Report of first-stage accrual for NCI 5886, a phase II study of erlotinib, carboplatin and paclitaxel as first-line treatment of ovarian cancer

Abstract

5076 Background: Abnormalities in the EGFR pathway are thought to play a major role in the dysregulated growth of ovarian and related epithelial cancers. The purpose of this study is to determine whether the addition of erlotinib (erl) to the standard first line regimen of paclitaxel (T) and carboplatin (CB) encourages pathologic complete response (pCR) in patients (pts) with ovarian (OC), fallopian tube (FTC) or primary peritoneal (PPC) cancers. Tolerability and toxicity data have been previously reported (ASCO 2005). Correlative studies of EGFR and related pathways are being performed, but data is insufficient currently for presentation. Methods: Pts with a histologic diagnosis of OC, FTC or PPC Stage III or IV with either optimal (≤ 1 cm) or suboptimal residual disease within 12 weeks of initial surgery were eligible for enrollment. Pts received T (175 mg/m2) and CB (AUC 6) every 21 days, along with erl (150 mg) by mouth, daily, continuously, for a planned 6 cycles, after which pts underwent surgical reassessment to determine pCR. Data were analyzed as two parallel phase II trials in the strata of Stage III optimal (Op) and Stage III suboptimal/Stage IV (S). Both trials followed Simon’s two-stage design, with planned first stage sample sizes of 28 (Op) and 19 (S). Early stopping rules applied for ≤ 11 pCR in Op pts, and ≤3 responses in S pts. Results: Since June 2003, 47 pts have been accrued, 29 Op and 18 S. In the Op stratum, 19 second looks (SL) were performed: 10 negative, revealing pCR, and 9 positive. Two patients elected not to have SL. Six Op pts discontinued treatment prior to completion, and four pts in this group continue treatment. In the S stratum, 7 pts were treated neoadjuvantly, and 1 pt is Stage IV. Surgical reassessment was performed in 5 of the 18 S pts, all of whom had dramatic responses, but not pCR. One pt’s disease did not respond enough to the regimen to warrant surgical reassessment. One pt was ineligible, 8 discontinued treatment, and 3 continue treatment. Conclusions: First stage accrual goals have been met, and demonstrate enough activity of erl, T and Cb in OC, FTC and PPC to proceed with second stage accrual. In the S cohort, criteria for proceeding with the study are being reassessed to account for early dropouts and neoadjuvant treatment. No significant financial relationships to disclose.