Trials for Rare Cancers Are More Successful than those for Common Cancers

Rare cancers are often difficult to study in clinical practice despite their potential to yield early efficacy signals and facilitate drug development for broader indications. We compare success rates between trials studying rare versus common cancers and identify contextual factors that may influence trial outcomes over time.

We analyzed 32,145 completed trials from Trialtrove (https://citeline.informa.com/trials/results), comparing outcomes and common failure reasons between trials enrolling patients with only rare cancers, at least one rare cancer, or only common cancers. We stratified our results by treatment type, trial phase, and sponsor type. We defined rare cancers as those with incidence rates of 15 cases/100,000 person-years; our analyses were repeated using lower thresholds.

Trials enrolling only rare cancers had a 42.2% success rate, significantly higher common cancer trials (38.2%; P=6.6×10^-12). Trials including at least one rare cancer showed a similarly elevated success rate (42.5%; P=8.1×10^-15). In trials started in earlier years, "at least one rare" was more successful than "exclusively rare". However, among trials starting 2019-, the "at least one rare" and common groups have similar success rates, and "exclusively rare" trials have a higher success rate. Contrary to published assumption, poor enrollment was not a common cause of failure in rare cancer trials. Business-related failures increased substantially over the past decade, largely driven by industry-sponsored trials.

When a new therapy is applicable to both rare and common cancers, initiating trials in rare cancers may enhance rare cancer research and offer a higher probability of success.