A phase 2, single agent study of CI-1033 administered at two doses in ovarian cancer patients who failed platinum therapy

5054 Background: Ovarian cancer that is refractory to platinum-based therapies is a therapeutic challenge, particularly in the setting of erbB-1 and -2 receptor over- expression. CI-1033 is an irreversible, 4-anilinoquinazoline pan-erbB tyrosine kinase inhibitor with activity in a wide variety of human tumor xenografts, particularly erbB+ tumors including ovarian SK-OV-3. Methods: This study evaluated 50- and 200mg doses of CI-1033, given daily for 21 days repeated every 28 until disease progression in pts with platinum-refractory ovarian cancer. Primary eligibility criteria included disease progression following platinum therapy, measurable disease, and Karnofsky Performance Status (KPS) of 60–100. Baseline tumor erbB receptor profiles were determined by IHC staining retrospectively in 56 of the 105 pts. Endpoints included 1-yr progression-free survival (PFS) and overall survival (OS). Results: Between January and May of 2002, 105 patients were enrolled. Baseline characteristics were balanced between both groups: overall median number of prior chemotherapy regimens was 4 (1–12); median KPS was 90. Fifty-three pts received 146 cycles in the 50-mg arm; 52 pts received 138 cycles in the 200-mg arm. Dose reductions were necessary in 59% of pts in the 200-mg arm predominantly due to gastrointestinal adverse effects (AEs); no pts required dose reductions in the 50-mg arm. The most common treatment-related AEs in the 50-mg arm were Grade 1–2 diarrhea (57%), asthenia (43%), and nausea (41%); AEs in the 200-mg arm were Grade 2–3 diarrhea (85%), stomatitis (69%), and rash (58%). There were no objective responders in either arm; stable disease (≥8 weeks) was achieved in 28% and 34% of pts in the 50- and 200-mg arms, respectively. One-yr PFS rates were 0% and 9%, and 1-year OS were 37% and 38% for 50- and 200-mg dose group, respectively. No associations were apparent between baseline tumor erbB expression profiles and PFS or OS. Conclusions: CI-1033 has minimal activity in this heavily pretreated, platinum-refractory population. The 50-mg dosing regimen was better tolerated than the 200-mg arm, with gastrointestinal AEs being most common toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Employed by Pfizer Eli-Lilly Pfizer Eli Lilly; GlaxoSmithKline

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