Vikas Kumar Singh, MD, medical oncologist, Baptist Health, discusses the potential benefit of the combination of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for the treatment of patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy.

FDA granted a priority review to supplemental biologics license applications for enfortumab vedotin and pembrolizumab

 for treatment as combiantion therapy in this patient population, based on the outcomes from the A, K, and dose-escalation cohorts evaluated in the phase 1b/2 KEYNOTE-869/EV-103 trial (NCT03288545).

The phase 1b/2 trial evaluated the combination therapy with a primary end point of confirmed overall response rate (ORR) by blinded independent central review, with secondary end points that included duration of response, overall survival (OS), and safety. Results from

dose escalation/cohort A demonstrated an ORR of 73.3%, and findings from cohort K presented at the 2022 ESMO Congress showed an ORR of 64.5% with a manageable safety profile.

Investigators are also evaluating enfortumab vedotin plus pembrolizumab in the ongoing phase 3 trial (NCT04223856), which is examining the combination vs chemotherapy alone in patients with previously untreated advanced urothelial cancer. The trial is enrolling patients who are both cisplatin eligible and cisplatin ineligible, Singh notes.

Currently, the standard of care for patients with previously untreated advanced urothelial cancer is chemotherapy followed by maintenance immunotherapy, Singh continues. However, the regimen consisting of enfortumab vedotin plus pembrolizumab could represent a non-chemotherapy option for this patient population, Singh says. If enfortumab vedotin plus pembrolizumab demonstrates a survival improvement vs chemotherapy for patients in the frontline setting, this regimen may be practice changing, Singh concludes.

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Vikas Kumar Singh, MD, discusses the potential benefit of the combination of enfortumab vedotin plus pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy.

Dr. Singh on the Continued Investigation of Enfortumab Vedotin/Pembrolizumab in Urothelial Cancer

Vikas Kumar Singh, MD, medical oncologist, Baptist Health, discusses findings from the phase 3 GETUG-AFU V05 VESPER (NCT01812369) and JAVELIN Bladder 100 (NCT02603432) trials in patients with bladder cancer.

Dr. Singh on Dose-Dense MVAC in Urothelial Carcinoma

The VESPER trial compared 2 common regimens for muscle-invasive bladder cancer: dose-dense MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], and cisplatin) and gemcitabine plus cisplatin, in the neoadjuvant and adjuvant settings, Singh says. Although these regimens are both standard treatments for bladder cancer, the head-to-head VESPER trial aimed to determine which is the superior perioperative therapy, Singh explains.

VESPER randomized patients to receive dose-dense MVAC or gemcitabine/cisplatin either before surgery (the neoadjuvant group) or after surgery (the adjuvant group). The primary end point of VESPER was progression-free survival (PFS) in patients who received perioperative chemotherapy with either dose-dense MVAC or gemcitabine plus cisplatin, Singh notes. This study did not meet its primary end point. In all patients in the study, the 3-year PFS rate was slightly improved in the dose-dense MVAC arm, at 64% vs 56% in the gemcitabine/cisplatin arm. Nevertheless, patients who received dose-dense MVAC had a longer time to progression, with a 3-year rate of 69% vs 58% in the gemcitabine/cisplatin arm.

However, in the neoadjuvant setting, dose-dense MVAC produced slightly higher 3-year PFS rates than gemcitabine plus cisplatin, at 66% vs 56%, respectively. The PFS data from this subgroup indicate that dose-dense MVAC may be more effective than gemcitabine plus cisplatin in the neoadjuvant setting, Singh says. Additionally, organ-confined response occurred more frequently in the dose-dense MVAC arm, at 77% vs 63% in the gemcitabine/cisplatin arm. The overall survival (OS) data for VESPER are still immature, Singh notes.

Dr. Singh on Avelumab Maintenance in Bladder Cancer

Findings from the JAVELIN Bladder 100 trial changed the standard of care for patients with metastatic urothelial cancer, Singh says. This study evaluated avelumab (Bavencio) maintenance therapy plus best supportive care (BSC) vs BSC alone in patients with metastatic urothelial carcinoma who had not progressed on prior first-line platinum-based chemotherapy, Singh explains.

Avelumab maintenance therapy led to an improved 1-year OS rate, at 71.3% vs 58.4% with BSC alone, Singh notes. The latest update from this trial, presented at the 2022 ASCO Genitourinary Cancers Symposium, showed that patients who received avelumab maintenance had a median OS of 23.8 months vs 15.0 months with BSC alone, Singh concludes.

Vikas Kumar Singh, MD, discusses findings from the phase 3 GETUG-AFU V05 VESPER (NCT01812369) and JAVELIN Bladder 100 (NCT02603432) trials in patients with bladder cancer.

Vikas Kumar Singh, MD

Articles

Dr. Singh on the Continued Investigation of Enfortumab Vedotin/Pembrolizumab in Urothelial Cancer

Dr. Singh on Treatment Updates in Urothelial Carcinoma