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Mixed Results With Rucaparib in ATLAS Trial in Metastatic Urothelial Cancer

By: Celeste L. Dixon
Posted: Monday, June 21, 2021

Results analyzing the efficacy of the PARP inhibitor rucaparib in patients with previously treated, locally advanced or metastatic urothelial carcinoma showed that no confirmed responses occurred among 95 evaluable patients, according to the phase II open-label ATLAS trial published in BMC Cancer. However, noted S. Chowdhury, MD, of Guy’s and St. Thomas’ NHS Foundation Trust and Sarah Cannon Research Institute in London, and colleagues, reductions in the sum of target lesions were observed in some patients.

The ATLAS trial enrolled 97 patients, all unselected for homologous recombination deficiency (HRD); ultimately, 20.6% were found to be HRD-positive, 30.9% were HRD-negative, and 48.5% were HRD-indeterminate. The trial results showed no apparent relationship between HRD status and efficacy, and one of the primary endpoints was a response in the HRD-positive population.

In the ATLAS trial, the investigators reported a disease control rate was 11.6% (disease control was defined as confirmed complete or partial response or stable disease lasting 16 or more weeks). In addition, rucaparib generated no unexpected safety concerns.

Since ATLAS began, however, more studies “have evaluated immune checkpoint inhibitor therapy in combination with PARP inhibitors, with the aim of improving efficacy versus immune checkpoint inhibitor [monotherapy] or PARP inhibitor monotherapy,” wrote Dr. Chowdhury and co-investigators. The PARP inhibitor olaparib plus the immune checkpoint inhibitor durvalumab generated a 35.7% response rate in patients with advanced urothelial carcinoma and DNA damage repair gene alterations in the BISCAY trial, for instance.

Future trials should continue to evaluate the potential synergy of PARP inhibitors in combination with immune checkpoint inhibitors in patients with metastatic urothelial carcinoma associated with a DNA damage repair gene alteration, the researchers suggested. In ATLAS, the incidence of deleterious alterations in a DNA damage repair pathway gene associated, in other tumor types, with increased sensitivity to PARP inhibitors (eg, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D) was “infrequent,” at just 9.4%.

Disclosure: The study authors’ disclosure information can be found at bmccancer.biomedcentral.com.



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