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HIGHLIGHTS FROM THE 2024 EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY ANNUAL MEETING
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| SPLASH Trial Highlights Radiopharmaceutical Lutetium-177’s Role in Advanced Prostate Cancer Treatment |
| A. Oliver Sartor, MD |
| Oliver Sartor discusses the SPLASH trial results, evaluating Lutetium-177-PNT2002 in metastatic castration-resistant prostate cancer patients who progressed on ARPI therapy. The study shows significant improvement in radiographic progression-free survival for Lutetium-177-PNT2002 compared to alternate ARPI therapy, with a hazard ratio of 0.71. |
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| Proffered Paper Session: GU Tumours, Prostate |
| Efficacy of 177Lu-PNT2002 in PSMA-Positive mCRPC Following Progression on an Androgen-Receptor Pathway Inhibitor (SPLASH)
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| A. Oliver Sartor, MD
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| Oliver Sartor presents interim results from the SPLASH trial, showing that 177Lu-PNT2002 significantly improves radiographic progression-free survival compared to an alternate ARPI in PSMA-positive mCRPC patients, with a median of 9.5 vs. 6 months. The treatment also demonstrated higher response rates and better quality of life, although overall survival data is still maturing.
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| UpFrontPSMA : A Randomized Phase II Study of Sequential 177Lu-PSMA-617 and Docetaxel versus Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer |
| Arun Azad, PhD, MBBS, FRACP |
| Arun Azad presents the UpFrontPSMA trial, revealing that sequential 177Lu-PSMA-617 plus docetaxel significantly improved undetectable PSA rates at 48 weeks and PSA progression-free survival compared to docetaxel alone in metastatic hormone-sensitive prostate cancer. The combination therapy showed promising results without increased toxicity, suggesting a potential new role for 177Lu-PSMA-617 in treatment. |
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| Invited Discussant: Efficacy of SPLASH and UpFrontPSMA Trials |
| Irene Burger, MD
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| Irene Burger discusses the SPLASH and UpFrontPSMA trials, highlighting key comparisons and findings. The SPLASH trial with 177Lu-PNT2002 showed a moderate benefit in rPFS compared to the PSMAfore trial with 177Lu-PSMA-617, which had a more pronounced benefit but with higher doses. In the UpFrontPSMA trial, sequential 177Lu-PSMA-617 combined with ADT and docetaxel showed comparable rPFS to abiraterone in de novo high-volume metastatic prostate cancer but had a more favorable safety profile. |
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| What’s on The Horizon for Metastatic Prostate Cancer Patients? |
| B7-H3 as Therapeutic Target for Prostate Cancer
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| Juliet Carmichael, MD
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| Juliet Carmichael highlights B7-H3 as a promising therapeutic target for prostate cancer, noting its frequent overexpression in castrate-resistant prostate cancer (CRPC) and association with DNA repair defects. Despite B7-H3's high expression in most CRPC cases and its potential as a therapeutic target, its exact role in tumor growth remains unclear.
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| DLL-3 Targeted Therapy for Neuroendocrine Prostate Cancer |
| Himisha Beltran, MD |
| Himisha Beltran discusses Delta-like ligand 3 (DLL3) as a potential target for neuroendocrine prostate cancer, noting its increased expression in this aggressive cancer type compared to standard prostate cancer. While DLL3-targeted therapies like Tarlatamab showed limited efficacy in early trials, newer approaches such as DLL3-targeting T cell engagers and imaging agents are under development, with promising results from recent studies. |
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| T Cell Engagers in Prostate Cancer |
| Neeraj Agarwal, MD |
| Neeraj Agarwal discusses the evolving role of T-cell engagers in prostate cancer therapy, specifically targeting the immunologically "cold" nature of metastatic castration-resistant prostate cancer. Prostate cancer's immune environment is challenging due to factors like loss of PTEN, reduced MHC expression, and low tumor mutational burden, which limit the effectiveness of conventional immunotherapies. |
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| Abstracts/Posters |
| Total and Regional Changes in Body Composition in Metastatic Hormone-Sensitive Prostate Cancer Patients Randomized to Receive Androgen Deprivation + Enzalutamide +/- Zoledronic Acid. the BonEnza Study
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| Martina Buffoni, MD |
| The BonEnza study found that in metastatic hormone-sensitive prostate cancer patients treated with ADT and enzalutamide, there was a significant increase in fat body mass and a decrease in lean body mass after 18 months. Changes in body composition were heterogeneous across different regions of the body, with younger patients experiencing a more pronounced increase in fat mass.
