PSA-progression only in high-risk, metastatatic hormone-sensitive prostate cancer patients treated with abiraterone in the LATITUDE trial.

Abstract

102 Background: The LATITUDE (NCT01715285) trial established the survival benefit of abiraterone (AA) over placebo (PBO) in combination with ADT as first-line therapy in high-risk mHSPC patients. By PCWG3 guidelines, pts with PSA progression and no clinical or radiographic progression should not discontinue therapy. We aimed to evaluate the proportion of patients experiencing PSA progression only in the LATITUDE trial and its prognostic significance. Methods: We performed a retrospective, post-hoc analysis of pts treated in the LATITUDE trial (YODA project #2020-4298). Confirmed PSA progression (PSAProg) and radiographic progression (RadProg) were defined by PCWG2 criteria. Patients with PSA progression with a coinciding radiographic evaluation showing no radiographic progression were defined as progressing by PSA only. In these patients, time from PSA to radiographic progression was defined as the time (months) from the date of confirmed PSAProg to the date of RadProg. Kaplan-meier and Cox models were used to define median survival times and comparison of outcomes in the AA vs PBO groups. Results: 771 patients (63.7%) experienced PSAProg; AA: 302 pts (49.9%); PBO: 469 pts (77.6%). In 501 pts (64.5%) there was no RadProg on the coinciding radiographic evaluation (PSA only progression), 187 (61.9%) in the AA and 314 (67%) in the PBO arm (p = 0.153). 207 (41.3%) pts had measurable disease at baseline, a similar proportion to that in the overall study population (43.8%). 315 (62.9%) of pts with PSA progression only developed subsequent radiographic progression, 105 (56.1%) in the AA and 210 (66.9%) in the PBO arm (p = 0.017). Median time from PSAProg to RadProg was 8.4 months (95%CI: 8.1-9.2); no significant difference was observed in pts in the AA vs PBO arm (9.2 vs 8.3 months; HR: 0.88 [95%CI: 0.7-1.1]; p = 0.287). Median OS from the time of PSAProg was 19.8 months (95%CI:17.2-24) in AA-treated pts. OS from time to PSAProg was longer in AA-treated pts with PSAonly progression than those with simultaneous PSAProg & RadProg (24 vs 15.3 months; HR: 0.62; p = 0.007). Conclusions: A significant proportion of high-risk mHSPC patients experience a PSA rise as the only initial feature of disease progression. In these patients, there appears to be no significant difference in time from PSA to radiographic progression in AA vs PBO treated-patients. These results highlight the need to ensure an appropriate follow-up in pts progressing by PSA, in order to identify radiographic or clinical progression and initiate subsequent therapy early, thereby maximizing benefit from the treatment sequence.