Previewing ESMO 2023: The Latest Genitourinary Research, Trials Due to Be Presented

The European Society for Medical Oncology (ESMO) Congress will be held October 20-24 in Madrid, Spain, this year.¹ ESMO is one of the primary professional organizations for the development and advancement of medical oncology and the society of reference for oncology education. Every year, the ESMO Congress includes a session on the latest research and developments in medical oncology. The event also highlights abstracts and research articles related to genitourinary malignancies, which are presented by some of the foremost medical oncologists. Conference attendees often have the chance to interact with the presenters and panel members, and those attending virtually can follow along in real time or review the recorded content on their own.

In this article, I have highlighted some of the most exciting abstracts and presentations—which may lead to practice-changing consequences for clinicians and patients worldwide—due to be shared during ESMO 2023.

In the realm of prostate cancer, patients who are at higher risk of biochemical failure following radical prostatectomy are often referred to radiation oncology for further treatment. Results of the RADICALS-RT trial (NCT00541047)² will be presented by Dr. Noel Clarke. In this trial, the authors sought to assess the optimal timing of radiation after surgery, as well as the use of adjunctive androgen deprivation therapy (ADT). The original trial rationale cited that the combination of radiation therapy and ADT may enhance the tumor kill rate of prostate cancer cells. The trial’s initial results, which were published in 2019, demonstrated “increased risk of urinary morbidity” with adjuvant radiation therapy and no benefit for adjuvant radiation in the patient group enrolled.³

Another area of interest in prostate cancer is prostate-specific membrane antigen (PSMA)-directed radioligand therapy, which has shown substantial benefit as a therapeutic option in patients with metastatic castration-resistant prostate cancer (mCRPC). PSMA is overexpressed in patients with prostate cancer and can be up to 1000 times higher in those patients than in benign prostatic tissue.⁴ Expression of the PSMA peptide to the extracellular surface of the cell facilitates binding of PSMA-directed agents, whether it be for diagnostic or therapeutic purposes. The landmark VISION trial originally presented in 2021 demonstrated a prolonged overall survival benefit and an extended radiographic progression-free survival (PFS) benefit in patients with mCRPC refractory to first- and second-line therapies who received 6 cycles of ¹⁷⁷Lu-PSMA-617 (Pluvicto).⁵

Continuing this trend of innovating the use of radiopharmaceuticals such as ¹⁷⁷Lu-PSMA-617, the results of the phase 2 ANZUP 1901 trial⁶ will be presented by Dr. Louise Emmett. In this trial, the authors sought to evaluate the utility of ¹⁷⁷Lu-PSMA-617 in conjunction with enzalutamide versus enzalutamide alone in patients with mCRPC at high risk for disease progression. The trial’s primary end points, which will be familiar to most clinicians, include prostate-specific antigen and PFS. Enzalutamide data have been available for nearly 10 years now (since the publication of the phase 3 AFFIRM trial results,⁷ which demonstrated benefit in the postchemotherapy mCRPC space), and the potential synergistic therapeutic effect of combining a newer technology like ¹⁷⁷Lu-PSMA-617 with enzalutamide has theoretical promise. I am excited to see the ANZUP 1901 results.

ESMO 2023 will also offer exciting content on the latest in bladder cancer. Dr. James Catto will be presenting the results of the THOR-2 (NCT04172675) Cohort 1 arm. In brief, THOR-2 sought to elucidate the effect of erdafitinib, an orally bioavailable FGFR1-4 inhibitor, in patients with high-risk, bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (nMIBC) with FGFR mutations.⁸ This multicohort trial consists of 3 arms: Cohort 1 is comprised of patients with papillary-only disease, Cohort 2 of patients with carcinoma in-situ with or without papillary disease, and Cohort 3 of patients with intermediate-risk nMIBC.⁸ The results presented at ESMO will focus on Cohort 1. Patients in that cohort were randomized 2:1 to erdafitinib versus intravesical mitomycin or gemcitabine (decided by investigator per patient).⁸ The primary end point for Cohort 1 is recurrence-free survival. The results from this trial, if promising, may facilitate yet another oral therapeutic option for select patients with BCG-unresponsive nMIBC. At the 2023 ASCO® Annual Meeting, Dr. Catto presented an interim analysis of the entire THOR-2 study.⁹ Those results demonstrated a median duration of treatment response of 3 months, as well as a relatively favorable treatment-related adverse event profile.

In addition to the latest research, ESMO 2023 will offer several educational seminars given by experts. For information and updates related to advanced renal cell carcinoma (RCC), I recommend tuning in to Dr. Toni K. Choueiri’s presentation on Friday, October 20. He plans to review the current treatment paradigms for metastatic RCC.

Another great element of the ESMO Congress is the incorporation of question-and-answer sessions, which are often curated by discussion chairs and allow for thoughtful comments, critiques, and discussion among the clinical community.

In conclusion, this event is a highly influential oncology experience for clinicians and clinician researchers. It provides the public, including patients and health care team members of all kinds, with the latest and greatest advances and research in the medical oncology space.

Akhil Abraham Saji, MD, Fellow at the University of Southern California, is a urologist specializing in minimally invasive surgery and urologic oncology with an interest in technology-driven innovation within health care.

References

1. ESMO Congress 2023. ESMO. Accessed September 24, 2023. https://www.esmo.org/meeting-calendar/esmo-congress-2023
2. Radiation Therapy and Androgen Deprivation Therapy in Treating Patients Who Have Undergone Surgery for Prostate Cancer (RADICALS). ClinicalTrials.gov. Updated October 13, 2017. Accessed October 2, 2023. https://clinicaltrials.gov/study/NCT00541047
3. Parker C, Clarke NW, Cook A, et al. LBA49_PR – Timing of radiotherapy (RT) after radical prostatectomy (RP): first results from the RADICALS RT randomised controlled trial (RCT) [NCT00541047]. Ann Oncol. 2019;30:v883-v884. doi:10.1093/annonc/mdz394.042
4. Jones W, Griffiths K, Barata PC, Paller CJ. PSMA theranostics: review of the current status of PSMA-targeted imaging and radioligand therapy. Cancers. 2020;12(6):1367. doi:10.3390/cancers12061367
5. Sartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
6. Emmett L, Subramaniam S, Joshua AM, et al. ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). BJU Int. 2021;128(5):642-651. doi:10.1111/bju.15491
7. Sternberg CN, de Bono JS, Chi KN, et al. Improved outcomes in elderly patients with metastatic castration-resistant prostate cancer treated with the androgen receptor inhibitor enzalutamide: results from the phase III AFFIRM trial. Ann Oncol. 2014;25(2):429-434. doi:10.1093/annonc/mdt571
8. A randomized phase 2 study of erdafitinib versus investigator choice of intravesical chemotherapy in subjects who received bacillus Calmette-Guérin (BCG) and recurred with high risk non-muscle-invasive bladder cancer (NMIBC). ClinicalTrials.gov. Updated September 13, 2023. Accessed October 2, 2023. https://clinicaltrials.gov/study/NCT04172675
9. Catto JWF, Tran B, Master VA, et al. Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non–muscle-invasive bladder cancer (HR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 2 interim analysis results. JCO. 2023;41(6_suppl):503. doi:10.1200/JCO.2023.41.6_suppl.503