Comprehensive molecular profiling can guide treatment for rare cancers as well as it does for non-rare cancers, according to a study published in Clinical Cancer Research.

For this study, researchers evaluated whether the Drug Rediscovery Protocol (DRUP) could yield clinical benefits for patients with rare cancers, defined as cancers occurring in fewer than 6 individuals per 100,000 annually.  

DRUP was designed to match patients with refractory metastatic cancers to targeted therapies or immunotherapies that may benefit them based on their disease’s molecular profile.

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The study included 500 patients — 336 with a non-rare cancer and 164 with a rare cancer. For the entire cohort, the median age at consent was 63 (range, 53-70) years, and 54% of patients were men.

The most common rare cancers were bile duct (n=20) and central nervous system (n=23) cancers. The most common non-rare cancers were non-small cell lung (n=90) and colorectal (n=73) cancers.

Patients in the rare cancer group had received a median of 2 (range, 1-3) prior lines of systemic therapy, and patients in the non-rare group had received a median of 3 (range, 2-5).

All 500 patients were matched with and started on 1 of the 25 available drugs on DRUP.


The clinical benefit rate with matched therapy was 33% in both the rare and non-rare cancer groups. For both groups, high mutational load and alterations of ERBB2 were the most common targets that could be matched to treatment.

Patients in the rare cancer group were more likely than those in the non-rare group to have inactivating CDKN2A mutations and be matched to CDK 4/6 inhibitors (15% vs 4%; P <.001). In both patient groups, there was a “very limited benefit” with single-agent CDK 4/6 inhibitors, according to researchers.

Patients with rare cancers were more likely than those with non-rare cancers to have activating BRAF mutations and be matched to BRAF inhibitors (10% vs 1%; P <.001). Among all patients with BRAF mutations, those in the rare cancer group had a higher clinical benefit rate with BRAF inhibitor therapy (75% vs 0%).

There was no significant difference in progression-free survival or overall survival between the rare and non-rare cancer groups.

“Comprehensive molecular testing in patients with rare cancers may identify treatment opportunities and clinical benefit similar to patients with common cancers,” the researchers concluded. “Our findings highlight the importance of access to broad molecular diagnostics to ensure equal treatment opportunities for all patients with cancer.”

Disclosures: The DRUP trial is supported by Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eisai, Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Hoes LR, van Berge Henegouwen JM, van der Wijngaart H, et al. Patients with rare cancers in the Drug Rediscovery Protocol (DRUP) benefit from genomics-guided treatment. Clin Cancer Res. Published online February 10, 2022. doi:10.1158/1078-0432.CCR-21-3752