A phase II study of paclitaxel and bevacizumab ± gemcitabine as first-line treatment for metastatic breast cancer (MBC): Interim safety results
Authors: A. M. Brufsky, K. L. Hoelzer, M. R. Keaton, J. T. Beck, E. Krill-Jackson, Y. Wang, S. Hu, L. G. Vaughn, O. O. Shonukan
Journal: Journal of Clinical Oncology (2008)

1095 Background: Paclitaxel (P) + bevacizumab (B) is a regimen that has shown significant improvement in PFS in pts with MBC. We are currently conducting a randomized Phase II trial to examine the efficacy and safety of adding gemcitabine (G) to the PB doublet. Here, we report results of a planned interim safety analysis of the first 50 treated pts. Methods: This US, multicenter, randomized, superiority trial plans to enroll 180 women. Eligible pts have locally advanced or metastatic breast cancer, PS 0 or 1, and have not received prior cytotoxic therapy for metastatic disease. Prior adjuvant or neoadjuvant treatment with a taxane or endocrine therapy is allowed. Pts assigned to Arm A receive P 90 mg/m2 on Days 1, 8, and 15, followed by B 10 mg/kg on Days 1 and 15 of a 28-day cycle. Pts assigned to Arm B receive the same regimen plus G 1,500 mg/m2 on Days 1 and 15. The primary outcome measure is response rate, and safety is one of the secondary endpoints. Results: Between May 2006 and January 2007, fifty qualified women were treated (Caucasian 70%, Hispanic 14%, African 8%, East Asian 8%). Arm A pts (N=24): median age, 60 (range 37–75); ER status ±/unknown, 14/8/2; PR status ±/unknown, 11/11/2; PS 0/1, 14/10. Arm B patients (N=26): median age, 54 (range 40–80); ER status ±/unknown, 17/7/2; PR status ±/unknown, 14/10/2; PS 0/1, 16/10. There were no discontinuations due to AEs in Arm A. Two Arm B pts discontinued from study for treatment-related AEs (rash, proteinuria). One on-study death has occurred in an Arm B pt, unrelated to treatment. Drug exposure and AE data are summarized in the following table. Conclusions: Therapy with PB ± G does not appear to be associated with significant bleeding or thrombotic events. As expected, the addition of G to the PB doublet appears to increase the incidence of neutropenia in pts with MBC. Enrollment is complete and we expect disclosure of full efficacy and safety results in the near future. Arm A N=24 Arm B N=26 P B P B G Median cycles received # (range) 5 (2–8) 5 (2–8) 4.5 (1–10) 4.5 (1–10) 4.5 (1–10) Median dose intensity (%) 87.4 91.1 80.7 85.8 80.7 Arm A N=24 Arm B N=26 Hematologic events Grade 3 n (%) Grade 4 n (%) Grade 3 n (%) Grade 4 n (%) Neutropenia 3 (12.5) 2 (8.3) 6 (23.1) 1 (3.8) Febrile neutropenia 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) Anemia 1 (4.2) 0 (0.0) 0 (0.0) 0 (0.0) Thrombocytopenia 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) Nonhematologic events * Fatigue 3 (12.5) 0 (0.0) 4 (15.4) 0 (0.0) Anorexia 0 (0.0) 0 (0.0) 2 (7.7) 0 (0.0) Cellulitis 0 (0.0) 0 (0.0) 2 (7.7) 0 (0.0) Injection site infection 0 (0.0) 0 (0.0) 2 (7.7) 0 (0.0) Arm A N=24 Arm B N=26 Alopecia, bleeding and thrombotic events, all grades n (%) Grade 1 Grade 2 Grade 3 Grade 4 Grade 1 Grade 2 Grade 3 Grade 4 Alopecia 4 (16.7) 6 (25.0) NA NA 2 (7.7) 9 (34.6) NA NA Epistaxis 7 (29.2) 0 (0.0) 0 (0.0) 0 (0.0) 10 (38.5) 1 (3.8) 0 (0.0) 0 (0.0) Mouth hemorrhage 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) 0 (0.0) 0 (0.0) Hemoptysis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) 0 (0.0) 0 (0.0) Pulmonary hemorrhage 1 (4.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Urethral hemorrhage 0 (0.0) 1 (4.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Hematuria 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) 0 (0.0) 0 (0.0) Vaginal hemorrhage 0 (0.0) 1 (4.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Hemorrhoidal hemorrhage 1 (4.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Rectal hemorrhage 1 (4.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) 0 (0.0) Deep vein thrombosis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.8) 0 (0.0) * Events occurring in ≥5% of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly AstraZeneca Oncology, Aventis Abraxis Oncology, AstraZeneca Oncology, Aventis, Eli Lilly, Genentech™ BioOncology Eli Lilly