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HIGHLIGHTS FROM THE 2024 EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY ANNUAL MEETING
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| Proffered Paper Session: GU Tumours, Prostate |
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| Decipher mRNA Score for Prediction of Survival Benefit from Docetaxel at Start of Androgen Deprivation Therapy for Advanced Prostate Cancer: An Ancillary Study of the STAMPEDE Docetaxel Trials
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| Emily Grist, MBBS, PhD
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| In this proffered paper session, Dr. Emily Grist presented the results of an ancillary study of the STAMPEDE Docetaxel trial evaluating the genomic classifier Decipher® mRNA score for predicting a survival benefit with docetaxel doublet therapy intensification for metastatic hormone sensitive prostate cancer (mHSPC) patients.
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| Cabozantinib plus Atezolizumab versus 2nd Novel Hormonal Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: Final Overall Survival Results of the Phase III, Randomized, CONTACT-02 Study
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| Neeraj Agarwal, MD
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| Dr. Neeraj Agarwal presented the final overall survival results of CONTACT-02, a phase III randomized trial of cabozantinib plus atezolizumab versus a 2nd novel hormonal therapy (NHT) in patients with metastatic castrate-resistant prostate cancer (mCRPC).
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| Invited Discussant: CONTACT-02 Study and STAMPEDE Docetaxel Trials
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| Rana McKay, MD
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| Dr. Rana McKay delivered the discussant session for CONTACT-02 and the post-hoc analysis of STAMPEDE Docetaxel assessing Decipher® as a potential predictive biomarker for overall survival in metastatic hormone sensitive prostate cancer (mHSPC) patients receiving docetaxel doublet therapy.
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| Mini Oral Session: GU Tumours, Prostate |
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| Prostate Cancer Efficacy Results from a Randomized Phase 3 Evaluation of Transdermal Estradiol Versus LHRH Agonists for Androgen Suppression in M0 Prostate Cancer |
| Ruth E. Langley, PhD |
| Ruth Langley presented results from a phase 3 trial comparing transdermal estradiol to LHRH agonists for androgen suppression in M0 prostate cancer. Transdermal estradiol was shown to be as effective as LHRH agonists, with similar metastasis-free survival (86% vs. 87%) and overall survival. Additionally, transdermal estradiol improved bone mineral density, reduced cardiovascular toxicity, and enhanced quality of life, making it a viable standard-of-care option for androgen deprivation therapy (ADT) in M0 prostate cancer. |
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| Efficacy and Safety of Darolutamide plus ADT in Patients with mHSPC from the Phase 3 ARANOTE Trial |
| Fred Saad, MD, FRCSC |
| Fred Saad presented at ESMO 2024 on the ARANOTE trial, showing that darolutamide plus ADT significantly improved radiological progression-free survival compared to ADT alone in patients with mHSPC. Darolutamide also demonstrated benefits across secondary endpoints, including time to castration-resistant prostate cancer and PSA progression, with a favorable safety profile and fewer treatment discontinuations. |
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| Invited Discussant: Phase 3 ARANOTE Trial, Phase 3 Evaluation of Transdermal Estradiol Versus LHRH Agonists and Ancillary Study of the PEACE-1
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| Niven Mehra, MD
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| Niven Mehra discusses three prostate cancer trials. The ARANOTE phase 3 trial showed that darolutamide plus ADT significantly improved rPFS for mHSPC patients. The phase 3 evaluation of transdermal estradiol versus LHRH agonists. Lastly, the PEACE-1 ancillary biomarker study which identified five phenotype subgroups but found no significant predictive biomarkers for abiraterone treatment.
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| Adding Metformin to ADT for Patients with mHSPC: Overall Survival Results from the Multi-Arm, Multi-Stage Randomized Platform Trial STAMPEDE
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| Silke Gillessen Sommer, MD
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| Silke Gillessen presented results from the STAMPEDE trial, assessing whether adding metformin to androgen deprivation therapy improves overall survival in patients with metastatic hormone-sensitive prostate cancer. The trial found no significant overall survival benefit for metformin in unselected patients, although there was some evidence of benefit in high-volume disease.
