Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment

Louisa R. Hoes, Jade M. van Berge Henegouwen, Hanneke van der Wijngaart, Laurien J. Zeverijn, Daphne L. van der Velden, Joris van de Haar, Paul Roepman, Wendy J. de Leng, Anne M. L. Jansen, Erik van Werkhoven, Vincent van der Noort, Alwin D. R. Huitema, Eelke H. Gort, Jan Willem B. de Groot, Emile D. Kerver, Derk Jan de Groot, Frans Erdkamp, Laurens V. Beerepoot, Mathijs P. Hendriks, Egbert F. SmitWinette T. A. van der Graaf, Carla M. L. van Herpen, Mariette Labots, Ann Hoeben, Hans Morreau, Martijn P. Lolkema, Edwin Cuppen, Hans Gelderblom, Henk M. W. Verheul, Emile E. Voest

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25 Citations (Scopus)


Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients with rare cancer benefit from approved anticancer drugs outside their label similar to common cancers. Experimental Design: In the Drug Rediscovery Protocol (DRUP), patients with therapy-refractory metastatic cancers harboring an actionable molecular profile are matched to FDA/European Medicines Agency–approved targeted therapy or immunotherapy. Patients are enrolled in parallel cohorts based on the histologic tumor type, molecular profile and study drug. Primary endpoint is clinical benefit (complete response, partial response, stable disease ≥ 16 weeks). Results: Of 1,145 submitted cases, 500 patients, including 164 patients with rare cancers, started one of the 25 available drugs and were evaluable for treatment outcome. The overall clinical benefit rate was 33% in both the rare cancer and nonrare cancer subgroup. Inactivating alterations of CDKN2A and activating BRAF aberrations were overrepresented in patients with rare cancer compared with nonrare cancers, resulting in more matches to CDK4/6 inhibitors (14% vs. 4%; P ≤ 0.001) or BRAF inhibitors (9% vs. 1%; P ≤ 0.001). Patients with rare cancer treated with small-molecule inhibitors targeting BRAF experienced higher rates of clinical benefit (75%) than the nonrare cancer subgroup. Conclusions: Comprehensive molecular testing in patients with rare cancers may identify treatment opportunities and clinical benefit similar to patients with common cancers. Our findings highlight the importance of access to broad molecular diagnostics to ensure equal treatment opportunities for all patients with cancer.
Original languageEnglish
Pages (from-to)1402-1411
Number of pages10
JournalClinical Cancer Research
Issue number7
Publication statusPublished - 1 Apr 2022

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