Title: Capecitabine monotherapy in patients aged 70 years and older with metastatic breast cancer (MBC)
Abstract: Capecitabine monotherapy is associated with a clinical benefit rate (CBR) of 60% and a median time to progression (TTP) of 4 months in patients ≥65 years (yrs) with MBC. However, 30% require a dose reduction (DR) due to toxicity. At the Royal Marsden Hospital, the starting dose and schedule for capecitabine is 2000mg/m2 on days 1-14, every 3 weeks. Older patients (pts), with a poor performance status (PS), comorbidities and/or moderate to severe renal impairment may start with a further DR. If early CTCAE grade ≥2 toxicity occurs, a switch from 3-weekly to a week-on-week-off (WOWO) schedule is used to improve tolerance. To evaluate toxicity and efficacy of capecitabine monotherapy in pts ≥70 yrs diagnosed with MBC. Primary endpoint- toxicity. Secondary endpoints- CBR, TTP & Overall Survival (OS). From October 2013-October 2015, 77pts ≥70yrs retrospectively identified from the RMH Pharmacy Data Base received capecitabine monotherapy for MBC. Capecitabine was 1st line therapy in 65 pts (84%), with 43 & 34 receiving 2000mg/m2 & <2000mg/m2 respectively (25pts-1500mg/m2, 9 pts-1000mg/m2). Pts starting at a lower dose were older (79 yrs vs 73 yrs, p < 0.001), with more moderate to severe renal impairment (16% vs 44%, p = 0.016), ECOG PS ≥2 (11% vs 26 %, p = 0.156) & de novo metastatic disease (17% vs 35%, p = 0.09). With respect to toxicity: 8 pts (19%) in the 2000mg/m2 group had grade 3-4 toxicities vs 1 pt (3%) in the <2000mg/m2 group. 9% vs 91% in the <2000mg/m2 and 2000mg/m2 group respectively required DR. 42% in 2000mg/m2 vs 32% in the <2000mg/m2 group switched to WOWO due to early toxicity. No treatment-related deaths were observed. CBR for 2000mg/m2 & <2000mg/m2 groups was 67% vs 43% respectively (p = 0.05). After a median follow-up of 28.1 months, the combined TTP was 8.2months & OS of 18.6 months. TTP were 11.7 months and 6.2 months in the 2000mg/m2 & <2000mg/m2 groups respectively (p = 0.111). In patients aged 70 years or older, capecitabine monotherapy at a starting dose of 2000mg/m2 or lower is associated with a median TTP of 8.2 months and a CBR of 43-67%. Toxicity can be managed by dose reductions and switching to a WOWO schedule, which enables continued treatment in those deriving clinical benefit.