Trodelvy-Keytruda Combo Shows High Promise in Metastatic Bladder Cancer

Treatment with a combination of Trodelvy and Keytruda may provide a "synergistic effect" for patients with metastatic bladder cancer.

The treatment of Trodelvy (sacituzumab-govitecan), which is a form of “targeted chemotherapy, plus Keytruda, which is a form of immunotherapy in patients with metastatic bladder (urothelial) cancer who experienced progression (worsening or further spreading) on or after receiving first-line platinum-based chemotherapy showed a high overall response rate with a relatively tolerable safety profile, according to a recent trial published in the Journal of Clinical Oncology.

These results were based on findings from cohort 3 of a phase 2 trial TROPHY-U-01, which included 41 patients — the median age was 67 and 83% identified as male, the study reported — of which all patients received the Trodelvy-Keytruda combination.

Data from laboratory-based studies suggested that this combination would possibly have “potential synergism,” Dr. Petros Grivas told CURE®, which may offer benefits for the respective patient population.

Grivas is a board-certified medical oncologist and the clinical director of the genitourinary cancers program at Fred Hutchinson Cancer Center and the University of Washington.

This trial’s primary endpoint (main result measured at the end of a study to see if treatment worked) was the overall response rate (ORR), or the percentage of patients whose cancer shrunk significantly or completely diminished after treatment, according to the National Cancer Institute.

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Researchers determined that the ORR was 41% at a median follow-up of 14.8 months, with a complete response rate of 20%. These data reflect that the primary endpoint of ORR was met, according to Grivas.

The median (relative average) duration of response was 11.1 months, the median progression-free survival (time before cancer worsens or results in death) was 5.3 months and the median overall survival (time patients live) was 12.7 months, according to this particular trial setting.

Although these results reflect a promising and encouraging signal for this patient population, Grivas noted that they do not change clinical practice and “take them with a grain of salt because of the single arm design,” which means that this combination regimen was not compared directly to another treatment.

Still, because of the success of the phase 2 trial, Grivas shared that they are soon “moving to a larger phase 3 trial, which is a very exciting thing.”

He noted that the phase 3 trial will be comparing two treatment regimens: Trodelvy plus Keytruda versus Trodelvy alone. Patients eligible for this upcoming larger trial have metastatic bladder cancer and have experienced cancer progression/worsening after previously receiving immunotherapy and possibly other therapies, Grivas said. This upcoming phase 3 trial is set to launch later in 2024.

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In terms of side effects, the study reported that all 41 patients experienced at least one treatment-emergent side effect (occurring after starting treatment, regardless of cause) and at least one treatment-related side effect (caused by treatment).

Some of the most common treatment-related side effects included diarrhea (71%), nausea (56%), neutropenia (51%; low levels of neutrophils, which belong to white blood cells), anemia (49%), physical weakness (41%), hair loss (39%), fatigue (32%), vomiting (29%) and decreased appetite (29%), the trial noted.

The researchers also reported that 46% of patients had Trodelvy dose interruption/delay due to treatment-related side effects, 39% of patients had to reduce Trodelvy dose and 15% of patients discontinued Trodelvy treatment due to side effects. Of note, no death attributed to side effects occurred in this trial cohort.

Grivas encourages patients to talk with their providers about the topic of clinical trials as a potential therapy option, depending on their eligibility.

“In general, I think it's very important to ask the treating providers if they have reviewed the most recent available data and specifically the approved therapy options, and we also need to make sure that patients have access to approved therapies in an equitable manner,” Grivas said. “And that's an important issue across the globe — equitable access to therapies that have shown benefit is very important. We must remove barriers and address the issue of health care disparities, which is important and relevant.”

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