(UroToday.com) The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Nobuaki Matsubara discussing subgroup analyses of the all-comers cohort from TALAPRO-2 by HRR status. Co-inhibition of the AR and PARP may result in enhanced benefit in the treatment of prostate cancer, regardless of alterations in DNA damage response genes involved either directly or indirectly in Homologous Recombination Repair (HRR).
The randomized, phase 3, placebo-controlled TALAPRO-2 study demonstrated statistically significant improvements in radiographic progression-free survival (rPFS) for first-line talazoparib + enzalutamide vs placebo + enzalutamide in patients with mCRPC in all-comers and in HRR subgroups (HRR-deficient and HRR-non-deficient or unknown).1 At the 2023 ESMO annual congress, Dr. Matsubara and colleagues reported baseline characteristics and secondary efficacy and safety endpoints for all-comers by HRR status.
Patients randomized 1:1 to talazoparib 0.5 mg or placebo, + enzalutamide 160 mg/day, were stratified by prior abiraterone or docetaxel for castration-sensitive prostate cancer (yes vs no) and by HRR status (HRR-deficient vs HRR negative/unknown). The primary endpoint was rPFS by BICR per RECIST 1.1/PCWG3. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to PSA progression, time to initiation of cytotoxic chemotherapy, time to progression on first subsequent antineoplastic therapy or death (PFS2), and safety. The data cutoff for this analysis was March 28, 2023.
Among 805 enrolled patients, all had prospective tumor tissue HRR test results. Overall, baseline characteristics were relatively well-balanced between treatment groups and by HRR status; however, in the younger group (age <65 years), there were more HRR-deficient (29.6%) than HRR-negative/unknown (19.3%) patients, and HRR-deficient patients had evidence of more aggressive disease:
Analysis by baseline disease characteristics showed that patients with HRR-deficient disease tended to have shorter time from initial diagnosis of prostate cancer to randomization date, and higher Gleason score (>= 8), median baseline PSA, and lymph node involvement:
Overall survival data remain immature (39% of patients in the talazoparib group and 43% in the placebo group had died at data cutoff), with an HR of 0.57 (95% CI 0.36 – 0.91) in favor of talazoparib + enzalutamide in the HRR-deficient group and HR 0.93 (95% CI 0.73-1.19) in the HRR negative/unknown group. Talazoparib + enzalutamide improved objective response rate in all groups:
Additionally, talazoparib + enzalutamide prolonged time to PSA progression, time to initiation of cytotoxic chemotherapy, and PFS2 versus placebo + enzalutamide, with benefits seen in both HRR-deficient and HRR negative/unknown subgroups. Overall, patients treated with talazoparib + enzalutamide who received abiraterone for CSPC had a 43% reduction in the risk of rPFS, however only 6% of patients in either treatment group had received prior abiraterone. Similarly, patients with prior docetaxel had a 49% reduction in progression risk in the talazoparib + enzalutamide group. A similar safety profile was observed between the all-comers cohort (HRR-deficient and HRR negative/unknown) and the overall HRR-deficient population. The most common all-cause treatment emergent adverse events were anemia (66%/65%), neutropenia (36%/32%), and fatigue (34%/33%).
Dr. Matsubara concluded his presentation discussing subgroup analyses of the all-comers cohort from TALAPRO-2 by HRR status with the following concluding statements:
- Talazoparib + enzalutamide demonstrated improvements in secondary efficacy endpoints over placebo + enzalutamide as first-line treatment in patients with mCRPC in both HRR-deficient and HRR negative/unknown subgroups
- Although survival data are immature, interim data favored the combination in HRR-deficient subgroup
Presented by: Nobuaki Matsubara, National Cancer Center Hospital East-Kashiwa, Kashiwa, Japan
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
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