Prostate cancer is one of the most common types of cancer worldwide and has strong genetic associations. This is important for the development of therapeutics for the condition, as metastatic castrate-resistant prostate cancer (mCRPC) is resistant to standard androgen deprivation therapy (ADT) and has a relatively poor prognosis. We conducted a literature review on rucaparib, a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor that is currently indicated for the treatment of patients with mCRPC who harbor mutations in BRCA1/2 (homologous recombination repair [HRR] genes) and who have already tried androgen receptor-axis-targeted therapies (ARAT) and a taxane chemotherapy. We describe rucaparib's FDA approval, which was based on the results of the single-arm, open-label, Phase II TRITON2 clinical trial, which found an objective response rate (ORR) of 43.5%, a duration of response (DOR) of over six months in length and an acceptable safety profile. Rucaparib's dosage and clinical considerations for use were also discussed. We also compared rucaparib's use and safety profile with Olaparib, niraparib and talazoparib, three other PARP inhibitors tested for the treatment of mCRPC. Overall, initial results show that the safety profile of all four drugs in mCRPC was relatively similar, and further testing is currently indicated for all four. Differences in their metabolism, however, also warrant further research. The clinical validity of rucaparib will be tested by the follow-up TRITON3 clinical trial, which is comparing the effect of rucaparib compared to standard therapies for mCRPC harboring BRCA1/2 or ATM mutations. Other than TRITON3, other clinical trials are testing rucaparib's ability against other cancers (prostate or otherwise) with HRR mutations, and also the efficacy of combination therapies involving rucaparib. Finally, more research is needed to elucidate rucaparib's effect on HRR mutations other than BRCA1/2. Advancements in understanding the genetic landscape of mCRPC will also assist in understanding rucaparib's full therapeutic potential.
Cancer management and research. 2022 Nov 15*** epublish ***
Maximillian S Wu, Hanan Goldberg
Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA.