Beyond The Second Line Chemotherapy In Metastatic Breast Cancer: When Stop The Treatment Between Science And Conscience

Background: Women with metastatic breast cancer (MBC) are increasingly offered third line chemotherapy, but the usefulness of treatment beyond the second line remains a therapeutic challenge. The aim of this study was to determine which benefit could be brought by successive lines of chemotherapy (CT) in patients with MBC and to identify factors affecting outcome and survival. Patients and methods: This retrospective analysis included 980 women treated with CT for MBC at our Institution over a seven year period (September 1998-September 2006). With overall survival (OS) data updated at December 1, 2008, the median follow-up was 125 months (range 48-192), OS and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: Median OS evaluated from day 1 of each CT line decreased with the line number from 34.8 months (980 patients, first line, range 4-208) to 22.6 months (838 patients, second line), 14.6 months (684 patients, third line), 12.4 months (302 patients, fourth line), 9.4 months (88 patients, fifth line), 8.2 months (45 patients, seven or more lines). Median TTF ranged from 9.2 months to 7.8 and 6.4 months for the first, second and third line, respectively, with no significant decrease observed beyond the third line (median 5.2 months, range 4.8-6.2). In univariate analysis factors positively linked to a longer duration of TTF for each CT line were positive hormonal receptor status, absence of liver metastasis, adjuvant CT exposure, response to CT for the metastatic disease; in the multivariate analysis the duration of TTF for each CT line was the only one factor with significant impact on survival benefit for subsequent treatments (P Conclusions: Our results stress that CT beyond the first line may be beneficial in a significant subset of women treated for MBC. For patients responding to a given CT regimen and asking for further treatment after disease relapse, it appears useful to deliver subsequent active lines to get prolonged TTF and OS benefit. Patients who do not respond to the first two lines of CT should be considered for clinical trials or supportive care. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-03.