Patients with locally advanced or metastatic urothelial cancer, a type of bladder cancer, experienced improvements in progression-free survival (PFS) and overall survival (OS) when treated with Padcev (enfortumab vedotin-ejfv) plus Keytruda (pembrolizumab) versus platinum-based chemotherapy without negative impact to quality of life (QOL), pain or functioning, according to patient-reported outcome (PRO) data from the phase 3 EV-302 trial.
In total, the EV-302 trial enrolled 886 patients with locally advanced or metastatic urothelial cancer who were assigned to receive either Padcev and Keytruda (442 patients) or to receive platinum-based chemotherapy (444 patients). All patients included in the trial were treated until disease progression, unacceptable toxicity or the completion of maximum cycles.
Study Highlights:
- The combination of Padcev (enfortumab vedotin-ejfv) and Keytruda (pembrolizumab) for patients with locally advanced or metastatic urothelial cancer helped patients live longer overall (overall survival) and live longer without their disease worsening (progression-free survival), compared to chemotherapy.
- The combination of Padcev and Keytruda did not negatively impact patients’ quality of life, pain levels or functioning.
- Patients given Padcev and Keytruda lived for a longer period of time before their pain progressed compared to those given chemotherapy.
Previously reported data from the EV-302 trial showed that the combination of Padcev and Keytruda nearly doubled PFS (the time a patient lives without their disease spreading or progressing) and OS (the time a patient lives, regardless of disease status) when compared with chemotherapy in patients with locally advanced or metastatic urothelial cancer.
Specifically, the median PFS was 12.5 months with Padcev and Keytruda, versus 6.3 months in the chemotherapy group. The median OS was 31.5 months in the Padcev and Keytruda group, compared with 16.1 months in the chemotherapy group.
Updated data from the EV-302 trial were presented at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting by Dr. Shilpa Gupta, director of Genitourinary Medical Oncology at Taussig Cancer Institute and co-leader of the Genitourinary Oncology Program at Cleveland Clinic.
“We know that patients with locally advanced and metastatic urothelial cancer have a poor prognosis, with an estimated five-year survival of less than 8% globally. And they have a high symptom and pain burden, which impacts their quality of life and functioning,” Gupta noted during the presentation. “Here, we report the PRO data from the EV-302 trial, including impacts on patient’s quality of life, functioning and disease symptoms.”
At the start of the trial, QOL and pain scores were similar among patients in the two treatment groups.
Time to pain progression (TTPP) was previously reported, showing a median TTPP of 14.2 months in the Padcev and Keytruda group and 10 months in the chemotherapy group. No statistically significant difference between the two groups was observed, meaning that researchers could not say with certainty that one treatment regimen truly led to a superior outcome.
Further, patients in the Padcev and Keytruda group demonstrated larger improvements in worst pain per the Brief Pain Inventory Short Form (BPI-SF) assessment compared with those in the chemotherapy group. However, neither group reached the pre-defined thresholds for a clinically meaningful improvement.
Among those with moderate/severe pain at baseline (approximately one-third of patients), a clinically meaningful improvement in worst pain per BPI-SF was observed in both treatment groups. The BPI-SF is a questionnaire used to measure how pain affects a patient’s daily functioning in tasks like mood, walking ability, work, relationships, sleep and enjoyment of life. Those in the Padcev and Keytruda group experienced greater improvements in pain compared with those in the chemotherapy group.
The investigators also assessed changes in the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), which measures global health status (GHS; overall patient wellbeing) and QOL.
Patients in the Padcev and Keytruda group demonstrated a worsening in GHS/QOL score at week 3, with a return to baseline at week 4. Patients in the chemotherapy group demonstrated a worsening in GHS/QOL from week 1 through week 17, with a return to baseline from week 20. Overall, the median time to confirmed deterioration was 5.9 months in the Padcev and Keytruda group versus 3.2 months in the chemotherapy group.
Among those with moderate/severe pain at baseline, patients in the Padcev and Keytruda group showed a clinically meaningful improvement in GHS/QOL compared with the chemotherapy group. Both cisplatin-eligible and cisplatin-ineligible patients in the Padcev and Keytruda group showed a transient worsening in GHS/QOL through week 3, with a return to baseline at week 4. Padcev and Keytruda appeared to perform better in cisplatin-eligible patients compared with chemotherapy.
Additionally, patients in the Padcev and Keytruda group demonstrated improved functioning across all functioning domains in the EORTC QLQ-C30 assessment compared with those in the chemotherapy group, assessed by a change from baseline to week 26.
Safety data from the EV-302 study was consistent with previous studies and showed that Padcev and Keytruda was generally manageable.
Gupta concluded in the presentation, “The PRO data presented here complements the published clinical efficacy and safety data, add the patient’s voice and support the use of [Padcev and Keytruda] for patients with locally advanced/metastatic urothelial cancer.”
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