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Highlights from the 2024 ASCO Genitourinary Cancers Symposium |
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| CONTACT-02: Phase 3 Study of Cabozantinib + Atezolizumab vs Second Novel Hormonal Therapy in Patients with mCRPC
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| Neeraj Agarwal, MD
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| The CONTACT-02 phase 3 study, presented by Neeraj Agarwal at the 2024 ASCO GU annual meeting, investigated cabozantinib + atezolizumab versus a second novel hormonal therapy in metastatic castration-resistant prostate cancer patients who had progressed on a prior novel hormonal therapy and had extrapelvic nodal or visceral metastasis. The trial showed that cabozantinib + atezolizumab significantly improved radiographic progression-free survival compared to the control arm.
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| BRCAAway: A Randomized Phase 2 Trial of Abiraterone, Olaparib, or Abiraterone + Olaparib in Patients with mCRPC Bearing HRR Mutations
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| Maha H. A. Hussain, MD
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| Maha Hussain presented the BRCAAway trial which aimed to assess the efficacy of AR inhibitor versus PARP inhibitor versus combination in first-line mCRPC patients with BRCA1/2 or ATM mutations. The combination arm (olaparib + abiraterone/prednisone) demonstrated longer progression-free survival compared to either agent alone or sequentially. The front-line combination had better PFS compared to sequential therapy.
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| Safety Outcomes in Patients with mCRPC Treated with Radium-223 Following External Beam Radiation Therapy: REASSURE US Subset
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| Oliver Sartor, MD
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| Oliver Sartor presented on the REASSURE study discussing safety outcomes in mCRPC patients treated with radium-223 after external beam radiation therapy. Dr. Sartor delves into the findings, emphasizing manageable toxicities and a reasonable safety profile.
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| Intensification of ADT with Enzalutamide in High-Risk Patients with Biochemical Relapse Following Radical Prostatectomy Undergoing Salvage Radiation: Initial Results from RTOG 3506 (STEEL) |
| Edwin Posadas, MD, FACP |
| The STEEL (RTOG 3506) study explores treatment intensification with enzalutamide in combination with ADT for high-risk patients with biochemical relapse after radical prostatectomy undergoing salvage radiotherapy. The initial results showed a non-significant trend towards improved progression-free survival with enzalutamide, and while there was a slight increase in grade 3 and 4 adverse events, the overall toxicity was manageable. |
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| Phase 1 Results and Phase 2 Design - Oral Epi-7386 (Masofaniten) in Combination With Enzalutamide Compared to Enzalutamide Alone in Patients with mCRPC |
| Christos Kyriakopoulos, MD |
| Christos Kyriakopoulos discussed the phase 1/2 trial focusing on the combination of oral EPI-7386 with enzalutamide compared to enzalutamide alone in metastatic castration-resistant prostate cancer patients. The study demonstrated a well-tolerated safety profile during the phase 1 portion, with promising efficacy outcomes observed, including high PSA response rates. |
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| Enfortumab Vedotin as Monotherapy in Patients with mCRPC: Results of Stage I of a Phase 2 Trial
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| Umang Swami, MD, MS
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| This phase 2 trial evaluating enfortumab vedotin as monotherapy in mCRPC showed promising efficacy and an acceptable safety profile. Of the 11 patients in stage 1, 7 demonstrated a protocol-defined response, including PSA 50% responses, objective responses, confirmed circulating tumor cell responses, and sustained treatment duration. The median radiographic progression-free survival was 5.5 months, and adverse events were manageable, with no Grade 5 events reported. Further enrollment in stage 2 of the trial is ongoing.
