Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer

Abstract

This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC.

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

“…Figure 1 outlined the selection process in detail. These trials represented three studies with sorafenib, 21,31,32 three with sunitinib, 20,33,34 three with vandetanib [35][36][37] and five with pazopanib. 2,[38][39][40][41] The characteristics of each included trial were presented in Table 2.…”

A Phase I Study of Capecitabine Combined with CPT-11 in Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes

“…Recent trials evaluating new regimens for breast cancer, particularly with molecular-targeted drugs, have thus tended to target specific subtypes to overcome the limited effects of conventional drugs and to examine new approaches to effectively suppressing the function of specific molecules that are critical for tumor growth and survival. Some negative studies using new molecular-targeted medicines have already been reported because of not meeting the trial end points for the prolongation of progression-free or overall survival [20,21]. These setbacks may be attributable to the dilution of clinical benefits by prolonged survival after progression due to other drugs, ethical limitations on clinical trials allowing cross-over administration of experimental medicines and poor cost-benefit ratios with expensive new molecular-targeted medicines [22].…”

Targeted Therapies in Triple-Negative Breast Cancer

“…Sunitinib was unable to provide any benefit either as monotherapy compared to capecitabine or in combination with chemotherapy [49,[51][52][53]. There are no specific data for triplenegative patients from these trials.…”