Considering Treatment Sequencing After mUC Recurrence: Does Real-World Data Hold the Answers?

Karine Tawagi, MD, University of Illinois College of Medicine, provides her thoughts on treatment selection and sequencing for metastatic urothelial carcinoma, especially after progression on frontline EV/pembrolizumab.

Additionally, she weighs in on the real-world safety data pertaining to patients with locally advanced or metastatic urothelial carcinoma treated with sacituzumab govitecan.

Lastly, Dr. Tawagi comments on whether the treatment guidelines have caught up to the efficacy and safety data available for all of these options.

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What are your thoughts on treatment selection and sequencing for metastatic urothelial carcinoma? With EV/pembrolizumab moving into the frontline setting, how do we make sense of treatment sequencing after recurrence?

Dr. Tawagi: I believe this is a question that is at the forefront of everyone’s mind, especially following that groundbreaking ESMO presentation. I speculate there could be a role for chemotherapy in the second-line setting, specifically platinum-based chemotherapy such as gemcitabine. However, a significant query remains regarding the eligibility of patients for cisplatin if they exhibit residual neuropathy from prior EV/pembro treatment. Alternatively, carboplatin with gemcitabine remains an available option.

Moving forward, if one opts for the chemotherapy route, the question arises: does maintenance avelumab hold any significance? We’ve observed that IO rechallenge in other disease states, such as kidney cancer, has yielded unsuccessful results. Presently, there are ongoing trials examining sacituzumab govitecan with or without immunotherapy in the second-line setting. It is particularly intriguing to observe how these trials unfold, considering the potential differences in bladder cancer biology regarding immunotherapy or rechallenge.

Another pressing inquiry revolves around the role of sacituzumab govitecan, either independently or in combination with other agents, in ongoing trials. In the frontline setting, chemotherapy boasts response rates of approximately 44%. Conversely, sacituzumab govitecan has demonstrated response rates of around 27% in its approved line of treatment. The lingering question is whether it will perform similarly in the post-EV/pembro setting – a query that remains unanswered.

Lastly, for patients harboring FGFR3 mutations or amplifications, the effectiveness of erdafitinib in the post-EV/pembro setting is under scrutiny.

How will these questions be answered? How will it be determined which option is best for a given patient?

Dr. Tawagi: In an ideal world, having comparative data in this setting would be optimal. However, considering the current landscape, it appears we will conduct individual trials for certain questions to assess the efficacy of each class. Consequently, when it comes down to it, we will have to decide on a regimen without the benefit of comparative data, relying instead on the outcomes of these separate trials.

How do you weigh the real-world safety data pertaining to patients with locally advanced or metastatic urothelial carcinoma treated with sacituzumab govitecan?

Dr. Tawagi: This abstract presents intriguing findings as it examines real-world data regarding the safety profile of sacituzumab govitecan. The study included approximately 86 patients, with 65% having received EV as their immediate prior line of therapy, and a total of 71% having received EV at any point before sacituzumab govitecan. The researchers observed similar toxicity profiles to those reported in the TROPHY-U-01 trial, which led to the approval of sacituzumab govitecan. Common adverse events included neutropenia and gastrointestinal toxicity. Notably, approximately 25% of patients in the real-world setting received primary granulocyte-colony stimulating factor (G-CSF) prophylaxis with sacituzumab govitecan, and none of these patients experienced severe neutropenia. These findings are valuable for navigating the process of obtaining insurance approval for G-CSF in conjunction with sacituzumab govitecan therapy.

Another noteworthy aspect of this abstract is that only half of the patients required dose modifications, while the remainder were able to maintain the standard 10 mg/kg dosage on days 1 and 8 of the 21-day cycle throughout their treatment with sacituzumab govitecan. Although efficacy data specific to this abstract are lacking, the insights provided into the real-world toxicity profile, particularly in the post-EV setting, are significant as we consider the use of sacituzumab govitecan following EV/pembro therapy.

Have the treatment guidelines caught up to the efficacy and safety data available for all of these options?

Dr. Tawagi: I believe there is still room for improvement in terms of guidelines, particularly concerning the management of toxicity associated with antibody drug conjugates. This marks a new era in cancer treatment, and it is crucial to establish guidelines akin to those for checkpoint inhibitors. With checkpoint inhibitors, we have well-established guidelines readily providing instructions for managing toxicity across different grades (1 through 4), including when to initiate interventions such as topical or systemic steroids depending on the severity of the toxicity. It is essential to replicate this approach for antibody drug conjugates to instill more confidence in their use, not only in academic settings but also in community healthcare settings.