P1-08-01: Survival in Metastatic Breast Cancer (MBC): No Evidence for Improved Survival Following Distant Recurrence after Adjuvant Chemotherapy.
Authors: Tevaarwerk AJ , Gray R , Schneider BP , Smith ML , Wagner LI , Miller KD , Sparano JA 
Published: June 2012

Abstract
Population-based studies have suggested improved survival for patients diagnosed with MBC in recent years, presumably due to the availability of new and more effective therapies (Chia et al. Cancer 2007; Dawood et al. JCO, 2008). The objective of this analysis was to determine if survival improved for patients who participated in Eastern Cooperative Oncology Group (ECOG) adjuvant trials and later developed MBC.
Methods: Adjuvant trials coordinated by the ECOG that accrued patients between 1978 and 2002 were reviewed (n=12), which included followup until 2010. Cytotoxic and biologic agents approved for MBC during this time included paclitaxel (1994), capecitabine and trastuzumab (1998), docetaxel and gemcitabine (2004), lapatinib and ixabepilone (2007), and bevacizumab (2008). Survival following distant recurrence was estimated for 4 time periods ranging from 6–10 years, and adjusted for baseline covariates in a Cox proportional hazards model. Because distant relapse free interval (DRFI) was the covariate most strongly associated with survival after recurrence, and the potential for “gap time” bias this could introduce, logrank tests for other covariates and estimates of effects were computed stratified on DRFI (0-3, &gt;3-6, &gt; 6 years). HER2 status was not routinely available and thus not included.
Results: The 12 trials included 14,752 patients (93% received adjuvant chemotherapy); 3711 (25.2%) developed distant recurrence. Median survival after distant recurrence was 20 months; the estimated 5 and 10-year survival rates were 16.3% and 6.1%, respectively. Median survival by time period is shown in the table, stratified by DRFI. Median survival did not significantly change over time by DRFI (≤3 years, p=0.15; &gt;3 yr, p=0.57). In a Cox proportional hazards model, factors associated with inferior survival after adjusting for other covariates included shorter DRFI (&lt;3 years vs. 3–6 years — hazard ratio [HR] 1.60, p&lt;0.001, and &gt; 6 vs. &lt; 3 years — HR 2.23, p &lt;0.001), ER-negative disease (HR 1.30, p&lt;0.001), PR-negative disease (HR 1.36, P&lt;0.0001), number of positive axillary nodes at diagnosis (1-3 vs. 0 nodes — HR 1.28, 4–9 vs. 0 nodes — HR 1.51, &gt; 9 vs. 0 nodes — HR 1.51, p&lt;0.0001), and black vs. white race (HR 1.29, p=0.0003), but not age at recurrence (p=0.07). When the year of recurrence was added to the Cox proportional hazards model using the intervals shown in the table below, it was not significantly associated with survival. Results were similar when 1978–2010 was assessed by 5–6 year intervals.
Conclusions: In contrast to reports from population-based studies, we do not observe any improvement in survival over time for patients who develop distant recurrence after adjuvant chemotherapy. There remains a critical unmet need for new therapies for MBC, especially for those who recur after adjuvant chemotherapy.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-01.