Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC).

Abstract

LBA1011 Background: Recent trials support combining an antiangiogenic agent with chemotherapy (CT) in pretreated patients (pts) with metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor demonstrated single-agent activity (11% ORR) in heavily pretreated pts with MBC. Antitumor activity with SU+C was reported in pts with advanced solid tumors. This multicenter, randomized, phase III trial (SUN 1099) compared the efficacy and safety of SU + C vs. C in pts with ABC. Methods: Eligibility criteria were: age ≥18 yrs, ECOG PS ≤1, measurable HER2-positive (FISH+, CISH+ or IHC3+) or -negative ABC, no brain metastases, prior treatment (tx) with an anthracycline and taxane in the (neo)adjuvant or metastatic setting, and ≤2 prior CT regimens for advanced disease. Prior C tx was not permitted. Pts were randomized (1:1) to combination tx with C 2,000 mg/m2/d po days 1–14 every q3w + SU 37.5 mg/d po daily, or to C 2,500 mg/m2/d days 1–14 q3w. Pts with progressive disease per RECIST on the C arm were offered single-agent SU (37.5 mg/d). Endpoints included PFS (primary), ORR, OS, QoL, and safety. Stratified and unstratified log-rank tests compared PFS between arms. Results: At the data cutoff (December 15, 2009), the ITT population comprised 442 pts: 221 in each arm with baseline characteristics well balanced between arms. The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment nor secondary endpoint of longer OS (final analysis March 10, 2010). Median PFS was 5.5 mos (95% CI 4.5–6.0) in the SU+C arm vs. 5.9 mos (95% CI 5.4–7.6) in the C arm (HR 1.224). Median OS was 16.4 mos (95% CI 13.6–18.4) for the SU+C arm and 16.5 mos (95% CI 14.2–18.6) for the C arm (HR 0.995). ORR was 18.6% for the SU+C arm and 16.3% for the C arm. The most common all causality grade 3/4 AEs (≥10%) were neutropenia (32%), hand–foot syndrome (HFS; 16%), thrombocytopenia (17%), asthenia (12%), fatigue (10%) in the SU+C arm and HFS (24%) and diarrhea (10%) in the C arm. Intended drug delivery for each arm was >80%. Discontinuations due to an AE were more frequent in the SU+C arm vs. the C arm. Discontinuations by drug in the SU+C arm: SU 39%, C 42%, SU and C 33%; in the C arm: 18%. Conclusions: Data from this randomized phase III trial do not support use of SU+C for therapy of patients with ABC. [Table: see text]

Triple-Negative Breast Cancer: One Or More Entities?

“…Tyrosine kinase inhibitors targeting the VEGF receptor have also been tested in TNBC in phase II trials. Sunitinib and sorafenib as single agents showed limited activity and significant toxicity when combined with chemotherapy [87][88][89][90]. However, in at least one trial, the combination of sorafenib with capecitabine improved PFS over capecitabine alone (4.3 versus 2.5 months).…”

BRCA-Aktivität beim triple-negativen Mammakarzinom

“…In einer Phase-III-Studie wurde der zusätzliche Einsatz von Sunitinib in der Second-lineBehandlung des fortgeschrittenen Mammakarzinoms mit alleiniger Capecitabin-Therapie verglichen. Durch Sunitinib konnte keine statistisch signifikante Verbesserung des progressionsfreien Überle-bens (PFS, primärer Endpunkt) nachgewiesen werden [51]. Ähnliche Ergebnisse zeigte auch eine Phase-III-Studie mit Docetaxel und Sunitinib vs. Docetaxel in der First-line-Behandlung des fortgeschrittenen Mammakarzinoms [52].…”

Combining Emerging Agents in Advanced Breast Cancer

“…Although both trials showed that combining sunitinib with either docetaxel or capecitabine led to a higher ORR (docetaxel: 55% versus 42%; p ϭ .001; capecitabine: 19% versus 18%), neither combination resulted in a significantly longer PFS interval (sunitinib plus docetaxel: median, 8. [56,57]. Thus, these regimens are not recommended for the treatment of patients with advanced MBC.…”