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PEER-TO-PEER CLINICAL CONVERSATIONS |
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| Emerging DLL3-Targeted Therapies Demonstrate Efficacy in Neuroendocrine Prostate Cancer |
| Himisha Beltran, MD |
| Himisha Beltran discuses DLL3, a promising target for neuroendocrine prostate cancer treatment. Dr. Beltran explains that DLL3 is highly expressed in neuroendocrine and small cell prostate cancers, making it an attractive therapeutic target. |
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| T-Cell Engagers in Prostate Cancer Treatment |
| Neeraj Agarwal, MD, FASCO |
| Alicia Morgans interviews Neeraj Agarwal about his presentation on T-cell engaging treatments for prostate cancer. Dr. Agarwal discusses the rationale behind T-cell engagers, their potential to bypass the limitations of prostate cancer's cold tumor microenvironment, and the various tumor-associated antigens being targeted. |
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| INSPIRE Trial Investigates Immunotherapy for Molecularly Selected Advanced Prostate Cancer |
| Niven Mehra, MD, PhD |
| Neeraj Agarwal interviews Niven Mehra about the INSPIRE trial. The study examines the efficacy of nivolumab and ipilimumab combination therapy in molecularly selected patients with metastatic castration-resistant prostate cancer (mCRPC). |
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| Results from the Quick Efficacy Seeking Trial (QuEST1) Arm Combining BN-Brachyury (BNVax) + Bintrafusp Alfa + Nogapendekin Alfa Inbakicept-Pmln (N-803) in Castration-Resistant Prostate Cancer |
| Jason M. Redman, MD |
| The QuEST1 trial investigated a three-drug immunotherapy combination (BN-brachyury vaccine, bintrafusp alfa, and N-803) in CRPC. Among 24 evaluable patients, 29% achieved a PSA response, including two mismatch repair proficient patients with partial responses. The 6-month progression-free survival was 35%, and the 3-year overall survival was 67%. While the toxicity profile aligned with individual agents, a notable incidence of adrenal insufficiency was observed exclusively in responders, warranting further research into its potential role in treatment efficacy. |
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| INSPIRE: Phase 2 Trial of Nivolumab 3mg/kg and Ipilimumab 1mg/kg in Molecularly Selected Patients with mCRPC |
| Niven Mehra, MD |
| The phase II INSPIRE trial evaluated nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) in molecularly selected metastatic castration-resistant prostate cancer (mCRPC) patients. The study demonstrated a disease control rate of >6 months in 38% of patients, with the highest efficacy in those with mismatch repair deficiency (81% disease control, 32.7-month median progression-free survival). While responses were limited in hTMB, CDK12i, and BRCA mutation groups, findings emphasize early testing and precision medicine approaches for mismatch repair-deficient mCRPC. |
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| Xaluritamig, a STEAP1 x CD3 XmAb 2+1 Immune Therapy, in Patients With Metastatic Castration-Resistant Prostate Cancer: Initial Results From Dose Expansion Cohorts in a Phase 1 Study |
| William Kelly, DO |
| William Kelly presents results from a Phase 1 study exploring Xaluritamig, a STEAP1 x CD3 bispecific XmAb 2+1 T-cell engager, in patients with metastatic castration-resistant prostate cancer (mCRPC). STEAP1 is a highly expressed antigen in prostate cancer, present in over 80% of mCRPC cases and associated with poor prognosis. |
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| Combination of PARP Inhibitors and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer - Beyond the Abstract |
| Louise Kostos, and Arun A. Azad, MBBS, PhD, FRACP |
| Combination therapies involving PARP inhibitors and androgen receptor pathway inhibitors in mCRPC exploit synergistic mechanisms, such as synthetic lethality and mutual suppression of DNA repair and AR pathways. Phase 3 trials (PROpel, MAGNITUDE, and TALAPRO-2) demonstrate the greatest benefit in BRCA-mutant patients, moderate efficacy in broader HRR-mutated populations, and limited impact in non-HRR-mutated cases. |
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Olaparib plus Abiraterone Versus Placebo plus Abiraterone in Metastatic Castration-Resistant Prostate Cancer (PROpel): Final Prespecified Overall Survival Results of a Randomised, Double-Blind, Phase 3 Trial - Beyond the Abstract
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| Fred Saad, MD, FRCS, Noel Clarke, MBBS, FRCS, ChM, FRCS, Mototsugu Oya, MD, and Andrew J. Armstrong, MD, MSc |
| The PROpel trial evaluated olaparib combined with abiraterone versus placebo plus abiraterone as a first-line treatment for mCRPC, regardless of homologous recombination repair mutation status. The combination significantly improved radiographic progression-free survival compared to the placebo group and showed a numerical improvement in overall survival by 7.4 months, though this did not reach statistical significance. |
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