Phase I/II lapatinib plus carboplatin and paclitaxel in stage III or IV relapsed ovarian cancer patients

Abstract

5556 Background: To establish the maximum-tolerated dose (MTD) and evaluate dose-limiting toxicities (DLTs) and response to therapy of combination therapy with carboplatin/paclitaxel and lapatinib, an oral dual tyrosine kinase inhibitor of both ErbB1 and ErbB2, in Stage III /IV relapsed ovarian cancer. Methods: This was an open-label, multicenter, phase I/II study of carboplatin/paclitaxel in combination with single agent lapatinib in Stage III/IV relapsed ovarian cancer patients. Measurable disease, adequate organ function and ECOG performance status of 0–2 were required. Patients received the metronomic maximum tolerated dose therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4 with lapatinib 1,000 mg po qd. Patients received combination therapy until disease progression. Patients were assessed for toxicity weekly and response to therapy every 8 weeks. The primary endpoints were toxicity and response to therapy. Results: 25 ovarian cancer patients are enrolled and four are too early to be evaluable. The median age is 57 (range 39–81). The median number of prior therapeutic regimens is 4 (range 1–10). GI toxicities were primarily ≤ grade 2 and were successfully treated with aggressive bowel management. 10 patients experienced grade 3 toxicities. 4- leukopenia, 2-neutropenia, 2-hyperglycemia, 2-allergic reactions to carboplatin, 1-thrombocytopenia, 1-lymphopenia, 1-hypokalemia, 1-nausea, 1-diarrhea, 1-bowel obstruction. Response to therapy to date is: CR=21%, PR=29%, SD=29%, PD=21%. Two patients who were in complete remission both stopped IV chemotherapy and were maintained only with lapatinib. One is still in remission after six months and one relapsed. Conclusions: Lapatinib, an oral targeted molecular therapy which inhibits both EGFR 1 and 2 tyrosine kinase activity, can be safely administered with a weekly regimen of carboplatin and paclitaxel in heavily pretreated, ovarian cancer patients. The high response rates seen warrant further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline