Comparative Analysis Of Systemic Therapy For Metastatic Hormone-sensitive Prostate Cancer

Objective: Multiple Phase III clinical studies have demonstrated that novel androgen inhibitors and/or chemotherapy agents in combination with androgen deprivation therapy(ADT)are effective regimens for the treatment of metastatic hormone-sensitive prostate cancer(m HSPC).But which combination therapy has the greater survival benefit and least adverse effects is unclear.This study was aimed to determine the efficacy and safety of different combination therapies in the treatment of m HSPC,and to observe the therapeutic effects of novel endocrine drugs apalutamide and abiraterone and bicalutamide in the real-world clinical environment,hoping to provide ideas for the clinical selection of systemic treatment of m HSPC.Methods: This study first included 12 Phase III clinical trials of novel endocrine agents and/or chemotherapy agents for m HSPC patients by searching the literature.R software was used to indirectly compare the Overall survival(OS),progression-free survival(PFS)and adverse event rate of m HSPC patients treated with triple-therapy or dual-therapy through Bayesian network meta-analysis.And the treatment the curative effect of subgroups in high and low-volume were analyzed.Clinical data and followup data of newly diagnosed m HSPC patients treated with apalutamide or abiraterone or bicalutamide combined with ADT as first-line therapy were collected from the Second Hospital of Lanzhou University,Gansu Provincial People’s Hospital and Gansu Provincial Cancer Hospital from January 2018 to March 2023.Compared with prostate specific antigen(PSA)response after 3 months treatment and objective response rate(ORR)during follow-up,as well as treatment-related adverse events in these three groups,The therapeutic effects of high and low-volume and Gleason score subgroups were compared and analyzed.Results: Totally 10629 patients were involved in this network meta-analysis.Triple-and dual-therapies were associated with significantly improved OS and PFS compared with ADT.Darolutamide + docetaxel +ADT(HR=0.54,95%CI 0.39-0.76;comprehensive rank=0.89)emerged as the best option of OS,and abiraterone+prednisolone+ docetaxel+ ADT(HR=0.33,95%CI 0.19-0.53;comprehensive rank=0.92)emerged as the best option of PFS.In the high-volume subgroup,triple-therapy also remained the best regimen in prolonging OS and PFS compared with the ADT.In the low-volume subgroup,apalutamide+ ADT may be the best choice in terms of OS and PFS.In all efficacy related comparisons,combination therapies including novel androgen signaling inhibitors,were more effective than docetaxel+ ADT.As for adverse events,apalutamide+ ADT had the lowest odds of all and ≥3 grades adverse events.Triple-therapies had the highest incidence rates of all and ≥3 grades adverse events.In this study,a retrospective analysis of 143 newly diagnosed m HSPC patients was conducted in real-world observation.The results indicated that the novel endocrine drugs apalutamide and abiraterone were superior to the traditional endocrine drug bicalutamide in terms of prolongation of PFS,prophase PSA response to nadir prostate specific antigen(n PSA)after 3 months medication and ORR during follow-up,and the effect of apalutamide was superior to abiraterone.Multivariate COX regression analysis suggested that the use of different systemic treatments and the Eastern cooperative oncology group(ECOG)score and whether n PSA was achieved during follow-up were independent predictors of PFS.PFS were longer in the apalutamide group than in the abiraterone and bicalutamide groups in the high-volume subgroup,there was no difference between the abiraterone group and bicalutamide group.However,both of the novel endocrine drugs were still superior to bicalutamide in their ability to decrease PSA after 3 months of application and ORR during follow-up.In the low-volume subgroup,PFS of the two novel endocrine drugs were both longer than those of the bicalutamide group,the apalutamide group had no special advantage in PFS compared with the abiraterone group.The apalutamide group had the highest number of n PSA after 3 months of treatment in the low-volume subgroup,and the highest ORR during follow-up.In the Gleason≥8 subgroup,PFS and other observations were consistent with the overall results.Not only were the novel endocrine drugs apalutamide and abiraterone superior to bicalutamide,but apalutamide also showed a tendency to be superior to abiraterone.In Gleason≤7 subgroup,there was no difference among the three treatment regiments in each observation index.In terms of safety,there was no significant difference in the incidence of all and ≥3 grades adverse events among the three groups.Conclusions: The results of the network meta-analysis suggested that tripletherapies were better than dual-therapies for the long-term survival of m HSPC patients,and the analysis of the high-volume subgroup also suggested that triple-therapies were better than dual-therapies in the prolongation of OS and PFS,but triple-therapies also had a higher incidence of adverse events.The long-term efficacy of combination therapy involving novel endocrine drugs was better than that of chemotherapy combined with ADT.Apalutamide +ADT was associated with the lowest incidence of adverse events among all treatments,and may also be the most effective treatment for the low-volume subgroup.Real world clinical observation results suggest that the clinical efficacy of novel endocrine drugs apalutamide and abiraterone is better than that of bicalutamide,and the effect of apalutamide is more significant.There was a consistent trend between the high and low-volume subgroup and Gleason≥8 subgroup,but no significant difference was observed in Gleason≤7 subgroup.The incidence of adverse events was similar among the three treatment regimens.