Weekly vinorelbine (VIN) vs weekly docetaxel (DOC) for metastatic breast cancer failing anthracyclines. Planned interim analysis of a randomized trial

Abstract

744 Background: Optimal therapy is controversial for metastatic breast cancer no longer eligible for anthracyclines. VIN and DOC are known active regimens. Methods: Randomized patients (pts) received VIN 30 mg vs DOC 35 mg/m2 weekly x 6 for ≤ 4 cyles of 8 weeks duration. Upon progression, crossing of treatment arms (CTA) was offered. Primary endpoint is time to progression (TTP), others are survival (OS), response, toxicity, and quality of life (not reported here). Analysis at 120 of 240 pts accrued was planned for evaluation of trends. Results: Of 121 pts randomized from 11/98 til 07/03, 112 are currently evaluable, VIN (n=57) vs DOC (n=55). Common risk factors are well balanced. 65 CTA pts had VIN (n=31) or DOC (n=34) as 2nd therapy. Overall median follow-up is 230 days (5–1588). Before or without CTA, VIN pts had a median of 7 doses (1–28) for a TTP of 81 days (CI: 67–99), while DOC pts had a median of 11 doses (2–24) for a slightly longer TTP of 103 days (CI: 98–119), (p= 0.1178, log-rank-test). OS for initial VIN vs DOC was 253 (CI: 173–331) vs 288 days (CI: 231–424), (p= 0.1895, log-rank-test). One year survival was 31% for VIN (CI: 20–46%) vs 44% for DOC (CI: 30–60%). More VIN pts (42%) than DOC pts (18%) had disease progression as best response (p=0.00751, Fisher's exact test, double sided); other responses slightly favored initial DOC (not significant). After CTA, DOC produced more responses (35% vs 3%, p≤ 0.0014, Fisher's exact test, double sided), but again without significant benefit in terms of TTP and OS, respectively. Generally, VIN vs DOC resulted in more treatment delays (76% vs 46%), more leukopenia (61% vs 10%) or neutropenia (43% vs 7%) grade 3/4, but less mucositis/stomatitis (1% vs 8%)-(all p<0.05, Fisher's exact test, double sided). 2/5 VIN pts with severe adverse event (SAE) died of neutropenic sepsis, or pulmonary embolism, respectively. 1/10 DOC pts with SAE died of DIC and multiorgan failure. Conclusion: DOC was more efficient at response and less toxic than VIN, both before and after crossing of treatment arms, but so far with marginal or no benefit at TTP or OS. TTP benefit may become apparent once accrual is complete. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis