First-Line Bevacizumab (Bev) Combination Therapy in Triple-Negative (TN) Locally Recurrent/Metastatic Breast Cancer (LR/MBC): Subpopulation Analysis of Study MO19391 in >2000 Patients (Pts).

Abstract

Abstract Background: The combination of Bev with taxane-based therapy, anthracycline-based combination therapy, or capecitabine significantly improves progression-free survival versus chemotherapy alone in LR/MBC, as shown in three randomized, phase III trials (E2100, AVADO, RIBBON-1). Pts with TN LR/MBC appeared to derive similar benefit from Bev compared with non-TN pts in subanalyses of the E2100 and AVADO trials. We conducted a subpopulation analysis of TN pts treated with Bev combination therapy in the MO19391 observational study, which included a broader pt population reflecting general oncology practice.Methods: Pts with HER2-negative (or trastuzumab-pretreated HER2-positive) LR/MBC received first-line Bev 10 mg/kg q2w or 15 mg/kg q3w in combination with taxane-based therapy or other non-anthracycline-containing regimen, according to physician preference. Bev was continued until disease progression. The primary endpoint of MO19391 was safety. Secondary endpoints included time to progression (TTP) and overall survival.Results: 484 of the 2041 pts in MO19391 had TN LR/MBC and 1346 had non-TN disease. The remaining 211 had missing or unknown ER, PgR, or HER2 status and were excluded from this analysis. The proportion of pts with disease-free interval (DFI) ≤24 months was considerably higher in the TN population than in non-TN pts. As expected, the safety profile of Bev combination therapy showed no differences between the two subpopulations. The only pre-defined Bev adverse events of special interest reported at grade ≥3 in >1% of TN pts were hypertension (4.5%) and pulmonary embolism (1.4%). Baseline characteristics, treatment exposure, and efficacy are summarized below. Overall survival data are immature. TN (n=484)Non-TN (n=1346)Median age, years (range)52 (24–85)54 (21–93)DFI ≤24 months, %5525>3 metastatic lesions, %6470Mean duration of Bev, months (range)5.6 (0.0–21.0)7.6 (0.0–25.6)TTP* Events, n (%)297 (61)656 (50)Median, months (95% CI)7.1 (6.4–7.6)10.6 (10.0–11.1)Response rate, %*48.354.5Complete response9.66.9Partial response38.847.6*n=483 in the TN group; n=1322 in the non-TN groupConclusions: In this ongoing study, Bev combination therapy demonstrated a 48% response rate and median TTP of 7.1 months in pts with TN LR/MBC. Findings from this observational study are consistent with retrospective analyses of randomized phase III trials. Prospective trials evaluating Bev combination regimens in TN breast cancer (adjuvant and metastatic settings) are ongoing. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6093.