GU Cancers 2022 | EV-103 Cohort H: neoadjuvant enfortumab vedotin monotherapy in cisplatin-ineligible MIBC
Daniel P. Petrylak, MD, Yale Cancer Center, New Haven, CT, discusses the Phase I/II EV-103 (NCT03288545) trial evalutating the long term benefits of enfortumab vedotin (EV) plus pembrolizumab for the first-line treatment of line locally advanced or metastatic urothelial carcinoma (la/mUC). The current first-line treatment options for patients with la/mUC are carboplatin-based regimens, however, patients demonstrate poor tolerability, limited durability, and moderate objective response rate (ORR). Inhibitors of PD-1/PD-L1 have shown durable responses in this patient population, although only approximately 24-29% of patients attain a response. The antibody-drug conjugate (ADC), EV, targets the delivery of monomethyl auristatin E (MMAE), a microtubule-disrupting agent, to tumor cells expressing Nectin-4. Previously treated patients with la/mUC have demonstrated an overall survival (OS) benefit compared to chemotherapy and preclinical studies have demonstrated MMAE utilizing ADCs can increase antitumor activity, instigating immunogenic cell death. EV-103 explored the treatment of patients with la/mUC who are ineligible for cisplatin-based regimens and demonstrated a durable response in the first-line setting. A Phase II study previously showed EV monotherapy achieved an ORR of 44% in patients with heavily-pre-treated mUC. In the EV-103 study, initial analysis of EV plus pembrolizumab confirmed an ORR of 71% in the first-line setting. These results suggested EV monotherapy and EV plus pembrolizumab may hold a place in the treatment of patients with muscle-invasive UC (MIU). Cohort H of the EV-103 study consisted of patients with MIUC. This patient population received EV monotherapy in the neoadjuvant setting on days 1 and 8 across a 21 day cycle. This interview took place at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium 2022 in San Francisco, CA.
Transcript (edited for clarity)
Cohort H comprised of those patients who are not eligible to receive cisplatin chemotherapy as neoadjuvant treatment. As we know neoadjuvant therapy for those patients who are eligible to receive cisplatin improves survival when compared to those patients who only receive cystectomy, and that serves to treat both the local tumor as well as the micrometastatic disease. So this study is affording those patients who are not eligible for cisplatin...
Cohort H comprised of those patients who are not eligible to receive cisplatin chemotherapy as neoadjuvant treatment. As we know neoadjuvant therapy for those patients who are eligible to receive cisplatin improves survival when compared to those patients who only receive cystectomy, and that serves to treat both the local tumor as well as the micrometastatic disease. So this study is affording those patients who are not eligible for cisplatin. And that comprises about 30 to 40% of all patients with local advanced urothelial carcinoma and affording the opportunity to receive a chemotherapy prior to having their cystectomy. So, enfortumab is an antibody-drug conjugate, which has been FDA approved in platinum-ineligible patients who have metastatic disease, as well as those patients who failed prior chemotherapy and an immune checkpoint therapy. Across the board enfortumab has about a 40% response rate. In this study, we found that 36% of patients had a complete pathological response after cystectomy and 50% of patients had down staging of their tumor, which is comparable to what we see with Cisplatin based chemo.
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