Highlights from

ASCO 2019

American Society of Clinical Oncology annual meeting

Chicago, USA 31 May - 4 June 2019

Enfortumab vedotin increases survival in urothelial cancer patients

A single arm, multi-centre phase 2 clinical trial of 125 patients showed that treatment with enfortumab vedotin (EV) – a new agent targeting the nectin-4 protein found in 97% of urothelial cancers – produced responses in 44% of patients with locally advanced or metastatic forms of urothelial cancer; 12% had a complete response. Patients had previously been treated with platinum chemotherapy and a PD-1 or PD-L1 immune checkpoint inhibitor, but the cancer had progressed despite these treatments. Among those patients with cancer that had not previously responded to a checkpoint inhibitor, 41% responded to EV and, notably, 38% of people with cancer that had metastasised to the liver responded [1].

“These phase 2 results replicate the phase 1 results very closely, which is not often the case in clinical trials,” said presenting author Prof. Daniel P. Petrylak (Yale Cancer Center, USA). “The fact that we have a therapy that can help people who don’t benefit from checkpoint inhibitors is very gratifying.”

For phase 2, investigators enrolled urothelial patients who had been treated with platinum-based chemotherapy and/or checkpoint inhibitors to two groups: group one had been previously treated with both medicines, and group two consisted of people who had not received platinum chemotherapy. Only results from the first group are currently being reported. In group one, 70% of patients enrolled were male and the median age was 69; 35% of people had cancers in their upper urinary tract, a relatively uncommon site; and patients had a median of 3 prior systemic treatments in the locally advanced or metastatic setting but had not received treatment for at least 2 weeks prior to enrolling in this trial.

In total, 44% of people responded to EV resulting in either no growth or shrinkage in their tumours, and 12% had a complete response with no detectable sign of cancer. The median overall survival time was 11.7 months. Among those patients with cancer that had not responded to a checkpoint inhibitor, 41% responded to EV, and 38% of people with cancer that had metastasised to the liver responded to EV. EV was well-tolerated among patients enrolled in the trial. The most common side effects included fatigue (50%), alopecia or hair loss (49%), rash (48%), and decreased appetite (44%).

A phase 3 study to confirm these findings is now underway. Group two is still enrolling people in the trial, and there is also a trial in progress to look at the benefits of providing EV for people newly diagnosed with advanced urothelial cancer. The trial is studying EV in combination with pembrolizumab, and EV in combination with a platinum-based chemotherapy.

  1. Petrylak DP et al. Abstract LBA4505. EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors. ASCO 2019, 31 May-4 June, Chicago, USA.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.