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| Factors Influencing Clinical and Biological Response in Patients Treated with [177Lu]Lu-PSMA-617 Under France's Early Access Program
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| Vincent Habouzit, MD, MSc
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| Vincent Habouzit presented data from a French nationwide study evaluating the clinical and biological responses to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer patients. The study found that 44.5% of patients responded positively to the treatment, with factors such as complete PSMA lesion positivity, receipt of all planned treatment cycles, and concomitant ARPI or bisphosphonate use associated with better outcomes.
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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 |
| Jason Redman presents the final results from the QuEST1 trial evaluating the combination of BN-brachyury (BNVax), bintrafusp alfa, and N-803 in CRPC. The combination therapy showed promising activity, with 29% of evaluable patients achieving PSA responses, including partial responses in some mismatch repair proficient individuals. Notably, the treatment was associated with a higher incidence of adrenal insufficiency in responders, suggesting a need for further investigation into its immune-mediated mechanisms and potential effects on anti-tumor activity. |
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| Does Lower Serum Testosterone Predict Metastases-Free Survival in nmCRPC Patients Treated with Novel Antiandrogens? a Post-Hoc Analysis of SPARTAN and ARAMIS |
| Xudong Ni, MD |
| Xudong Ni presented a post-hoc analysis of the SPARTAN and ARAMIS trials, evaluating whether lower serum testosterone levels predict metastases-free survival in nmCRPC patients treated with novel antiandrogens. The analysis found no significant association between serum testosterone levels and disease progression, indicating that maintaining lower testosterone levels does not impact metastases-free survival in these patients. |
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| Efficacy of Talazoparib and Enzalutamide in mCRPC Patients Previously Treated with Androgen Receptor Pathway Inhibitors or Docetaxel – Post Hoc Analysis from Both Cohorts in TALAPRO-2 Study |
| Neeraj Agarwal, MD, FASCO |
| Neeraj Agarwal presents a post-hoc analysis of the TALAPRO-2 study, examining the efficacy of talazoparib plus enzalutamide versus placebo plus enzalutamide in mCRPC patients previously treated with androgen receptor pathway inhibitors (ARPI) or docetaxel. The analysis showed a 37% reduction in the risk of radiological progression for the overall population and a 55% reduction in HRR-deficient patients with talazoparib plus enzalutamide. |
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| Enzalutamide with or Without Leuprolide in Patients with High-Risk Biochemically Recurrent Prostate Cancer: EMBARK Post Hoc Analysis by Age |
| Neal Shore, MD, FACS |
| Neal Shore presents a post hoc analysis from the EMBARK trial, showing that both enzalutamide plus leuprolide and enzalutamide monotherapy significantly improved metastasis-free survival in high-risk biochemically recurrent prostate cancer patients, regardless of age. Although older patients experienced more serious adverse events, the treatment benefits were consistent across age groups. |
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| Phase 1/2 Trial of Oral Masofaniten (EPI-7386) in Combination with Enzalutamide Compared to Enzalutamide Alone in Metastatic Castration-Resistant Prostate Cancer |
| Christos Kyriakopoulos, MD |
| Christos Kyriakopoulos presented Phase 1/2 trial results for oral Masofaniten combined with enzalutamide in metastatic castration-resistant prostate cancer. The combination was well-tolerated and demonstrated promising efficacy, with 88% of patients achieving a PSA decline of more than 90% and favorable results compared to historical data for enzalutamide alone. The Phase 2 trial is ongoing, aiming to further assess the combination's clinical benefits. |
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