For patients with cisplatin-ineligible advanced urothelial cancer, frontline treatment with Keytruda (pembrolizumab) showed long-lasting response, according to updated phase 2 results from the KEYNOTE-052 trial.
As of the December 2016 data cutoff, the overall objective response rate (ORR) was 29 percent with a clinical benefit rate of 47 percent. Peter H. O’Donnell, M.D., assistant professor of medicine at the University of Chicago, presented the results at the 2017 ASCO Annual Meeting.
“The overall objective response rate represents a 5 percent increase over the rate that has been previously reported,” O’Donnell said. “These results confirm that first-line pembrolizumab elicits clinically meaningful and durable antitumor activity in cisplatin-ineligible patients with metastatic urothelial cancer.”
In KEYNOTE-052, 370 patients with advanced, unresectable, or metastatic disease who were ineligible for treatment with cisplatin were assigned to 200 mg of Keytruda every three weeks. Patients continued treatment for two years, or until progression, toxicity or withdrawal.
The median age was 74 and 29 percent of the cohort was 80 or older. The primary tumor location was the lower tract for 81 percent of patients and 21 percent had liver metastases.
At median follow-up of 9.5 months, 7 percent of patients had a complete response, 22 percent had a partial response, and 18 percent had stable disease. More than 40 percent of patients in the study had progressive disease.
O’Donnell said the response was consistent across demographic groups, including patients younger than 85 (29 percent), patients 85 or older (28 percent), and those with an ECOG performance status of 2 (27 percent).
Among patients who had at least one post-baseline scan, 58 percent experienced a decrease in tumor lesions.
Median time-to-response was two months, and O’Donnell said 82 percent of responses lasted at least six months. Median duration of response has not been reached.
Investigators created a training set of the first 100 patients enrolled to identify the combined positive score (CPS) cut point for PD-L1 expression and a validation set that included all patients except for that first 100 to confirm results. Investigators found that a CPS over 10 percent was the optimal enrichment cutoff for predicting response.
In the training set, patients with a CPS less than 10 percent had an ORR of 17 percent with three complete responses and eight partial responses. ORR was 37 percent for CPS-high patients with four complete responses and seven partial responses.
Response was even stronger in the validation set. ORR was 51 percent for CPS-high patients, with 14 complete responses and 27 partial responses. ORR was 23 percent for CPS-low patients, with five complete responses and 37 partial responses.
Two-thirds of patients reported treatment-related adverse events (AEs) of any grade, with fatigue (18 percent), pruritus (17 percent) and rash (12 percent) being the most common.
Seventy patients (19 percent) reported grade 3 or higher AEs, including fatigue (2 percent) and colitis (2 percent). Other grade 3 or higher AEs appeared in just 1 percent of patients.
“Importantly, only 7 percent of patients discontinued treatment because of a treatment-related adverse event,” O’Donnell said. “This is a rate that would be approximately one-third of that traditionally described for gemcitabine/carboplatin.”
Investigators recorded a single treatment-related AE that resulted in death—myositis in an 83-year-old patient.
O’Donnell added that the rate of immune-mediated AEs was similar to those reported in previous anti–PD-1 studies.
These results update findings first presented at the 2016 ESMO Congress. At the time, overall ORR was 24.0 percent at a median follow-up of eight months. There were six complete responses, 17 partial responses, and 15 patients with stable disease. Forty-eight patients experienced disease progression.
Based on data from the KEYNOTE-052 trial, the FDA granted an accelerated approval in May 2017 for the accelerated approval to frontline Keytruda for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.