The Vanderbilt University

Dr. Eugene Pietzak discusses the challenges of evaluating comparative effectiveness of FDA-approved treatments for BCG-unresponsive bladder cancer, emphasizing the need for stage-specific clinical trials, better biomarkers, and objective measures for minimal residual disease to guide treatment selection and improve patient care.

Muhamed Baljevic, MD, FACP, will present long-term follow-up results of the phase 3 AQUILA study evaluating daratumumab monotherapy vs active monitoring in high-risk smoldering multiple myeloma at the 2024 ASH Annual Meeting. Jorge Cortes, MD, will update the 96-week data from the phase 3 ASC4FIRST trial on asciminib in newly diagnosed chronic myeloid leukemia, highlighting efficacy and safety compared to TKIs.

Sunil Patel and Max Kates present a phase II trial of sequential gemcitabine and docetaxel therapy in BCG-naive non-muscle-invasive bladder cancer patients, achieving 100% complete response at three months and 92% at twelve months. The therapy involves weekly induction followed by monthly maintenance, addressing BCG shortages and offering an alternative to cystectomy. Challenges include coordination with pharmacy and nursing teams, chair time, and treatment protocols, but the combination's effectiveness is attributed to different mechanisms of action and potential immunotherapeutic effects.

Ursula Vogl discusses key prostate cancer trials from ESMO 2024: PATCH (transdermal estradiol vs. LHRH analogs in non-metastatic), ARANOTE (darolutamide in metastatic hormone-sensitive), and PEACE-3 (radium-223 plus enzalutamide in metastatic castration-resistant). Also covered are STAMPEDE (metformin's metabolic benefits) and SPLASH (lutetium PSMA-I&T therapy). Practical considerations include metformin's potential role despite lacking overall survival benefit and challenges in implementing radioligand therapy due to logistical, regulatory, and reimbursement issues.

Alan Tan, MD discusses the complexities of choosing immuno-oncology (IO)–based treatment regimens for renal cell carcinoma (RCC), highlighting the 8-year follow-up data from the CheckMate 214 trial showing nivolumab plus ipilimumab's median overall survival of 52.7 months vs 37.8 months with sunitinib. He notes the FDA approval of pembrolizumab plus lenvatinib based on the CLEAR trial, and the ongoing questions regarding the use of IO-TKI regimens. Tan emphasizes the need for future research to combat resistance to immune checkpoint inhibition and the importance of symptom burden in treatment decisions.

Interim phase 1 trial results for allogeneic CAR T therapy P-BCMA-ALL01 show 91% response rate in 23 multiple myeloma patients, with no dose-limiting toxicities or graft-versus-host disease.

Ignacio Durán discusses ESMO 2024 highlights in non-prostate genitourinary oncology, focusing on kidney and bladder cancer. Key findings include challenging the sequencing of checkpoint inhibitors in kidney cancer and new treatment options for non-clear cell carcinoma. In bladder cancer, studies like SunRISe-4, TOMBOLA, and NIAGARA could impact clinical practice, exploring alternatives to cisplatin-based neoadjuvant chemotherapy, ctDNA for patient selection in adjuvant therapy, and perioperative immunotherapy, respectively. Further research is needed to refine patient selection and optimize treatment strategies.

The Kleberg Foundation awarded $1 million to Vanderbilt for immunotherapy research on colorectal cancer, targeting DDR1, TGFBi, and DPEP1 proteins to benefit microsatellite stable cases. The grant supports uncovering supermere mechanisms, identifying immune exclusion biomarkers, and evaluating targeted immunotherapy efficacy.

Cathy Eng discusses unmet needs in metastatic colorectal cancer (mCRC) treatment, focusing on BRAF V600E–mutant tumors, KRAS mutations, and refractory patients without actionable mutations. Despite FDA approvals for some combinations, effective options post-progression are lacking, emphasizing the need for ongoing clinical trials.