Standard anthracycline-based vs. docetaxel-capecitabine in early breast cancer: Results from the chemotherapy randomization (R-C) of EORTC 10041/ BIG 3-04 MINDACT phase III trial.

Abstract

516 Background: The MINDACT trial demonstrated that 46% of breast cancer patients (pts) at high clinical (C) but low genomic (G) risk based on MammaPrint (70-gene signature), might safely forego adjuvant CT (Cardoso NEJM 2016). A second 1:1 randomization (R-C) was optional in all pts for whom CT was decided, between standard anthracycline-based regimens (AT) and experimental docetaxel 75 mg/m² IV + oral capecitabine 825 mg/m² bid x 14 days (DC), q3wks for 6 cycles after surgery. Methods: MINDACT included 6693 pts, of whom 2895 received CT. C-low/G-low pts were allocated to no CT, C-high/G-high to CT and those with discordant G/C results were randomized to use either G or C risk to decide use of CT. Primary endpoint for R-C was disease-free survival (DFS). Secondary endpoints included OS and safety. Statistical hypothesis: HR-0.76 in favour of DC. Results: A total of 1301 pts (45%), of whom 787 (61%) were C-high/G-high, 351 (27%) C-high/G-low, 137 (11%) C-low/G-high, and 26 (2%) C-low/G-low, were randomized to AT or DC. Main reason for not inclusion in R-C was CT given outside the trial. Compliance rates for R-C were 97% overall. At 5-years median follow-up, DFS was not significantly different between AT (649 pts) and DC (652 pts) [HR = 0.83 (0.60- 1.15, p = 0.263], and OS was similar in both arms (HR 0.91, 95% CI, 0.54- 1.53). For the relevant C-high/G-high group, DFS was also not different (5-years DFS 86.1 vs 88.1%; HR 0.83, 95% CI, 0.58-1.21). Of note, number of events is still small (AT: 30; DC: 27). Commonest adverse events in DC were grade 2 hand/foot syndrome (28.5% vs 3.3%), grade 2 diarrhea (13.7% vs 5.8%) and grade 1 peripheral neuropathy (27.1% vs 11.2%). Grade 2 anemia (14.2% vs 5.1%) and grade 4 neutropenia (24.6% vs 20.5%) were higher in AT. Cardiac events occurred in 9 pts overall, including 1 cardiac failure (AT), while 53 pts developed secondary cancers (AT: 32; DC: 21; leukemia: 2 in AT vs. 1 in DC). Four deaths occurred (AT:1 and DC:3) while on therapy. Conclusions: Docetaxel-capecitabine did not improve DFS or OS, compared with standard anthracycline-based CT, including for the C-high/G-high group. Safety profile of both regimens was as expected. Clinical trial information: NCT00433589.