Phase III study (PRIME/20050203) of panitumumab (pmab) with FOLFOX compared with FOLFOX alone in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Pooled safety data

Abstract

4034 Background: Pmab is a fully human anti-EGFr monoclonal antibody (MAb) with activity as a single agent in refractory mCRC. PRIME study is the first global, phase III trial investigating a fully human anti-EGFr MAb combined with FOLFOX as first-line treatment (tx) for pts with mCRC. Methods: This is a randomized, multicenter, phase III study with pt eligibility criteria which include: histologically/cytologically-confirmed adenocarcinoma of the colon or rectum with metastatic disease; no prior chemotherapy or systemic therapy for mCRC; ECOG performance status (PS) 0 to 2. No EGFr staining is required for inclusion. Pts are randomized 1:1 to receive either pmab 6.0 mg/kg Q2W + FOLFOX4 Q2W (Pmab+FOLFOX4) or FOLFOX4 Q2W alone. The primary endpoint is progression-free survival. Secondary endpoints include overall survival, objective response rate, time to progression, duration of response, and safety. PRIME study endpoints will be investigated by the pts’ KRAS mutational status in both arms as a potential biomarker for pmab activity in combination with FOLFOX as first-line tx for pts with mCRC. The study has multiple, planned safety interim analyses conducted by an independent Data Monitoring Committee (DMC), with the latest safety interim analysis including 601 pts of approximately 1150 target accrual. Results: 302 pts are in the Pmab+FOLFOX4 arm and 299 pts are in the FOLFOX4 arm. Of all pts, 63 % are men, median age is 62 years (range, 27- 83), ECOG PS 0: 57 %, PS 1: 38 %, PS 2: 5 %. Of all pts, 99 % received tx with at least 1 cycle of study therapy, and 39 % have stopped study tx. Median follow-up time was 15 weeks. Adverse events of interest are shown (table). Conclusions: After the safety interim analysis of the first 601 pts conducted by the DMC, PRIME study continues per protocol. PRIME study has reached the enrollment goal and updated pooled safety data for approximately 900 pts will be presented. Adverse Events of Interest: Pooled Analysis of 601 pts Adverse Event MedDRA terms Any Grade - n (%) CTC AE v3.0 Grade 3/4 - n (%) CTC AE v3.0 Skin and subcutaneous tissue SOC * 324 (54) 67 (11) Diarrhea 261 (43) 58 (10) Nausea 233 (39) 16 (3) Neutropenia 226 (38) 147 (25) Fatigue 162 (27) 25 (4) Hypomagnesaemia 68 (11) 11 (2) Dehydration 28 (5) 14 (2) Infection 4 (1) 0 (0) * SOC = system organ class. There was 1 investigator-reported adverse event of infusion reaction (grade 1). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen, AstraZeneca, Eli Lilly, Merck Serono, Roche, sanofi-aventis Amgen Abraxis, Amgen, AstraZeneca, Eli Lilly, Merck, Ortho Biotech, Roche, sanofi-aventis Amgen, Roche, sanofi-aventis Amgen