Abstract P6-14-01: Final results of the TANIA randomized phase III trial of bevacizumab (BEV) after progression on 1st-line BEV therapy for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC)
Authors: Vrdoljak E , Marschner N , Zielinski C , Gligorov J , Cortes J , Puglisi F , Aapro M , Fallowfield L , Fontana A , Inbar M , Kahan Z , Welt A , Lévy C , Brain E , Pivot X , Putzu C , Gonzalez-Martin A , Ebel K , Easton V , von Minckwitz G 
Published: May 2016

BACKGROUND: The open-label randomized phase III TANIA trial (NCT01250379) evaluated 2nd-line BEV-containing therapy in BEV-pretreated LR/mBC. The primary objective was met: 2nd-line PFS was statistically significantly improved in patients (pts) receiving further BEV (hazard ratio [HR] 0.75, 95% CI 0.61–0.93; p=0.0068) [von Minckwitz, Lancet Oncol 2014]. We report final efficacy, safety, and health-related quality of life (HRQoL) results.

METHODS: Eligible pts had HER2-negative LR/mBC that had progressed on/after 1st-line BEV plus chemotherapy (CT). Pts were randomized to receive 2nd-line CT (investigator's choice) either alone or combined with BEV (15 mg/kg q3w or 10 mg/kg q2w) until disease progression (PD), unacceptable toxicity, or consent withdrawal. At 2nd PD, pts in the CT arm received 3rd-line CT without BEV (no crossover); pts initially randomized to BEV–CT received 3rd-line BEV–CT. Secondary endpoints included 3rd-line PFS, 2nd- and 3rd-line PFS (from randomization to 3rd PD/death), overall survival (OS), HRQoL, and safety. HRQoL was assessed using FACT-B at baseline, every 8/9 weeks (depending on treatment schedule) during 2nd-line therapy, and at the time of 2nd PD. Prespecified HRQoL analyses included differences between treatment arms in mean change from baseline for each FACT-B subscale.

RESULTS: At the time of data cut-off for the prespecified final analysis (April 30, 2015, 24 months after the last pt was randomized), median follow-up was 32.1 vs 30.9 months in the CT vs BEV–CT arms, respectively. All pts had stopped study treatment. Of the 494 pts randomized to 2nd-line therapy, 234 began 3rd-line therapy (105 initially randomized to CT; 129 from the BEV–CT arm, of whom 17 received CT without BEV). The most commonly selected 3rd-line CT was vinorelbine (33% of CT pts vs 31% of BEV–CT pts).

EndpointNo. of events/pts (%)Median, months (95% CI)Stratified HR (95% CI)p-value CTBEV–CTCTBEV–CT  3rd-line PFS99/105 (94)124/129 (96)2.9 (2.2-3.9)3.8 (2.4-5.1)0.79 (0.59-1.06)0.10802nd- and 3rd-line PFS177/247 (72)206/247 (83)10.7 (9.2-12.5)12.8 (10.7-14.5)0.85 (0.68-1.05)0.1349OS156/247 (63)163/247 (66)18.7 (15.4-21.2)19.7 (17.6-21.0)0.96 (0.76-1.21)0.7253

Subgroup analyses of 3rd-line PFS and OS according to stratification factors were consistent with the overall ITT result. Before study closure, 68% and 61% of pts in the 3rd-line ITT population CT and BEV–CT arms, respectively, received further CT. 3rd-line safety results showed no new safety signals. At week 8/9, mean change from baseline for all FACT-B subscales was &lt;1.5 points in either direction in both treatment arms, representing no significant difference. Similarly, exploratory HRQoL analyses of the physical and functional wellbeing subscales using mixed-model repeated measures and responder analyses revealed no meaningful significant differences between treatment arms.

CONCLUSIONS: Although BEV given after PD on 1st-line BEV-containing therapy showed improvement in 2nd-line PFS, no OS benefit was demonstrated. No new safety signals were observed. There were no differences in HRQoL between treatment arms, suggesting that the PFS benefit with BEV is achieved with maintained HRQoL.

Citation Format: Vrdoljak E, Marschner N, Zielinski C, Gligorov J, Cortes J, Puglisi F, Aapro M, Fallowfield L, Fontana A, Inbar M, Kahan Z, Welt A, Lévy C, Brain E, Pivot X, Putzu C, Gonzalez-Martin A, Ebel K, Easton V, von Minckwitz G. Final results of the TANIA randomized phase III trial of bevacizumab (BEV) after progression on 1st-line BEV therapy for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-14-01.