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| RAPSON: Open-Label, Multicenter Randomized Trial of Radium-223 -> Docetaxel Versus Docetaxel -> Radium-223 Sequence in mCRPC with Prospective Biomarker Evaluation
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| Vincenza Conteduca, MD
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| Vincenza Conteduca presented the results of the RAPSON trial, which evaluated the sequencing of Radium-223 followed by docetaxel versus docetaxel followed by Radium-223 in patients with bone-dominant metastatic castration-resistant prostate cancer. The trial aimed to determine the optimal sequence of these treatments to improve health-related quality of life and tolerability.
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| Invited Discussant: RAPSON: Open-Label, Multicenter Randomized Trial of Radium-223 and Adding Metformin to ADT for Patients with mHSPC
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| Deborah Mukherji, MBBS, FRCP
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| Deborah Mukherji discussed two key trials in prostate cancer treatment. The RAPSON trial demonstrated that sequencing Radium-223 before docetaxel improves quality of life in bone-dominant mCRPC patients, although no significant difference in progression-free or overall survival was found between the two treatment arms.
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| CC-94676-PCA-001: Clinical Activity of BMS-986365, a Dual Androgen Receptor Ligand-Directed Degrader and Antagonist, in Heavily Pretreated Patients with mCRPC |
| Dana Rathkopf, MD |
| Dana Rathkopf presented data from a study of BMS-986365, a dual androgen receptor degrader and antagonist, in heavily pretreated mCRPC patients. The drug was well-tolerated, with QTc prolongation as the most common adverse event, manageable by dose reduction. BMS-986365 showed promising anti-tumor activity, with dose-dependent PSA reductions and longer radiographic progression-free survival in chemotherapy-naïve patients. |
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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 |
| Niven Mehra presented results from the phase II INSPIRE trial, evaluating nivolumab 3mg/kg and ipilimumab 1mg/kg in molecularly selected mCRPC patients. The trial met its primary endpoint, with a disease control rate >6 months of 38%, with the highest efficacy observed in mismatch repair-deficient patients, who had an 81% disease control rate, 75% objective response rate, and a median progression-free survival of 32.7 months. |
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| What’s on the Horizon for Metastatic Prostate Cancer Patients? |
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| Targeting Epigenetic Pathways
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| Wilbert Zwart, MD
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| Wilbert Zwart’s presentation explores the role of epigenetic pathways in metastatic prostate cancer, focusing on how modifications like H3K27ac influence gene expression and treatment resistance. Key findings included the reprogramming of FOXA1 and the identification of ARNTL as a novel therapeutic target, with ongoing research into epigenetic biomarkers and drug combinations like enzalutamide and vorinostat.
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| Hematologic Impact of [177Lu]Lu-PSMA-617 Versus ARPI Change in Patients with Metastatic Castration-Resistant Prostate Cancer in PSMAfore
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| Kim N. Chi, MD
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| Kim Chi presents data from the PSMAfore trial, which compared the hematologic safety of [177Lu]Lu-PSMA-617 to androgen receptor pathway inhibitor (ARPI) changes in taxane-naive mCRPC patients. The trial revealed a higher incidence of hematologic treatment-emergent adverse events in patients receiving 177Lu-PSMA-617 compared to ARPI changes.
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| A New Prognostic Model of Overall Survival in Patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC) |
| Susan Halabi, PhD |
| Susan Halabi presented a new prognostic model for overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The model, developed using data from four phase III trials, identified key prognostic factors, including disease volume, ECOG performance status, age, opioid use, and laboratory values like PSA and hemoglobin. |
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| Clinical Prognostic Factors Within the High-Volume Subgroup of Metastatic Hormone Sensitive Prostate Cancer in ENZAMET (ANZUP 1304) |
| Anis Hamid, MBBS |
| Anis Hamid presents a post-hoc analysis from the ENZAMET trial, identifying clinical prognostic factors in high-volume metastatic hormone-sensitive prostate cancer. High bone burden (elevated alkaline phosphatase) and high Gleason scores were linked to shorter overall survival and prostate cancer-specific survival in patients with high-volume disease, particularly in those with synchronous metastases. |
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| TAMARACK: Randomized Phase 2 Trial of the B7-H3 Targeting Antibody Drug Conjugate Vobramitamab |
| Johann De Bono, MD, MSc, PhD, FRCP |
| Johann De Bono presents the TAMARACK study, a Phase 2 trial evaluating the B7-H3 targeting antibody-drug conjugate vobramitamab in mCRPC. The study tested two dosing regimens and found that while both doses showed similar efficacy in rPFS and PSA response rates, the higher dose was associated with a higher overall response rate. |
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| The STAMPEDE2 Niraparib-Abiraterone Acetate + Prednisolone Trial: A Phase III, Randomized, Open-Label Trial in Patients with Metastatic Prostate Cancer with a Deleterious Alteration in a HRR Gene Starting ADT
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| Sarah Howlett, MBBS
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| Sarah Howlett presents the STAMPEDE2 trial, a phase 3, randomized, open-label study evaluating niraparib with abiraterone acetate and prednisolone in patients with metastatic hormone-sensitive prostate cancer who have deleterious alterations in HRR genes. The trial aims to assess whether this combination, starting alongside ADT, improves survival compared to standard-of-care treatments.
