Abstract LB-177: First-line bevacizumab (BEV) + chemotherapy for hormone receptor-positive metastatic breast cancer (mBC): Subgroup analysis of the open-label non-inferiority TURANDOT phase III trial.
Authors: Kahán Zsuzsanna , Petruzelka Lubos , Eniu Alexandru , Anghel Rodica , Koynov Krassimir , Vrbanec Damir , Lang Istvan , Ahlers Silke , Brodowicz Thomas , Zielinski Christoph 
Published: August 2014

Abstract
Purpose: The TURANDOT interim efficacy analysis showed no difference in OS (primary endpoint) between BEV + paclitaxel (PAC) vs BEV + capecitabine (CAP) as first-line therapy for HER2-negative mBC; progression-free survival (PFS) and response rate (RR) were superior with BEV–PAC [Lang, Lancet Oncol 2013]. We report post-hoc subgroup analyses in 433 pts with estrogen and/or progesterone receptor-positive (ER/PgR+) mBC, including subsets with aggressive disease characteristics.
Methods: Pts with HER2-negative mBC who had received no prior chemotherapy for mBC were randomized to BEV-PAC (BEV 10 mg/kg d1 & 15 + PAC 90 mg/m2 d1, 8, & 15 q4w) or BEV-CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m2 bid d1-14 q3w) until progression or unacceptable toxicity. Endocrine therapy was not allowed during study therapy.
Results: Baseline characteristics in the BEV-PAC (n=221) and BEV-CAP (n=212) arms, respectively, were: median age 60 vs 59 y; visceral metastases 65% vs 74%; &gt;10 cm sum of largest diameter (SLD) of target lesions 22% vs 20%; &gt;5–10 cm SLD 22% vs 28%; prior hormonal therapy for mBC 27% vs 26%. At data cut-off (Sep 2011, median follow-up 18.4 mo), BEV therapy was ongoing in 11% vs 10% of pts. Hormone therapy was administered after stopping study therapy in 33% vs 29% of pts. The OS hazard ratio (HR) after events in 30% was 0.92 (95% CI 0.65–1.30). The 1-year OS rate was 82% with BEV-PAC vs 84% with BEV-CAP. PFS and RR both favored BEV-PAC (PFS HR: 1.31 [95% CI 1.03–1.68; p=0.03], median 12.7 vs 8.4 mo; RR 42% vs 30% –12% difference, 95% CI –21 to –3; p=0.007). Grade (G) ≥3 treatment-emergent adverse events (AEs) occurred in 61% (8% G4, 3% G5) vs 50% (7% G4, 3% G5) of pts, respectively. AEs were consistent with previous data.
CharacteristicSubgroupOS HRa (95% CI)ECOG performance status0 (n = 285)0.93 (0.58-1.51)1/2 (n = 145)b0.97 (0.60-1.59)Disease-free interval, moNonec (n = 104)b0.87 (0.41-1.85)≤12 (n = 14)b0.88 (0.23-3.30)&gt;12 (n = 315)0.96 (0.64-1.45)SLD in target lesions, cm≤5 (n = 140)0.93 (0.52-1.69)&gt;5 (n = 197)b0.94 (0.58-1.51)Visceral metastasesYes (n = 301)b0.92 (0.62-1.36)No (n = 132)0.92 (0.44-1.90)Lymph node metastasesYes (n = 232)b1.05 (0.67-1.64)No (n = 201)0.81 (0.47-1.40)aBEV-CAP vs BEV-PACbAggressive disease characteristicscPts who either received no therapy or did not respond to therapy for primary breast cancer
Conclusion: Within the caveats of post-hoc subgroup analyses, no subset with aggressive disease characteristics was found to have a relevant OS advantage for either regimen, consistent with findings in all ER/PgR+ pts.
Citation Format: Zsuzsanna Kahán, Lubos Petruzelka, Alexandru Eniu, Rodica Anghel, Krassimir Koynov, Damir Vrbanec, Istvan Lang, Silke Ahlers, Thomas Brodowicz, Christoph Zielinski. First-line bevacizumab (BEV) + chemotherapy for hormone receptor-positive metastatic breast cancer (mBC): Subgroup analysis of the open-label non-inferiority TURANDOT phase III trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-177. doi:10.1158/1538-7445.AM2013-LB-177