The ASCO GU symposium was held in San Francisco from February 16-18, 2023. This is a large multidisciplinary conference that brings together GU oncology investigators from all over the world to present new data and educate. As a clinical and translational investigator, the tremendous opportunities to network with colleagues and potential collaborators from academia and industry are energizing at ASCO GU. Here, I summarize the key data presented at ASCO GU 2023.
While there was no immediately practice-changing data, one phase III study, TALAPRO-2, evaluated talazoparib (PARP inhibitor) and may fit into that category with implications in the near future. In this context, a couple of PARP inhibitors are already approved by the US FDA for metastatic castration-resistant prostate cancer (mCRPC): Olaparib has full approval based on the phase III PROFOUND trial (germline or somatic homologous recombination repair [HRR] gene-mutated mCRPC who have progressed following enzalutamide or abiraterone) and rucaparib has accelerated approval based on the phase II TRITON-2 trial (deleterious germline and/or somatic BRCA-associated mCRPC progressing following androgen receptor-directed therapy and a taxane). The TRITON Phase III trial was reported at ASCO GU '23 and corroborates the benefit from rucaparib monotherapy by demonstrated improved rPFS over control therapy in mCRPC with BRCA1, BRCA2 or ATM alteration and progression after a novel hormonal antagonist (NHA). These data may lead to full approval of rucaparib by the US FDA. The natural next step for the investigation of PARP inhibitors is the role of combination therapy in the clinic. Indeed, at ASCO GU '23, the TALAPRO-2 phase III trial was presented and demonstrated a significant improvement (HR 0.63, p<0.001) in radiographic progression-free survival (rPFS) and quality of life with manageable toxicities for the combination of talazoparib plus enzalutamide vs. placebo plus enzalutamide as first-line therapy for mCRPC regardless of homologous recombination repair (HRR) defects. These data arrive on the heels of the recent demonstration of improved rPFS for the combination of olaparib and abiraterone + prednisone in unselected as well as the HRR population in the PROpel phase III trial, which led to regulatory approval in Europe in December 2022. In contrast, the MAGNITUDE trial previously demonstrated improved rPFS in a selected population of first-line mCRPC patients with HRR alterations, when combining niraparib with abiraterone acetate + prednisone. The decision of the US FDA regarding the combination of abiraterone with a PARP inhibitor remains to be seen. Moreover, ongoing phase III trials are evaluating PARP inhibitors in earlier hormone-sensitive disease and earlier phase trials are evaluating other novel combinations incorporating PARP inhibitors.
In the realm of other GU malignancies, there were mostly practice-reaffirming and practice-informing presentations. One presentation is likely to be practice changing in the realm of imaging for renal cell carcinoma (RCC): the ZIRCON phase III study evaluated 89Zr-DFO-girentuximab, an investigational renal cell carcinoma (RCC) positron emission tomography (PET) imaging agent that binds to CAIX and demonstrated excellent accuracy (86%) in identifying clear cell RCC safely and non-invasively. Thus, we may finally have a PET imaging modality in the clinic to stage and monitor clear cell RCC. Future therapeutic applications of this backbone are also being pursued. The update from CHECKMATE274 continues to show robust disease-free survival advantage and no new safety signals with adjuvant nivolumab for high-risk muscle-invasive urothelial carcinoma especially the PD-L1 high tumor subgroup, although survival was not presented. The combination of platinum-based chemotherapy and atezolizumab has not provided clear or meaningful benefits from the IMvigor130 phase III trial as updated at ASCO-GU-23. This trial did not demonstrate significant improvement in survival, although there was an intriguing signal for potentially better efficacy with the cisplatin (vs. carboplatin) backbone. The CHECKMATE901 trial has a dedicated large randomized sub-study comparing cisplatin-gemcitabine with or without nivolumab in combination, and the results are awaited with great interest. A real-world retrospective study by the Global Society of Rare GU Tumors (GSRGT) evaluated the activity of immune checkpoint inhibitors in advanced penile carcinoma and identified an objective response rate of 8.5% with PD1/L1 inhibitor monotherapy. Given the enormous challenges in conducting and accruing patients to trials of this orphan malignancy, a paradigm of real-world retrospective studies conducted in committed institutions to generate high quality real-world data toward regulatory approvals for penile carcinoma patients should be considered.
In order to make larger gains in clinical outcomes, a better understanding of tumor biology is imperative. Additionally, a better future also depends on the vigorous development of precision medicine, which is critical to advance cost-effective therapy, which may lead to downstream benefits from sustainable and equitable healthcare delivery.
Dr. Sonpavde is on the advisory board of EMD Serono, BMS, Merck, Seattle Genetics/Astellas, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Lucence Health, IMV, and Vial. He is a consultant/Scientific Advisory Board for Suba Therapeutics and Syapse. He has research support to institution from Sanofi, Astrazeneca, Gilead, Helsinn, Lucence, EMD Serono, Jazz Therapeutics, and Genecentric. He is a speaker for BIO – INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, Seagen, Gilead, Natera, and Exelixis. He is on the Data safety monitoring committee for Mereo. His spouse is employed by Myriad, and he receives Writing/Editor fees from Uptodate and Elsevier Practice Update Bladder Cancer Center of Excellence.
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