Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC).

Abstract

LBA1010 Background: Taxane-based chemotherapy (CT) improves progression-free survival (PFS) in patients (pts) with newly diagnosed HER2-negative metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor (MTKI), demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC. A randomized, open-label, multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone. Methods: Eligible pts (female; ≥18 yrs) had an ECOG PS ≤1, and newly diagnosed HER2-negative MBC or ABC. If (neo)adjuvant therapy included a taxane, relapse must have occurred ≥12 mos after CT. Pts were randomized (1:1) to treatment (tx) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2–15 q3w (Schedule 2/1; Arm A), or to D 100 mg/m2 iv 1-hr infusion q3w (Arm B) that could be given until progression. If D was discontinued in Arm A for reasons other than progressive disease (PD), single-agent SU 37.5 mg daily was permitted until PD. Median, independently assessed, PFS (primary endpoint) was compared between tx arms using stratified and unstratified log-rank tests. Overall objective response rate (ORR), overall survival (OS), pt-reported outcomes, and safety were secondary endpoints. Results: As of the data cutoff (February 1, 2010), the ITT population comprised 593 pts (SU+D, n=296; D, n=297). The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS. Baseline characteristics were well balanced. Median relative dose intensity (RDI) was 94.2% and 92.4% for SU+D, and 92.6% for D arms, respectively. Median PFS was 8.6 mos (95% CI 8.2–10.3) in the SU+D arm vs 8.3 mos (95% CI 7.7–9.6) for the D arm (HR 0.922). Median OS was 24.8 mos (95% CI 21.5–33.1) in SU+D arm vs 25.5 mos (95% CI 22.8–27.8) for D arm (HR 1.207). ORR was significantly better for SU+D (51%) vs. D (39%) (p=0.0018). Frequent all causality grade 3/4 adverse events (≥10%) were neutropenia (46%), hand–foot syndrome (17%), and fatigue (12%) in the SU+D arm and neutropenia (44%) in the D arm. Conclusions: Based on these data, SU+D is not a recommended treatment option for patients with newly diagnosed ABC. Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited. [Table: see text]

Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer

“…Two further phase III trials of sunitinib in patients with metastatic breast cancer were presented at ASCO 2010. In a first-line study, the addition of sunitinib to docetaxel significantly improved response rate (51% compared with 39%), but did not improve PFS, the primary endpoint of the study (hazard ratio 0.92; median 8.6 vs. 8.3 months) [21]. In the setting of second-line therapy or beyond, the addition of sunitinib to capecitabine did not improve PFS or response rate [22].…”

How do I Treat “Triple-Negative” Disease

“…& Tyrosine kinase inhibitors targeting angiogenesis have also been clinically investigated. One such inhibitor, sunitinib, has been evaluated alone or in combination with chemotherapy but the results have been disappointing [69][70][71]. Subset analyses of patients with triple-negative disease in these studies suggested a benefit and led to trials of sunitinib in combination with chemotherapy in the neoadjuvant setting [72].…”

BRCA-Aktivität beim triple-negativen Mammakarzinom

“…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].…”