In patients with metastatic, castration-resistant prostate cancer with a BRCA alteration, rucaparib produced significantly increased progression-free survival compared with physician’s choice of a control medication, TRITON3 investigators report.
The randomized, controlled, phase 3 trial included patients who had metastatic, castration-resistant prostate cancer with a BRCA1, BRCA2, or ATM alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI). Randomization to oral rucaparib 600 mg twice daily or a physician’s choice of docetaxel or a second-generation ARPI (abiraterone acetate or enzalutamide) showed these effects on a primary outcome of the median duration of imaging-based progression-free survival: “Of the 4,855 patients who had undergone prescreening or screening, 270 were assigned to receive rucaparib and 135 to receive a control medication (intention-to-treat population); in the two groups, 201 patients and 101 patients, respectively, had a BRCA alteration. At 62 months, the duration of imaging-based progression-free survival was significantly longer in the rucaparib group than in the control group, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval [CI], 0.36 to 0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P <0.001 for both comparisons). In an exploratory analysis in the ATM subgroup, the median duration of imaging-based progression-free survival was 8.1 months in the rucaparib group and 6.8 months in the control group (hazard ratio, 0.95; 95% CI, 0.59 to 1.52). The most frequent adverse events with rucaparib were fatigue and nausea.”
The authors provide this perspective in their discussion of these results: “Previous studies involving men with metastatic, castration-resistant prostate cancer have been criticized for their choice of comparator drugs. For example, in multiple studies — including the PROfound, IMbassador250, and KEYNOTE-641 trials — enzalutamide or abiraterone acetate was used as a comparator in patients with disease that had progressed while the patient was receiving the alternative (or an identical) drug, an approach that does not represent evidence-based standard of care. In contrast, in TRITON3, physicians could choose between docetaxel and a second-generation ARPI that was newly prescribed for the patient, a trial design that provides a more robust treatment comparison. The benefit of rucaparib over docetaxel was striking, given that numerous other studies either did not include docetaxel in the control group or did not show the superiority of the intervention to docetaxel.”