KEY TAKEAWAYS
- Phase 3 trial TALAPRO-2 aimed to explore the benefits of combining TALA with ENZA as a first-line treatment of mCRPC compared to ENZA and Placebo combination.
- All patients received the same amount of ENZA, with one group receiving 0.5mg of TALA and the other got a placebo.
- Tumor tissue and/or blood samples were analyzed in the tri
- The TALA+ENZA combination demonstrated a lot of potential with an increased median and OS, proving to be an effective 1L treatment.
The phase 3 trial TALAPRO-2 is the first to combine the androgen receptor inhibitor ENZA with the poly(ADP-ribose) polymerase inhibitor (PRAPi) TALA. Patients were given either TALA + ENZA or PBO + ENZA as a 1L treatment for mCRPC.
Patients were stratified for castration-sensitive PC and HRR gene alteration status based on prior abiraterone or docetaxel treatment. Patients were randomized 1:1 to TALA 0.5 mg or PBO (all patients got ENZA 160 mg daily). Important eligibility requirements include mildly or asymptomatically progressing mCRPC at study entry, an ECOG PS 1, ongoing androgen deprivation treatment, and a lack of previous CRPC life-prolonging therapy. Imaging-based progression-free survival (ibPFS) by BICR, according to RECIST 1.1 and PCWG3 is the primary outcome.
TALA + ENZA and 403 PBO + ENZA were randomly assigned to 402 patients each. Tumor tissue was used to guide enrollment for 804 (99.9%) of these 805 patients, tumor tissue and blood for 114 (14.2%), and blood only for 1 (0.1%). In the TALA + ENZA vs. PBO + ENZA group, the median ibPFS by BICR was significantly improved (not reached vs. 21.9 months, respectively; HR, 0.63; 95% CI, 0.51-0.78; P 0.001). In the TALA + ENZA vs PBO + ENZA group, ibPFS significantly increased in HRR-deficient patients (HR, 0.46; 95% CI, 0.30-0.70; P 0.001), HRR-non-deficient or unknown patients (HR, 0.70; 95% CI, 0.54-0.89; P= 0.004), and HRR-non-deficient patients by tumor tissue testing (HR, 0.66; 95% CI, Overall survival statistics are still developing; 30.6% of TALA and 32.0% of PBO patients had passed away; the TALA + ENZA arm had a higher HR (0.89 [95% CI, 0.69-1.14; P= 0.35]).
The TALA + ENZA vs. PBO + ENZA arm substantially outperformed the PBO + ENZA arm in terms of objective response rates, PSA response, time to PSA progression, use of subsequent cytotoxic chemotherapy, and antineoplastic therapy. Grade 3–4 treatment-emergent adverse events occurred in patients at a rate of 71.9% (TALA + ENZA) and 40.6% (PBO + ENZA) (TEAEs). Anemia, poor neutrophil and platelet counts, and fatigue were the most prevalent grade 3 TEAEs in both groups.
The incidence of ENZA discontinuation was 10.8% in the TALA + ENZA arm versus 11.0% in the PBO + ENZA arm. There were no new warnings for safety, and toxicity was usually under control.
Source: https://meetings.asco.org/abstracts-presentations/216877
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03395197
Agarwal, N., Azad, A., Carles, J., Fay, A. P., Matsubara, N., Heinrich, D., Szczylik, C., Giorgi, U. D., Joung, J. Y., Fong, P. C. C., Voog, E., Jones, R. J., Shore, N. D., Dunshee, C., Zschaebitz, S., Lin, X., Healy, C. G., Santo, N. D., Zohren, F. & Fizazi, K. (2023). J Clin Oncol 41, 2023 (suppl 6; abstr LBA17) DOI: 10.1200/JCO.2023.41.6_suppl.LBA17
