Phase I clinical trials in refractory colorectal cancer (CRC): Do older adult patients benefit?

Abstract

784 Background: Current clinical trial data are largely driven by younger participants, yet half the population diagnosed with CRC are 70+. Upon progression, many CRC patients (pts) with refractory cancer are referred to phase 1 clinical trials; however, tolerability and clinical benefit is unclear in the elderly. Given our robust phase 1 program, we assessed the efficacy and safety of early therapeutics in the elderly CRC pts. Methods: A historical cohort analysis included mCRC pts enrolled amongst 44 phase I trials from 3/2004 - 9/2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Results: 139 pts, median age 59 (33-81), 70+ 16.5% (n = 23); KRAS mut 39.4 %. ≥3 prior lines of therapy 73.9 %; Prior EGFR-I 75.5% (100% of KRAS wt). Location: Right 20.9 %, Left 61.9 %, Transverse 4.3 %, Unknown 12.9 %. Phase I agents: VEGF I 19.4%, EGFR/Growth Factor I 9.3%. mOS for < 70 (n = 108) vs 70+ (n = 22): 6.5 vs 4.2 months (HR 1.88, p 0.007). mPFS for < 70 (n = 116) vs 70+ (n = 23): 2.0 months vs x 1.5 months (HR 1.73, P 0.03). There was not a statistical difference between < 70 versus 70+ in regards to dose cohort, number of cycles completed, or adverse events. Survival analysis in terms of risk factors in pts 70+ are in the Table below. Conclusions: Elderly CRC pts are underrepresented (16.5%) in phase 1 clinical trials and have worse survivals than non-elderly pts. Elderly CRC pts with liver and hematologic toxicities had a trend toward worse PFS but no OS. Phase I studies should incorporate prospective assessments to identify risk factors of morbidity and mortality in elderly CRC pts. [Table: see text]