Correlation between time to PSA progression (TTPP), radiographic progression-free survival (rPFS) and overall survival (OS) in first-line abiraterone/enzalutamide (Abi/Enza) and docetaxel (Doc) treated patients in a prospective cohort study.

Abstract

267 Background: Abiraterone, enzalutamide and docetaxel represent first-line (1L) treatment options in mCRPC. A significant correlation between rPFS and OS has been reported for patients treated with 1L abi and enza in mCRPC. It is however unclear whether TTPP or rPFS present a similar magnitude of correlation with OS in Doc-treated pts. Methods: We evaluated the association of TTPP and rPFS with OS in pts treated with 1L Abi/Enza or Doc in a prospective multicenter observational cohort study. TTPP and rPFS were defined as per PCWG2. Correlation between TTPP and rPFS with OS was evaluated with Spearman rho coefficients (r), and by calculating the concordance index (c-index) in Cox-regression models. Results: 406 out of 419 pts received 1L Abi/Enza or Doc. After a median follow-up of 40 months (m), 253 mCRPC-related deaths were observed, with a median OS of 31.3 m (95% CI: 27.6-35). Median rPFS and TTPP were 10.8 m (95% CI:9.7-11.9) and 7.2 m (95% CI:6.7-7.7), respectively. Significant correlations between rPFS/TTPP and OS were observed in all pts treated at 1L, as well as in Abi/Enza and Doc treated pts (Table). R and c-index were consistently higher in Abi/Enza treated pts than in Doc treated pts, with a higher difference in predictive accuracy of the Cox regression model observed when comparing the association between TTPP and OS (c-index 0.788 in Abi/Enza treated pts vs 0.627 in Doc treated pts). Conclusions: Differences in r and c-index were observed when evaluating the association between TTPP/rPFS and OS in Abi/Enza and Doc treated pts, suggesting rPFS and TTPP may better predict OS in Abi/Enza than in Doc-treated pts. Indirect comparisons of TTPP in Abi/Enza vs Doc pts may therefore not reflect their true impact on OS. Further insight on the exact significance of TTPP is needed. Clinical trial information: NCT03075735. [Table: see text]

Comparison of Radiographic Progression-Free Survival and PSA Response on Sequential Treatment Using Abiraterone and Enzalutamide for Newly Diagnosed Castration-Resistant Prostate Cancer: A Propensity Score Matched Analysis from Multicenter Cohort

“…As expected, both rPFS and TTPP were significantly correlated with OS ( p < 0.001 in both rPFS and TTPP). Importantly, higher SCC in rPFS was observed compared to that in TTPP (0.601 in rPFS vs 0.468 in TTPP), indicating rPFS is a robust surrogate for predicting OS, which is consistent with the previous report by Lorente et al [31].…”

“…Several post-hoc studies from the results of randomized control trials (RCTs) revealed emerging evidence that radiographic progression-free survival (rPFS) is highly correlated with overall survival (OS), potentially serving as an indicator of treatment outcome in CRPC patients [29,30,31]. In 2015, Morris et al first reported that the Spearman’s correlation coefficient (SCC) between rPFS and OS was 0.71 (95%CI: 0.65–0.77) in pot-hoc analysis from COU-AA-302 study (abiraterone vs placebo for chemotherapy-naïve metastatic CRPC) [30].…”

“…Subsequently, Rathkopf et al showed similar SCC between rPFS and OS (SCC: 0.72, 95%CI: 0.67–0.76) from the PREVAIL study (enzalutamide vs placebo for chemotherapy-naïve metastatic CRPC) [29]. Recently, the results from a prospective multicenter observational cohort study in 406 metastatic CRPC patients treated with ASIs or docetaxel as a first line (NCT03075735) demonstrated Pearson’s correlation with OS of 0.65 in rPFS and 0.54 in TTPP [31]. In the present study, we conducted propensity score-matched analysis for the treatment of newly diagnosed CRPC patients treated with sequential ASIs from the first line, and assessed rPFS as well as PSA response in each line to investigate the extent of cross-resistance with these ASIs and the impacts on their prognosis.…”

Niraparib and Abiraterone Acetate (Akeega)

“…This is because the emphasis on radiographic results to determine disease progression and treatment benefit in the mCRPC setting does not adequately reflect clinical practice, which involves a broader and more holistic assessment of determining treatment benefit. While there are data emerging that rPFS is a predictor of OS, [54][55][56] CADTH reviewers concluded that the association was difficult to interpret at the time of this review because of the varying definitions of rPFS used, relatively short follow-up periods used for the comparisons, and lack of prospective evidence. The clinical experts agreed that given the advancements in therapies and understanding of the natural history of prostate cancer, OS remains the most clinically relevant outcome.…”