Updated results will be presented.