AZD6244 (ARRY-142886) versus capecitabine (CAP) in patients (pts) with metastatic colorectal cancer (mCRC) who have failed prior chemotherapy

Abstract

4114 Background: There is a strong correlation between human cancers and constitutive activation of the Raf/MEK/ERK signaling pathway. AZD6244, a potent, selective, ATP uncompetitive inhibitor of MEK1/2 has shown anti-tumor activity as monotherapy in several tumor models, including human colorectal tumors. This study aimed to compare the efficacy and safety of AZD6244 with that of CAP in pts with mCRC who had failed prior irinotecan and/or oxaliplatin therapy, where no standard of care exists. Methods: In this Phase II exploratory multicenter, open, two-arm parallel-group study, pts with histologically confirmed mCRC who had failed one or two previous oxaliplatin and/or irinotecan regimens were randomized 1:1 to either AZD6244 (100 mg BID) or CAP (1,250 mg/m2 BID) until objective and/or clinical progression. Eligibility included pts with a WHO performance status of 0–2 and life expectancy of >12 weeks. The primary objective was to assess the efficacy of AZD6244 vs CAP for the treatment of mCRC by assessment of disease progression. Results: A total of 69 pts (aged 38–81 years; 75% third-line) were randomized to AZD6244 (34) or CAP (35). The two groups were comparable for baseline characteristics. There was no significant difference between AZD6244 and CAP in the number of pts with a progression event: 28 pts (82%) vs 28 pts (80%), respectively (HR 1.08; 80% CI 0.73, 1.58; p = 0.80). This primary analysis was supported by a secondary analysis of PFS (AZD6244: median 81 days; CAP: median 88 days; HR 1.08; 80% CI 0.76, 1.52; p = 0.78). Most pts (97%) in both treatment arms experienced adverse events (AEs). The most common AEs with AZD6244 were dermatitis acneiform (56%), diarrhea (44%), asthenia (29%), and edema peripheral (26%). The most common AEs with CAP were palmar plantar erythrodysesthesia syndrome (56%), diarrhea (26%), nausea (26%), and asthenia (26%). Each group experienced 11 serious AEs (6 pts in each group), but no two pts experienced the same event. Conclusions: No statistically significant difference was observed between AZD6244 and CAP in the number of pts with a disease progression event. AZD6244 was well tolerated in this patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Novartis AstraZeneca Amgen, AstraZeneca, Novartis Pfizer, sanofi-aventis