ESMO 2022

(UroToday.com) The 2022 ESMO annual meeting included a session focusing on PSMA biology, diagnostics and treatment and a presentation by Dr. Shahneen Sandhu discussing ¹⁷⁷-Lutetium (Lu)-PSMA for prostate cancer treatment. Dr. Sandhu noes that the definition of PSMA theranostics is “targeted therapeutic and diagnostic companion,” specifically a ⁶⁸Ga-PSMA-11 PET/CT + Lu-PSMA therapy. The first major trial utilizing Lu-PSMA in prostate cancer was the TheraP trial.¹ This open label, phase II trial evaluated Lu-PSMA vs cabazitaxel for men with mCRPC after docetaxel. To screen into the study, all men had both ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT and were required to have high PSMA-expression (at least one site with SUV_max ≥ 20) and no sites of FDG-positive/PSMA-negative disease. All patients had progressive disease with rising PSA ≥20 ng/mL after docetaxel and 91% had received prior enzalutamide or abiraterone. Overall, 200 patients were randomized 1:1 to Lu-PSMA 6-8 GBq every 6 weeks for up to 6 cycles of therapy or cabazitaxel 20 mg/m² every 3 weeks for up to 10 cycles. Patients were stratified based on disease burden and prior anti-androgen therapy:

(UroToday.com) The 2022 ESMO annual meeting included a session focusing on multi-disciplinary updates in biomarkers in urinary cancers and a presentation by Dr. Elisabeth de Vries discussing the latest imaging advances in PET and beyond translated to bladder and kidney cancers. Dr. de Vries notes that molecular imaging takes advantage of tumor biology in vivo and numerous targets for ligands. With regards to PET imaging and translation to bladder and kidney cancers, the potential aim is to predict who will respond to what treatment and PET imaging. For bladder cancer, this includes HER2 (an antibody drug conjugate), immune checkpoint inhibitors, and immune response with CD8 imaging. For kidney cancer, this includes angiogenesis inhibitors, immune checkpoint inhibitors, and immune response with CD8 imaging.

(UroToday.com) The 2022 ESMO annual meeting included a session focusing on PSMA biology, diagnostics, and treatment and a presentation by Dr. Karim Fizazi discussing PSMA Targeted T cell engagers. Dr. Fizazi started by noting that existing immunotherapies have minimally impacted outcomes of men with mCRPC, even though CTLA-4 inhibition was associated with excess in long-term survivors in a phase 3 trial. T cell engagers are “two-hands molecules” that engage cancer cells (identified by a target protein) and T cells, leading to (i) cancer cell lysis (independent of T cell receptor specificity), (ii) peptide presentation by the MHC system, and (iii) T cell co-stimulation signals. The following clinical efficacy data with PSMA-targeted T cell engagers is available:

(UroToday.com) The 2022 ESMO annual meeting included a session focusing on multi-disciplinary updates in biomarkers in urinary cancers and a presentation by Dr. Lisa Derosa discussing the importance of the microbiome. Dr. Derosa notes that we have identified a number of factors that impact tumor growth and response to cancer treatment, which now include polymorphic microbiomes. However, although the impact of the gut microbiome in genitourinary cancer immunotherapy was first studied, it was done serendipitously.

(UroToday.com) On Monday, September 12, 2022, in Presidential Symposium III at the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Chouieri presented highly awaited results from the COSMIC-313 trial, examining the role of triplet therapy with cabozantinib, nivolumab, and ipilimumab as first-line treatment in patients with advanced renal cell carcinoma (aRCC).

(UroToday.com) On Monday, September 12, 2022, in Presidential Symposium III at the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Parker presented results of the RADICALS-HD trial examining the effect of differing durations of androgen deprivation therapy (ADT) among men receiving post-operative radiotherapy following radical prostatectomy for prostate cancer. This is a key question as, though there is substantial high-quality evidence regarding the role and durations of ADT for men receiving primary radiotherapy for the treatment of prostate cancer, there is considerable uncertainty regarding its role and duration for men who are receiving post-prostatectomy radiotherapy.

(UroToday.com) Following presentations from Dr. Maxime Meylan discussing predictive biomarkers in advanced renal cell carcinoma (RCC) based on ancillary analyses of the BIONIKK trial, Dr. Carolina Alves Costa Silva examining changes in gut microbiota during standard systemic therapy for metastatic RCC, and Dr. Ramaprasad Srinivasan providing updated longer-term follow-up of the LITESPARK-004 trial assessing the HIF-2alpha inhibitor belzutifan in von-Hippel-Lindau disease associated neoplasms, Dr. Guillermo De Velasco Oria provided an invited discussion to contextualize these results in the second Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers.

(UroToday.com) During the second Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers, Dr. Alves Costa Silva presented a longitudinal assessment of gut microbiota during treatment for metastatic renal cell carcinoma (mRCC). It has previously been noted that the baseline gut microbiota composition is associated with outcomes for patients receiving immune-checkpoint blockade for mRCC.

(UroToday.com) Following presentations from Dr. Nizar Tannir discussing results of the PIVOT-09 trial examining bempegaldesleukin plus nivolumab compared to the investigator’s choice of Sunitinib or Cabozantinib in first-line treatment of advanced renal cell carcinoma (RCC) and from Dr. Jonathan Rosenberg discussing the role of enfortumab vedotin either as monotherapy or in combination with pembrolizumab in cisplatin-ineligible patients with advanced urothelial cancer (UC), Dr. Laurence Albiges provided an invited discussion to contextualize these results in the Proffered Paper Session 2 of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers.

(UroToday.com) During the second Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers, Dr. Andrea Necchi presented results from the CheckMate 274 trial assessing tumor and immune features predictive of disease-free survival. CheckMate 274 randomized patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection to receive adjuvant nivolumab or placebo, demonstrating improved disease-free survival (DFS) with adjuvant nivolumab in the intent-to-treat (ITT) and tumor PD-L1 expression ≥ 1% populations.