Padcev-Keytruda Combo Nearly Doubles Survival Time in Bladder Cancer

For patients with advanced bladder cancer, the standard of care has been platinum-based chemotherapy for decades, an expert told CURE®. However, an antibody-drug conjugate plus an immune checkpoint inhibitor now provides some patients with more options and potential survival benefits.

In a recent study from The New England Journal of Medicine, researchers included 886 patients with locally advanced or metastatic bladder cancer. This phase 3 worldwide study included two treatment arms: Padcev (enfortumab-vedotin) plus Keytruda (pembrolizumab) and chemotherapy alone.

Researchers evaluated patients in these arms to determine whether Padcev plus Keytruda would offer better survival outcomes than standard-of-care chemotherapy.

“It’s important to be aware of a seismic shift in terms of options that are available for patients with [bladder cancer],” study co-author Dr. Jean Hoffman-Censits told CURE®.

Hoffman-Censits is co-director of upper tract urothelial cancer multidisciplinary clinic and an associate professor of oncology at Johns Hopkins University School of Medicine.

“[Now,] there are other options that potentially may be more effective and even better tolerated and could be offered to a wider variety of patients,” she said.

The combination was approved by the Food and Drug Administration for advanced bladder cancer in December 2023.

Padcev-Keytruda Combination Versus Chemotherapy in Bladder Cancer

Other health conditions, known as medical comorbidities, play an important role when choosing treatment for bladder cancer, Hoffman-Censits noted. Preexisting medical comorbidities such as peripheral neuropathy (numbness in hands and feet), hearing or kidney function matter when considering chemotherapies.

Padcev and Keytruda may be good treatment options for patients with bladder cancer who may not tolerate chemotherapy well, she said. These drugs could help in terms when considering medical comorbidities patients have, notably because the drugs are “designed differently.”

Hoffman-Censits emphasized that another major difference between the combination and platinum-based chemotherapy regimen stem from survival outcomes.

Overall survival was improved in patients who received Padcev plus Keytruda, she said. Regarding improved survival benefits, she considered this a “gold standard benchmark.” Overall survival is the time from diagnosis when a patient is alive, regardless of their cancer status, according to the National Cancer Institute.

The median overall survival in patients who received Padcev plus Keytruda was 31.5 months, the study stated. This was compared with a median overall survival of 16.1 months for patients who received chemotherapy.

“To see a number that is that long for patients with [bladder cancer], those are the metrics that we have not seen before with this disease,” Hoffman-Censits explained. “It’s so incredibly important to have those numbers. And to see that kind of survival benefit is [also] unlike anything we’d seen before.”

Progression-free survival was also improved for patients who received Padcev and Keytruda. Progression-free survival is the time patients live from diagnosis to the end of treatment the cancer does not worsen or spread, the National Cancer Institute defines.

According to the study, patients in the Padcev-Keytruda arm had progression-free survival for a median of 12.5 months. Patients who received chemotherapy alone had a progression-free survival of 6.3 months.

READ MORE: Immunotherapy Improves Survival in Metastatic Bladder Cancer

Differences in Treatment Side Effects for Bladder Cancer

Regardig side effects, Hoffman-Censits stated that patients should not feel “so sick or so tired [that they] can’t come in for regular appointments, labs, visits or scans. If patients feel too sick to see their doctor, usually by definition, they need to be seen.”

She addressed some of the common side effects patients with bladder cancer may experience, whether they received Padcev plus Keytruda or chemotherapy.

Peripheral neuropathy, Hoffman-Censits explained, is a common side effect of both treatment options.

Specifically with chemotherapy, “fatigue, and fatigue that can cause high blood sugar, and diabetes are the more common [side effects],” she said. “We often see decreases in blood counts, like decreases in white blood cells, red blood cells and the platelets.”

She explained that “white blood cells fight infection, red blood cells are hemoglobin that carry oxygen in the bloodstream and platelets contribute to clotting blood.”

It’s important for patients to actively communicate, Hoffman-Censits noted, when mitigating side effects.

“If patients have side effects, I encourage them to communicate with their clinical nursing staff, infusion nurses as a touch point, physician extenders within the clinic and the physicians in the clinic,” she said.

“[Early and] great lines of communication about those side effects can help [patients’] teams work to mitigate some of the toxicity with the hopes that with additional supportive care or even with breaks,” Hoffman-Censits added. “There are always periods where treatment teams have to make decisions based on not only laboratory findings, bit also clinical assessment of how each person is doing during treatment.”

Patients’ schedules and dosing schedules, along with treatment modifications to cater to the patient are considered, she explained. Other factors include adding other medications that may help patients and how the team can maximize treatment for each patient.

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