The findings were specific to patients not yet been treated with chemotherapy and whose tumors were positive for homologous recombination deficiency (HRD). However, for patients whose tumors were negative for HRD, the clinical activity was limited, said Daniel P. Petrylak, MD, Yale University, New Haven, Conn., and lead investigator for the study called CheckMate 9KD (NCT03338790) .
The patients who were included in all CheckMate 9KD cohorts had no prior treatment with targeted T-cell co-stimulation or immune checkpoint pathways. They had metastatic castrate resistant prostate cancer with documented disease progression, ECOG performance status of 0-1, and tissue available for HRD testing.
Dr. Petrylak offered an updated analysis of cohort A2 with 71 patients (median age 73 years), all of whom had received 1-2 prior new hormonal therapies in the pre-chemotherapy setting. Patients who had received prior PARP inhibitors were ineligible, as were those who refused chemotherapy treatment.
ORR/PSA RR primary endpoints
Patients received nivolumab and rucaparib, nivolumab at 480 mg (q4 weeks up to 2 years) and rucaparib at 600 mg b.i.d., until disease progression or unacceptable toxicity. Objective response rate and PSA response rate (PSA-RR) were the primary endpoint, with overall survival as a secondary endpoint, along with time to objective response, duration of objective response, time to PSA progression, safety, and radiographic progression-free survival.
Median follow-up was 17.5 months with median treatment duration of 4.6 months in the nivolumab group and 5.5 months for rucaparib. At the time of the final database lock in March 2021, 65 patients (91.5%) had discontinued treatment, most often for disease progression (n = 43; 60.6%) or study drug toxicity (n = 8; 11.3%). Four patients (5.6%) remained on treatment.
Better responses for HRD and BRCA 1/2 positive
Stratifying response outcomes showed higher rates for patients who were HRD positive and BRCA1/2 positive for confirmed objective response rate (HRD+ 25.0%, BRCA 1/2+ 33.3%, HRD-/not evaluable 5.3%, all patients 15.4%) and for PSA response (HRD+ 41.9%, BRCA 1/2+ 84.6%, HRD-/not evaluable 14.3%, all patients 27.3%). Partial response rates were 33.3% for BRCA 1/2, 25.0% for HRD positive, 5.3% for HRD- and 15.4% for all patients. Radiographic progression-free survival was longer in the HRD positive group at a median of 10.9 months (95% CI 6.7-12.0), compared with 5.6 months (3.7-9.1) in the HRD-/not evaluable group. Overall survival was similar in the HRD negative group/not evaluable group at 19.0 months (8.2-22.1) and the HRD positive group at 22.7 months (14.1-NE).