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| The STAMPEDE2 Stereotactic Ablative Body Radiotherapy Trial: A Phase III, Randomized, Open-Label Trial in Patients with Newly Diagnosed Oligometastatic Prostate Cancer Starting ADT
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| Hoda Abdel-Aty, MD
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| Hoda Abdel-Aty presented the STAMPEDE2 SABR trial, a phase 3, randomized, open-label study evaluating the addition of stereotactic ablative body radiotherapy (SABR) to standard of care for newly diagnosed synchronous oligometastatic prostate cancer. The trial will assess whether SABR improves rPFS and overall survival compared to standard treatments, which include long-term ADT, androgen receptor signaling inhibitors, and possibly docetaxel.
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| The STAMPEDE2 (177Lu-PSMA-617) Trial: A Phase III, Randomised, Open-Label Trial in Patients with Metastatic Prostate Cancer Starting ADT
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| Minal Padden-Modi, MD
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| Minal Padden-Modi presents the STAMPEDE2 trial, a phase 3, randomized, open-label study investigating the use of 177Lu-PSMA-617 in combination with standard care for newly diagnosed metastatic prostate cancer starting ADT. The trial evaluates an accelerated dosing schedule of 177Lu-PSMA-617, given its potential to enhance the efficacy of hormone therapy by targeting upregulated PSMA expression.
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| HARMONY: A Phase II Study of Niraparib/Abiraterone Acetate plus Prednisone for Hispanic/Latino and Non-Hispanic Black Patients with Metastatic Hormone Sensitive Prostate Cancer and Deleterious Homologous Recombination Repair Alterations
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| Qian Qin MD
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| Qian Qin presented the HARMONY trial, a phase II study evaluating the combination of niraparib, abiraterone acetate, and prednisone in Hispanic/Latino and non-Hispanic Black patients with metastatic hormone-sensitive prostate cancer and deleterious HRR alterations. Dr. Qin highlighted the trial's potential to enhance treatment strategies and outcomes for Hispanic/Latino and non-Hispanic Black patients with mHSPC.
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| Determination of Tumor PSMA Expression in Prostate Cancer from Blood Using a Novel Epigenomic Liquid Biopsy Platform |
| Praful Ravi, MB, BChir, MRCP |
| Praful Ravi presents a novel epigenomic liquid biopsy platform at ESMO 2024 that accurately determines tumor PSMA expression in mCRPC from blood samples. The study demonstrated that epigenomic profiling of plasma can serve as a minimally invasive method to predict PSMA PET scan results, potentially enhancing patient selection and treatment strategies for PSMA-targeted therapies. |
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| Radioligand Theranostics in Prostate Cancer: Status Quo and New Developments
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| Ken Herrmann, MD
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| Ken Herrmann's presentation reviewed advancements in radioligand theranostics for prostate cancer, emphasizing the progress of 177Lu-PSMA-617 in clinical trials such as VISION and TheraP, which show improved overall and radiographic progression-free survival compared to standard treatments and cabazitaxel. New developments include early-line therapies, novel radioligand versions, combination approaches, and emerging targets and radionuclides, marking significant steps toward integrating radioligand therapy into routine prostate cancer management.
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| Tumor Suppressor Gene Signature Predicts Early Progression in mHSPC Patients |
| Marta Garcia De Herreros, MD |
| Marta Garcia De Herreros presents on a tumor suppressor gene signature predicting early progression in mHSPC patients treated with androgen receptor signaling inhibitors. The study found that low expression of tumor suppressor genes was associated with shorter CRPC-free survival and a higher incidence of aggressive cancer variants, suggesting that this gene signature could be a useful predictor for early progression and guide the development of targeted therapies.4o mini |
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