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| Enzalutamide Combination Treatment Suspension in Men with High-Risk Biochemically Recurrent Prostate Cancer: Outcomes from EMBARK |
| Stephen Freedland, MD |
| Stephen Freedland presented a post-hoc analysis of the EMBARK trial, enzalutamide combination treatment suspension in men with high-risk biochemically recurrent prostate cancer showed improved MFS compared to leuprolide alone. The analysis suggests that enzalutamide combination benefits patients who suspend treatment, with higher rates of undetectable PSA levels after 2 years. |
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| CYPIDES Phase 2 Results MK-5684 (ODM-208), a CYP11A1 Inhibitor, in Patients with mCRPC with and without AR-LBD Mutations |
| Karim Fizazi, MD, Ph.D. |
| Karim Fizazi presented the CYPIDES phase 2 trial of MK-5684 (ODM-208), a CYP11A1 inhibitor, which demonstrated promising antitumor activity in metastatic castration-resistant prostate cancer patients. The treatment was well-tolerated, with adrenal suppression-related adverse events being the most common. The findings suggest potential efficacy of MK-5684 in heavily pre-treated mCRPC patients, particularly those with activating AR-LBD mutations. |
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| Efficacy of Olaparib plus Abiraterone Versus Placebo plus Abiraterone in Patients with mCRPC with Single Homologous Recombination Repair Gene Mutations in the PROpel Trial
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| Neal Shore, MD, FACS
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| In the PROpel trial, a post-hoc analysis evaluated the efficacy of olaparib plus abiraterone acetate/prednisone versus placebo plus abiraterone acetate/prednisone in patients with mCRPC and single homologous recombination repair gene mutations. The analysis revealed that for most patients with a single gene HRR mutation, there was both an improvement in radiographic progression-free survival and overall survival with the addition of olaparib to abiraterone.
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| Overall Survival with Darolutamide Versus Placebo in Combination with Androgen Deprivation Therapy and Docetaxel: A Sensitivity Analysis from ARASENS Accounting for Subsequent Therapy
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| Neal Shore, MD, FACS
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| Neal Shore presented the post hoc sensitivity analysis from ARASENS, evaluating the overall survival benefit of darolutamide versus placebo in combination with ADT and docetaxel for mHSPC. The analysis, which counted initiation of subsequent systemic antineoplastic therapy as an event in censored patients, along with planned sensitivity analyses, consistently supported the primary OS analysis results.
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| Exploratory Analyses of Homologous Recombination Repair Gene Subgroups and Potential Associations with Secondary Efficacy Endpoints in the HRR-Deficient Population from TALAPRO-2 |
| Stefanie Zschaebitz, MD |
| The exploratory analyses of HRR gene subgroups in the HRR-deficient population from TALAPRO-2 revealed a broad and pronounced efficacy benefit for talazoparib + enzalutamide compared to placebo + enzalutamide across multiple molecular subgroups. The most significant benefits were observed for the BRCA1-PALB2-BRCA2 axis and CDK12. The differential efficacy was evident in various endpoints, including objective response rate, time to progression or death on first subsequent antineoplastic therapy, PSA response ≥50%, time to PSA progression, and time to initiation of cytotoxic chemotherapy. |
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| Evaluating Early Changes in Circulating Tumor DNA Tumor Fraction as a Value Add to PSA in Predicting Early Progression in mCRPC |
| Christopher Sweeney, MBBS |
| Chris Sweeney presented an analysis of IMbassador250. The study used FoundationOne Monitor to monitor ctDNA, and the analysis included 418 patients. Detection of tumor fraction at cycle 3, day 1 was associated with significantly worse radiographic progression-free survival and overall survival. The positive predictive value of ctDNA status for predicting a non-durable response was higher than that of PSA. The study suggests that ctDNA monitoring complements PSA testing, providing additional information for a personalized approach in mCRPC patients. |
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| Homologous Recombination Repair Gene Mutation Testing Patterns and Treatment Selection from a Real-World Cohort of Patients with mCRPC
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| Neal Shore, MD, FACS
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| The real-world analysis by Neal Shore focused on homologous recombination repair gene mutation testing patterns and treatment selection in metastatic castration-resistant prostate cancer patients. The study, covering 996 patients, revealed that around 60% of patients received testing for HRR mutations, with testing rates increasing following the approval of PARP inhibitors.
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| Interaction of Age and Benefit of Treatment Intensification in Advanced Prostate Cancer: An Aggregate Meta-Analysis of 14 Randomized Trials
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| Alicia K. Morgans, MD, MPH
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| Alicia Morgans presented a study exploring the interaction between age and the benefit of treatment intensification in advanced prostate cancer. Treatment intensification significantly improved overall survival, but the study found a significant interaction between age and treatment intensification, with younger men deriving more substantial benefits compared to older men.
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