KEY TAKEAWAYS
- Phase 3 TRITON-3 study aimed at evaluating the Phase 2 data of the efficacy of the drug Rucaparib in treating patients with metastatic, castration-resistant prostate cancer.
- The patients in the study had received prior ARPI treatment but suffered disease progression, and had associated BRCA alterations.
- The median evaluated in the study was significantly higher than that with a control drug of the physician’s choice with the rPFS being 1.3-5.8 months longer across various subgroups.
- Rucaparib showed longer progression-free survival than control in metastatic, castration-resistant prostate cancer with BRCA alteration.
In the phase III TRITON-3 study, Rucaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, which demonstrated efficacy in patients suffering from metastatic, castration-resistant prostate cancer associated with a deleterious BRCA alteration in Phase II of the study was analyzed with the data and expanded upon.
The phase 3 trial was randomized and controlled. The patients were enrolled subject to metastatic, castration-resistant prostate cancer with a BRCA1, BRCA2, or ATM alteration. These patients received prior treatment with a second-generation androgen-receptor pathway inhibitor (ARPI) after which suffered disease progression. Patients were randomly assigned in 2:1 ratio groups wherein one of the group received 600 mg of Rucaparib orally twice a day and the other group received a control based on the physician’s choice (usually: Docetaxel or a second-generation ARPI [abiraterone acetate or enzalutamide]).
The Primary Outcome Measure was the Radiographic Progression-free Survival (rPFS) that
was taken as the median duration of imaging-based PFS based on the independent review. In the study, 270 patients were assigned to receive Rucaparib of which 201 had a BRCA alteration; and 135 received a control medication wherein 101 patients had a BRCA alteration. The groups were further divided into BRCA subgroup, ATM subgroup, and intention-to-treat group.
The duration of imaging-based PFS was significantly longer with this drug than with a control. The median was, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval [CI], 0.36 to 0.69) in BRCA subgroup and 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001 in the intention-to-treat group.
While the analysis of the data from the ATM subgroup, the median was 8.1 months in the Rucaparib group and 6.8 months in the control group with other stats being, hazard ratio, 0.95; 95% CI, 0.59 to 1.52.
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2214676
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02975934
Fizazi, K., Piulats, J. M., Reaume, M. N., Ostler, P., McDermott, R., Gingerich, J. R., Elias Pintus, E., Sridhar S. S., Bambury, R. M., Emmenegger, U., Lindberg, H., Morris, D., Nolè, F., John Staffurth, J., Redfern, C., Sáez, M. I., Abida, W., Daugaard, G., Heidenreich, A., Krieger, L., Brieuc Sautois, B., Loehr A., Despain D., Heyes C. A., Watkins S. P., Chowdhury, S., Ryan, C. J. & Bryce, A. H. (2023). Rucaparib or Physician’s Choice in Metastatic Prostate Cancer. New England Journal of Medicine, 0(0), null. https://doi.org/10.1056/NEJMoa2214676
