Nobuaki Matsubara1, Kim N Chi2, Mustafa Özgüroğlu3, Alfredo Rodriguez-Antolin4, Susan Feyerabend5, Luis Fein6, Boris Y Alekseev7, Giri Sulur8, Andrew Protheroe9, Susan Li10, Suneel Mundle11, Peter De Porre12, Namphuong Tran8, Karim Fizazi13. 1. National Cancer Center Hospital East, Chiba, Japan. Electronic address: nmatsuba@east.ncc.go.jp. 2. BC Cancer Agency, Vancouver, BC, Canada. 3. Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey. 4. 12 de Octubre University Hospital, Madrid, Spain. 5. Studienpraxis Urologie, Nürtingen, Germany. 6. Instituto de Oncologia de Rosário, Rosário, Argentina. 7. P.A. Hertsen Moscow Cancer Research Institute, Moscow, Russian Federation. 8. Janssen Research & Development, Los Angeles, CA, USA. 9. Oxford University Hospitals Foundation NHS Trust, Oxford, UK. 10. Janssen Research & Development, Spring House, PA, USA. 11. Janssen Research & Development, Raritan, NJ, USA. 12. Janssen Research & Development, Beerse, Belgium. 13. Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
Abstract
BACKGROUND: LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC). OBJECTIVE: To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS). DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT). RESULTS AND LIMITATIONS: AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p < 0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p < 0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS. CONCLUSIONS: Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC. PATIENT SUMMARY: We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.
RCT Entities:
BACKGROUND: LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC). OBJECTIVE: To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS). DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT). RESULTS AND LIMITATIONS: AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p < 0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p < 0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS. CONCLUSIONS: Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC. PATIENT SUMMARY: We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.
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