Conferences

ANZUP Mini ASM 2021: Molecular Subtypes in MIBC – Moving Toward Better Patient Selection for Treatment

(UroToday.com) The ANZUP 2021 virtual annual scientific meeting included a presentation by Dr. Sima Porten discussing the use of molecular subtypes in muscle invasive bladder cancer (MIBC) to improve patient selection for treatment. Today’s personalized medicine can be looked at through a variety of lenses:

ANZUP Mini ASM 2021: Evolving Treatment Landscape for Metastatic Urothelial Cancer

(UroToday.com) The ANZUP 2021 annual scientific meeting included a presentation by Dr. Matthew Galsky discussing the evolving treatment landscape for metastatic urothelial cancer. Dr. Galsky started by highlighting that urothelial carcinoma is not an uncommon malignancy, accounting for 82,000 new diagnoses/year in the United States and ~429,000 new diagnoses/year worldwide. However, until recently, the FDA approvals for new therapeutics in urothelial cancer over the last 30 years has been dismal:

ANZUP Mini ASM 2021: Convergence of Machine Learning and Genomics for Precision Cancer Medicine in Genitourinary Cancers and Beyond

(UroToday.com) The ANZUP 2021 virtual annual scientific meeting included a presentation by Dr. Eli Van Allen discussing the convergence of machine learning and genomics for precision cancer medicine in genitourinary cancers and beyond. As both a medical oncologist and a clinician he utilizes computational biology to assess canceromic biology for the improvement of cancer outcomes. Dr. Van Allen notes that for the last 15-20 years, there has been expanding data at the point of care, including the cost of sequencing genomes substantially decreasing and the data points available per patient increasing. This includes: whole exomes, genomes, transcriptomes, epigenomics, histopathology and unstructured electronic health record data, as summarized in the following figure:

ANZUP Mini ASM 2021: Cross-Fire Debate: Waiting for Overall Survival Data: We May Wait

(UroToday.com) As one of the final sessions of the second day of the 2021 ANZUP Annual Scientific Meeting, the Crossfire Debate included a focus on the relative importance of waiting for overall survival data before acting upon the results of clinical trials.

ANZUP Mini ASM 2021: Cross-Fire Debate: Waiting for Overall Survival Data Is Both Unnecessary and Potentially Harmful

(UroToday.com) As one of the final sessions of the second day of the 2021 ANZUP Annual Scientific Meeting, the Crossfire Debate included a focus on the relative importance of waiting for overall survival data before acting upon the results of clinical trials.

ANZUP Mini ASM 2021: Wishful Thinking - Optimal Therapy for Systemic Therapy in Upper Tract Urothelial Carcinoma

(UroToday.com) In a session entitled Clearer Vision chaired by Dr. Bertrand Tombal at the 2021 ANZUP Annual Scientific Meeting, Dr. Alison Birtle discussed what she described as wishful thinking in genitourinary oncology, with a focus on optimal therapy for systemic therapy in upper tract urothelial carcinoma (UTUC).

ANZUP Mini ASM 2021: How MRI Became the Mainstay of Active Surveillance

(UroToday.com) In a session entitled Clearer Vision chaired by Dr. Bertrand Tombal at the 2021 ANZUP Annual Scientific Meeting, Dr. Chris Parker presented on how multiparametric magnetic resonance imaging (MRI) became the mainstay of active surveillance for prostate cancer.

ANZUP Mini ASM 2021: An Update On The ANZUP Consumer Advisory Panel (CAP)

(UroToday.com) On the second day of the 2021 ANZUP Annual Scientific Meeting, one of the key sessions focused on what is happening for ANZUP trials. Ray Allen presented an update on the Consumer Advisory Panel (CAP) group. This group is composed of individuals with personal or indirect personal experiences with cancer who contribute expertise with a diverse disease-related experience.

ANZUP Mini ASM 2021: Trials in Prostate Cancer: From Initial Diagnosis To Salvage Therapy in Localized Disease and Trials in the Metastatic Prostate Cancer Setting

(UroToday.com) On the second day of the 2021 ANZUP Annual Scientific Meeting, one of the key sessions focused on what is happening for ANZUP trials. Dr. Lisa Horvath and Dr. Jarad Martin presented on trials in prostate cancer.

ANZUP Mini ASM 2021: The Trials and Tribulations of Managing Men With Metastatic Hormone-Sensitive Prostate Cancer

(UroToday.com) In a session entitled Clearer Vision chaired by Dr. Bertrand Tombal at the 2021 ANZUP Annual Scientific Meeting, Dr. Heather Payne discussed issues relating to the care of men with metastatic hormone sensitive prostate cancer (mHSPC). 

