Niranjan J Sathianathen1, Samantha Koschel2, Isaac A Thangasamy2, Jiasian Teh2, Omar Alghazo2, Georgiana Butcher3, Harriet Howard3, Jada Kapoor2, Nathan Lawrentschuk1, Shankar Siva4, Arun Azad5, Ben Tran6, Damien Bolton7, Declan G Murphy8. 1. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; Department of Surgery, Austin Health, The University of Melbourne, Parkville, Victoria, Australia. 2. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia. 3. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; University of Sheffield Medical School, Sheffield, UK. 4. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. 5. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia. 6. Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia. 7. Department of Surgery, Austin Health, The University of Melbourne, Parkville, Victoria, Australia. 8. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. Electronic address: declan.murphy@petermac.org.
Abstract
CONTEXT: There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy. OBJECTIVE: To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. EVIDENCE ACQUISITION: We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease. EVIDENCE SYNTHESIS: We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons. CONCLUSIONS: Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients. PATIENT SUMMARY: Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.
CONTEXT: There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy. OBJECTIVE: To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. EVIDENCE ACQUISITION: We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease. EVIDENCE SYNTHESIS: We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons. CONCLUSIONS: Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients. PATIENT SUMMARY: Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.
Authors: Niranjan J Sathianathen; Makinna C Oestreich; Sarah Jane Brown; Shilpa Gupta; Badrinath R Konety; Philipp Dahm; Frank Kunath Journal: Cochrane Database Syst Rev Date: 2020-12-12