The Future of Treatments for Muscle Invasive Bladder Cancer

EP: 1.Case Overview: A 75-Year-Old Woman with High-Risk Muscle Invasive Bladder Cancer

EP: 2.Standard of Care for Muscle-Invasive Bladder Cancer

EP: 3.Adjuvant Nivolumab for High-Risk Muscle-Invasive Bladder Cancer

EP: 4.Ongoing Clinical Trials in Muscle-Invasive Bladder Cancer

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EP: 5.The Future of Treatments for Muscle Invasive Bladder Cancer

Karim Chamie, MD: The field is growing significantly.; they're really promising exciting new drugs on the horizon. Drugs that were being used in the 2nd and 3rd-line settings are now available for patients potentially in the neoadjuvant and the adjuvant settings. You've got the TROPHY-U-01 study, which is an anti-trope antibody drug conjugate: sacituzumab/govitecan. We have enfortumab vedotin based on the 201 and 301 studies where we use it. We have the BCL2001, which is the erdafitinib study for patients who are FGFR23-positive. There is recent data from ESMO [European Society for Medical Oncology] about a benefit in patients with lung cancer being treated with anti-PD-L1 and anti-TIGITs. All in all, the field is booming, and this is really an exciting time to be a physician who treats patients with bladder cancer.

I do expect that patients who are treated at academic centers will oftentimes see a multidisciplinary team. We have medical oncologists who are going now to become increasingly more familiar not only with chemotherapy, but the adverse effects profile and the toxicity profiles of antibody drug conjugates, immunotherapies, and targeted therapies. There's going to be increasing collaboration not just with medical oncology but, with medicine. That is because some of these drugs may have some toxicities and we need to identify those who are at increased risk. I think the radiation oncologists always are involved in patients who've undergone say a radical cystectomy and have a positive margin but are also involved in patients who are not good surgical candidates for a cystectomy and may benefit from bladder preservation. The utilization of some of these novel agents may be synergistic with radiation therapy. It’s going to be really an exciting field, and having a multidisciplinary team is key as we utilize and offer these newer drugs to these patients.

In my opinion, the biggest unmet need in bladder cancer has to do with identifying patients who really need adjuvant therapies and some of these more aggressive treatments. For instance, is it possible that some patients who have T2 disease after neoadjuvant chemotherapy may not need adjuvant nivolumab? Is it possible that a patient who gets neoadjuvant chemotherapy may not need a radical cystectomy? Those are things that we're going to end up trying to answer over the next 5-10 years. And I think it's going to - we're going to have to utilize things like circulating tumor DNA and other biomarkers to determine who needs more aggressive treatments like a cystectomy after neoadjuvant chemotherapy or adjuvant therapies after radical cystectomy. Those are the unmet needs, and those are the questions that we need answered.

The key takeaway from this talk is that these drugs are becoming increasingly more tolerated. Their adverse events profiles are not as significant as we've had with historic drugs. Since these are better tolerated, neoadjuvant chemotherapy is tolerated better; adjuvant nivolumab is better tolerated, and radiation therapy is better tolerated. As we become more precise and we're able to better treat some of these adverse effects, I think patients are likely to benefit from these treatments not just from the quantity of life, but also from a quality-of-life perspective.

Transcript edited for clarity.

Case: A 75-Year-Old Woman with High-Risk Muscle Invasive Bladder Cancer

Initial presentation

• A 75-year-old woman with gross painless hematuria in August 2020

Patient history

• Diabetes and hypertension, both of which are managed with medications
• Current smoker 10 pack/year
• ECOG PS 0
• No family history of bladder cancer

Clinical workup and imaging

• eGFR 56 mL/min
• Patient undergoes TURBT and is found to have muscle invasive bladder cancer (MIBC)
• Patient undergoes chest, abdominal and pelvic imaging and a 1 cm external iliac lymph node is identified
• Clinical stage T3N1M0 urothelial carcinoma

Treatment

• Patient undergoes neoadjuvant treatment with gemcitabine + cisplatin for 4 cycles, followed by radical cystectomy in Jan. 2021.
• Patient undergoes imaging and lab work to monitor for disease progression.