INCA-GYN001: Erlotinib added to cisplatin and definitive radiotherapy in untreated patients with locally advanced squamous cell cervical carcinoma—Final report of a phase II trial.

Abstract

5033 Background: Concurrent cisplatin (C) based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer (LACC). New strategies that increase the complete response (CR) rates may lead to longer progression-free(PFS) and overall survival(OS). Pre-clinical data indicates that inhibition of the epidermal growth factor receptor (EGFR) potentiates the effect of RT. We previously reported a phase I trial of the tyrosine kinase EGFR inhibitor erlotinib (E) administered concurrently with standard CRT for LACC that confirmed the safety of E at 150mg/day and preliminary efficacy data on the phase II. Methods: Eligibility - stage IIB to IIIB squamous cell cervical carcinoma; no prior therapy; ECOG PS 0-2; adequate end-organ function. Patients (pts) received E 150mg/day one week before and combined with C (40mg/m2, weekly, X 5) and RT (external beam - 4500cGy in 25 fractions, followed by 4 fractions/600cGy/weekly of brachytherapy). Pre and post treatment tumor tissue was obtained for molecular analysis.Response was assessed after a 3 month-interval with MRI, CT, PET and biopsy. Results: Patient characteristics: median age 44 (27-68), stage IIB 22 (57.9%), IIIA 1 (2.6%) and IIIB 15 (39.5%). 41 pts were enrolled and 3 excluded. 38 patients were available for toxicity. Two pts did not complete planned treatment (one presented Raynaud's Syndrome and had C interrupted and one presented grade 4 hepatotoxicity). Of 36 pts who completed E+CRT, median duration of treatment was 77 (64-129) days and median follow-up was 39.4 months(m) (IC95%35.5-43.3). Overall E+CRT was well tolerated. Most common grade 3 toxicity was skin rash (13%). Of 36 evaluable for response, 34 pts, (94.4%-IC 95% 79.99- 99.03) had CR and two pts had partial response. Cumulative OS and PFS survivals were 91.7% and 80.6% at 24m, and 80% and 73.8%, respectively, at 36m of follow-up, superior to historical control. Conclusions: In this cohort of LACC patients the combination of E+CRT is efficacious and feasible, with a CR rate of 94.4%. This combination is worth exploring in a randomized clinical trial. Molecular correlative studies will be presented at the meeting.