Maintenance erlotinib (E) following first-line treatment with docetaxel, carboplatin and erlotinib in patients with ovarian carcinoma

Abstract

5560 Background: We previously reported on the feasibility of a combination of erlotinib (E; a HER1/EGFR tyrosine-kinase inhibitor) with platinum and taxane chemotherapy (Agarwal et al, Ann Oncol 2004) and reported that almost 1/3rd patients (pts) stopped E during treatment due to toxicities which included intolerable rash, diarrhea and neutropenic sepsis. This update reports on those pts who then received E at 150mg daily as maintenance treatment. Methods: 48 pts initially received docetaxel (75 mg/m2) and carboplatin (AUC 5) following surgery q21d for 6 cycles in combination with daily oral E (50–100 mg) in dose-escalating cohorts. After 6 cycles, pts could continue with E alone (150mg/d) until progression. Results: 27 pts (56%) continued E beyond chemotherapy for a median of 8.6 months (mo) (range 2.3–32.5 mos), and 23/27 were escalated as planned to daily. Subsequently, 12/27 (44%) pts had their dose either reduced or interrupted for toxicity, which was cutaneous in 10/12 (83%) pts. However, the incidence of = grade 2 toxicity was low apart from alopecia (24%), rash (18%) and fatigue (15%). During follow-up (36 mo) 22/27 (81%) pts stopped E due to progressive disease and 3/27 (11%) stopped E due to cutaneous toxicity. Only 2/27 (7%) pts continue to receive E without evidence of progression, both at doses less than 150mg, again due to cutaneous toxicity. Pts receiving maintenance E had a median progression-free survival of 14.8 mo (95% CI 12.6–17.1 mo) and median overall survival 37.0 mo (95% ci 31.6–42.4 mo); for all pts these figures were 12.5 mo (95% CI 9.1–15.9 mo) respectively, and 37.0 mo (95% ci 27.3–46.7 mo). Conclusions: Maintenance E at 150mg daily following initial treatment with E plus docetaxel-carboplatin for ovarian carcinoma is associated with cutaneous toxicity which limits the dose and duration of treatment in a proportion of pts. The potential benefit of this approach can only be addressed in a randomized trial, and this is now underway under the auspices of the EORTC. A parallel translational study will examine the possibility that patients most likely to benefit can be predicted by molecular tumor analysis. [Table: see text]