ANZUP Mini ASM 2021: Trial Updates: Germ Cell Tumors

(UroToday.com) The ANZUP annual scientific meeting’s clinical trials session included an update in germ cell tumors provided by Dr. Ben Tran. Specifically, this included an update on 5 ongoing trials/projects that ANZUP is involved with. The first trial discussed by Dr. Tran was the P3BEP trial, a randomized phase 3 trial of accelerated versus standard BEP chemotherapy for intermediate and poor risk metastatic germ cell tumors. Male and female participants 11-45 years of age with intermediate or poor-risk metastatic germ cell tumor are randomized to Arm A (standard BEP 4 x 21 day cycles) versus Arm B (accelerated BEP 4 x 14 day cycles). End of chemotherapy treatment and safety assessment is performed at 30-42 days after the last study dose, followed by surgical resection of any residual disease +/- further chemotherapy. The final response assessment occurs at 6 months from randomization or after all post-chemotherapy surgery and other interventions are complete. The trial schema for P3BEP is as follows:

ANZUP Mini ASM 2021: Trial Updates: Bladder and Penile Cancer

(UroToday.com) The ANZUP annual scientific meeting’s clinical trials session included an update in bladder and penile cancer provided by Dr. Dickon Hayne. Dr. Hayne notes that bladder cancer survival is poor in Australia (and has been getting worse over time) with a 5-year survival rate of 69% for males and 66% for females between 1982-1987, compared to 60% for males and 50% for females from 2006 to 2010. With regards to penile cancer, there is little centralization of penile cancer services or quaternary multi-disciplinary teams, no major clinical trials in Australia, little meaningful data, and worse outcomes for rural and indigenous men.

ANZUP Mini ASM 2021: Trial Updates: Renal Cell Carcinoma

(UroToday.com) The ANZUP annual scientific meeting’s clinical trials session included an update in renal cell carcinoma (RCC) provided by Dr. David Pook and Dr. Craig Gedye. Dr. Pook started by highlighting that non-clear cell RCC account for ~25% of RCC cases with less clear treatment guidelines compared to clear cell RCC. The UNISON trial is evaluating nivolumab followed by ipilimumab + nivolumab in advanced non-clear cell RCC (ANZUP 1602). The hypothesis of this trial is that patients are treated with nivolumab monotherapy upfront and that those who are nivolumab refractory may benefit from nivolumab + ipilimumab combination therapy.

APCCC 2021: What Can Meta-Analyses, Network Meta-Analyses and Subgroup Analyses Tell Us About Treatment Options: Pearls and Pitfalls

(UroToday.com) The first session of the Advanced Prostate Cancer Consensus Conference 2021 which was hosted virtually in the context of the COVID-19 pandemic focused on the management of patients with newly diagnosed metastatic hormone-sensitive prostate cancer. In this context, Dr. Claire Vale discussed analytic issues including the role of meta-analysis, network meta-analysis, and subgroup analyses to inform care for patients in this disease space.

APCCC 2021: DNA Repair Defect Aberrations – What Are the Differences Between Them and What Is the Impact on Patient Management?

(UroToday.com) The Advanced Prostate Cancer Consensus Conference 2021 virtual meeting session discussing PARP inhibitors and beyond included a presentation by Dr. Johann De Bono regarding differences between DNA repair defect aberrations and the impact on patient management. Dr. De Bono started by highlighting that >20-30% of advanced prostate cancer patients have DNA repair defect mutations, including BRCA2, ATM, PALB2, CDK12, MMR genes, BRCA1 and other genes. According to Dr. De Bono, the percentage of mutations likely increases with endocrine treatment resistance. Specific to germline DNA repair defects, 8-18% of advanced prostate cancer patients have germline mutations, with interesting variations in geography such that men in New York City have more mutations compared to men in London, compared to men in Seattle. Dr. De Bono also notes that PARP inhibitors have received regulatory approval for select cases of advanced prostate cancer, including:

APCCC 2021: Contagious Enthusiasm in PSMA-Driven Therapeutics

(UroToday.com) The Advanced Prostate Cancer Consensus Conference 2021 virtual meeting session discussing PSMA in diagnostics and therapy included a presentation by Dr. Eleni Efstathiou discussing the contagious enthusiasm of PSMA-driven therapeutics. Dr. Efstathiou notes that the VISION study outcomes1 have set the bar high, with 177Lu-PSMA-617 targeted radioligand therapy improving overall survival (OS), radiographic PFS, and quality of life by a significant margin in advance metastatic castration resistant prostate cancer (mCRPC):

 

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Dr. Efstathiou highlighted that there are several therapeutic index improvement strategies:

  • Development in the earlier disease setting
  • Combinatorial strategy: synergy, additive effect, overcoming heterogeneity driven resistance
  • Alternative agents: improved efficacy and/or (or not) improved safety
  • Precision in patient selection and treatment allocation

 

 Currently, there are efforts to treat with radioligand therapy earlier in the disease spectrum. This includes the Bullseye trial (177Lu-PSMA-I&T) and ENZA-P trial (177Lu-PSMA-617 + enzalutamide) as first-line therapy for mCRPC, the PSMAddition trial (177Lu-PSMA-617) and UpFrontPSMA trial (177Lu-PSMA-617) as first-line therapy for mHSPC, and the LuTectomy trial (177Lu-PSMA-617) as neoadjuvant therapy for localized disease:

