Enfortumab vedotin shows potential for urothelial cancer
The antibody-drug conjugate enfortumab vedotin (EV) demonstrated a promising overall response rate (ORR) in patients with metastatic urothelial cancer (mUC), including those who had liver metastases and prior treatment with checkpoint inhibitors, according to the phase 1 data of the EV-101* trial presented at ASCO 2018.
A total of 112 patients (median age 67 years, 73 percent male) with mUC who had received prior chemotherapy (94, 29, and 79 percent for platinum-based, taxane, and checkpoint inhibitor treatment, respectively) or were ineligible for cisplatin were given a 30-minute infusion of EV at 1.25 mg/kg (days 1, 8, and 15 every 28 days). Primary tumour site was the bladder (77 percent). [ASCO 2018, abstract 4504]
At baseline, nearly 50 percent had lung metastases, while 29 and 19 percent had liver and lymph node metastases, respectively. Nearly 80 percent discontinued, with 56 percent attributed to clinical or radiographic progression.
Median time to first response was 1.68 months, while median duration of response was 5.75 months.
There was a clinically significant ORR of 41 percent, which the researchers indicated as an ‘encouraging’ result as it reflects EV’s potential in targeting nectin-4, which is highly expressed in solid tumours such as urothelial cancers.
Disease control rate (DCR) was 71 percent, while complete and partial responses (CR and PR, respectively) were 4 percent and 37 percent, respectively.
Subgroup analysis of patients with a history of checkpoint inhibitor use and liver metastases revealed similar ORRs of 40 percent and 39 percent, respectively, while DCRs were 74 percent and 61 percent, CR rates were 3 percent and 0 percent, and PR rates were 37 percent and 39 percent.
Progression-free survival for all patients regardless of prior checkpoint inhibitor exposure was 5.4 months.
Median overall survival (OS) was 13.6 and 14.0 months in the overall population and among those with prior checkpoint inhibitor exposure, respectively. Estimated OS rates at 6 and 12 months are 74.4 percent and 56.3 percent, respectively.
“Although OS data are still maturing, the preliminary median OS … is encouraging, given the historical median OS for checkpoint inhibitors reported between 8.9 and 10.3 months in patients after platinum-based chemotherapy,” said the researchers.
Most adverse events (AEs) were mild to moderate in severity, the most common being fatigue (54 percent), followed by alopecia (45 percent), and decreased appetite (40 percent). The most common grade ≥3 AEs were anaemia (8 percent), hyponatremia (7 percent), urinary tract infection (7 percent), and hyperglycaemia (6 percent, 3.6 percent of which were serious cases). Five percent of patients had fatal treatment-related AEs (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, and multiple organ failure).
Nonetheless, EV was well tolerated overall and has been conferred a ‘breakthrough therapy’ designation by the US Food and Drug Administration for patients with mUC who have previously received immune checkpoint inhibitors, said the researchers. In addition to the survival data awaiting maturity, three other studies on EV are ongoing to further elucidate the role of EV in urothelial cancer treatment, they added.