He, Huan

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide evidence-based recommendations for patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS An Expert Panel including patient representation completed a systematic review of the evidence and made recommendations. RESULTS Depending upon prior treatment received, androgen receptor pathway inhibitors (ARPIs: enzalutamide, abiraterone with prednisone), poly(ADP-ribose) polymerase inhibitors (PARPi), chemotherapeutic agents (docetaxel, cabazitaxel), radiopharmaceuticals (radium 223, 177 Lu-prostate-specific membrane antigen [PSMA]-617), and sipuleucel-T have demonstrated an overall survival (OS) benefit for patients with mCRPC. For patients with BRCA1 / 2 alterations who did not receive prior ARPI, the combination of PARPi and ARPI (talazoparib + enzalutamide, olaparib and/or niraparib + abiraterone) has shown clinical benefit. For patients with BRCA1 / 2 alterations who received prior ARPI or ARPI followed by docetaxel, olaparib showed OS benefit. In select patients with microsatellite instability-high/mismatch repair-deficient, pembrolizumab showed clinical efficacy. RECOMMENDATIONS Prior systemic therapy for castration-sensitive prostate cancer will determine subsequent therapy used for mCRPC. Continue androgen-deprivation therapy for patients with mCRPC indefinitely. Early adoption of somatic genetic testing and palliative care is recommended. Patients with mCRPC and bony metastases should receive a bone-protective agent. The panel recommends the combination of ARPI with PARPi in patients with BRCA1 / 2 alterations who did not receive prior ARPI. For patients who received prior ARPI, the panel recommends docetaxel chemotherapy. The panel recommends 177 Lu-PSMA-617 or cabazitaxel chemotherapy for patients who receive prior ARPI and docetaxel chemotherapy. For patients with BRCA1 / 2 alterations who received prior ARPI, the panel recommends PARPi monotherapy. Radium 223 is recommended for patients with symptomatic bone–only disease. Evidence for optimal sequencing for mCRPC regimens is lacking. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .

e24070 Background: We have maintained a living interactive systematic review (LISR) on the treatment of CAT ( CAT LISR ). Recent publications of CASTA-DIVA and CANVAS trials prompted this report of updated analysis. Methods: The approach to creating LISRs has been previously published and is available on our website. ( LIvE synthesis framework ). Patient important outcomes included venous thromboembolism (VTE) recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), net clinical benefit (NCB) and all-cause mortality. Mantel-Haenszel method was used to pool treatment effect estimates. A Paul-Mendel random-effects meta-analysis was conducted to compare DOACs with LMWH. Mixed-treatment comparisons were computed using fixed-effect model within a Bayesian framework owing to a sparse and open network. Effect estimates were expressed as odds ratio (OR) with 95% confidence intervals (CI). Surface under the cumulative ranking curve (SUCRA) was used to assess relative treatment rankings. Results: This systematic review currently includes six RCTs with a total of 3690 patients and four unique treatment choices. Apixaban was assessed in two trials (ADAM-VTE, CARAVAGGIO), rivaroxaban in two (SELECT-D, CASTA-DIVA) and edoxaban in one (HOKUSAI-VTE). CANVAS trial reported efficacy of DOACs as a class and hence, was only included in direct comparisons with LMWH. Direct comparisons showed that DOACs as a class significantly decreased the odds of VTE recurrence (OR 0.63, 95% CI: 0.49-0.82) without significantly increasing major bleeding (OR 1.23, 95% CI: 0.84-1.79) when compared to LMWH. However, higher odds of CRNMB (OR 1.65, 95% CI: 1.18-2.31) was observed with DOACs when compared to LMWH. Mortality rates were not different between the two groups (OR: 1.03, 95% CI: 0.87-1.21). Mixed treatment comparisons showed decreased VTE recurrences with rivaroxaban (rank 1; OR 0.49, 95% CI: 0.23-0.99) and apixaban (rank 2; OR 0.58, 95% CI: 0.36-0.90) relative to LMWH (rank 4). No significant differences were observed between edoxaban (rank 3) and LMWH in terms of VTE risk reduction. Edoxaban (rank 4) increased the risk of major bleeding (OR 1.77, 95% CI: 1.05-3.15) compared to LMWH (rank 2); there were no significant differences among rivaroxaban (rank 3) apixaban (rank 1), and LMWH. Rivaroxaban (rank 4; OR 3.16; 95% CI: 1.61-6.68) and apixaban (rank 3; OR 1.51, 95% CI: 1.01-2.28) increased the risk of CRNMB compared to LMWH (rank 1). Significant net clinical benefit was observed with apixaban (rank 1; OR 0.66; 95% CI: 0.46-0.94) when compared to LMWH (rank 4). No significant differences were observed among other mixed treatment comparisons. Conclusions: Patients treated with DOACs have 31 fewer VTE events per 1000 CAT patients compared to LMWH. Amongst DOACs, apixaban offers the greatest net clinical benefit with 39 fewer VTE and MB events per 1000 patients compared to LMWH.