 

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 The PRINCE phase Ib trial was initially presented at ESMO 2021, testing 177Lu-PSMA-617 targeted radioligand therapy + pembrolizumab in mCRPC men. In this trial, patients with mCRPC patients with high PSMA expression without discordant FDG avid disease on paired PSMA and FDG PET/CT scans received up to 6 cycles of Lu-PSMA-617 (6-8 GBq) every 6 weeks in conjunction with 200mg of pembrolizumab every 3 weeks for up to 2 years. With a median follow-up of 38 weeks, the PSA50 response rate was 73% (27/37 [95% CI: 56-86]):

 

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Among the 9 patients with RECIST measurable disease, 7 (78%) had a partial response. Further, rPFS and PSA-PFS at 24 weeks were 64% (95% CI: 45-79) and 68% (95% CI: 50-81), respectively:

 

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 Alternative radiopharmaceuticals to the beta emitting 177Lu-PSMA-617 targeted radioligand therapy include utilization of alpha particles. The rationale for utilization of alpha particles is a higher linear energy transfer, with a shorter range of effect; indeed, there is great anticipation of improved efficacy and safety with this class of therapeutics. Clinical reports are still limited/preliminary and mainly include 225Act-PSMA-617, which has shown potential activity in patients resistant to 177Lu-PSMA-617 targeted radioligand therapy [2] and in patients with CNS disease. Ongoing trials using alpha emitters include (i) a phase 1b trial assessing Actinium-225-J591 antibody (NCT03276572), and (ii) a phase 1b trial assessing Thorium-227-PSMA-TTC antibody (NCT03724747). PSMA-targeted bispecific T-cell engager (BiTE) immunotherapy has also been tested in the phase 1 setting:

 

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Among patients receiving acapatamab, the PSA50 rate was 50%, with a 91% grade 1/2 adverse event rate for cytokine releasing syndrome [3]. PSMA-targeted CAR-T development is in the embryonal stage limited by population vulnerability, with 5 trials ongoing (2 in the USA, 2 in China, and 1 in Germany).

 

Dr. Efstathiou concluded her presentation by emphasizing that with regards to precision in patient selection and treatment allocation, it is important to make the most of all available resources.


Presented by: Eleni Efstathiou, MD, Department of Genitourinary Medical Oncology, Houston Methodist, Houston, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 Advanced Prostate Cancer Consensus Conference, Saturday, October 9, 2021.

References:

  1. Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
  2. Feuerecker B, Tauber R, Knorr K, et al. Activity and adverse events of Actinium-225-PSMA-617 in advanced metastatic castration-resistant prostate cancer after failure of Lutetium-177-PSMA. Eur Urol 2021 Mar;79(3):343-350.
  3. Einsele H, Borghaei H, Orlowski RZ, et al. The BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer 2020;126(14):3192-3201.

 

 

APCCC 2021: Who Needs Germline Testing – Prostate Cancer

(UroToday.com) The Advanced Prostate Cancer Consensus Conference 2021 virtual meeting session discussing PARP inhibitors and beyond included a presentation by Dr. Dana Rathkopf regarding who needs germline testing and what should be tested. There are several groups of patients that need germline testing, according to Dr. Rathkopf:

APCCC 2021: Who Needs Germline Testing for Prostate Cancer and What Should Be Tested?

(UroToday.com) In this session, Dr. Dana Rathkopf discusses germline testing recommendations for men with prostate cancer. Guidelines agree that all men with metastatic prostate cancer should undergo germline testing and recommendations are evolving across the rest of the disease spectrum. New in 2021, the NCCN guidelines recommended germline testing for men with high and very high risk localized prostate cancer and to consider testing for men with intermediate risk and intraductal/cribriform carcinoma.

APCCC 2021: Tumor Molecular Testing – Tissue vs Liquid Biopsy

(UroToday.com) The third and final session of the Advanced Prostate Cancer Consensus Conference 2021 which was hosted virtually in the context of the COVID-19 pandemic focused on molecular characterization of both tissue and blood, with a focus on implications for treatment with PARP inhibitors and beyond. In this context, Dr. Andrew Armstrong discussed considerations regarding tumor molecular testing with a focus on implications for tissue-based testing as compared to liquid biopsy.

APCCC 2021: Novel and Not So Novel Agents and Where To Place Them in the Treatment Sequence for Prostate Cancer

(UroToday.com) The third and final session of the Advanced Prostate Cancer Consensus Conference 2021 which was hosted virtually in the context of the COVID-19 pandemic focused on molecular characterization of both tissue and blood, with a focus on implications for treatment with PARP inhibitors and beyond. In the final talk of this session, Dr. Eric Small discussed the role of both novel and proven treatment options in advanced prostate cancer and how we may best utilize these in treatment sequencing.

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