Search
Close
Search
Advanced Search
Search Menu
AI Discovery Assistant

Extract

Recently, Gupta et al. retrospectively evaluated phase I studies of molecularly targeted agents sponsored by the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP) ( 1 ). They observed a trend for increased response rate (≥61% maximum tolerated dose [MTD] vs ≤60% MTD; odds ratio [OR] = 1.56; P = .10) and statistically significantly improved overall survival (≥61% MTD vs <20% MTD; hazard ratio = 0.37; P = .008) with higher doses. They state their findings contradict results published by our group at MD Anderson Cancer Center (MDACC) that showed low doses (≤25% MTD) yielded similar outcomes to medium (>25% to <75% MTD) and high doses (≥75% MTD) ( 2 ). Gupta et al. postulate 3 reasons for diverging observations: 1) NCI-CTEP and MDACC trials were multi- vs single-institutional, respectively; 2) sample sizes were different; and 3) study periods were different.

One important distinction between the two studies is the difference in efficacy endpoints. Our study compared disease control rate, which includes patients with prolonged stable disease, and time to treatment failure (TTF), which includes patients off-study for any reason (often toxicity), across dose groups. However, when we analyze response rate as complete or partial response and dichotomize at 60% of MTD as did Gupta et al., we find increased response with increased dose (OR = 1.96; P = .12). Additionally, 1-year overall survival was approximately 80% vs. approximately 40% in the NCI-CTEP vs. MDACC studies, suggesting populations may differ considerably.

You do not currently have access to this article.
Download all slides