ASCO 2017: Biomarker findings and mature clinical results from KEYNOTE-052: First-line pembrolizumab in cisplatin-ineligible advanced urothelial cancer

Chicago, IL ( Comorbidities and renal impairment preclude many patients with advanced urothelial carcinoma (UC) from receiving chemotherapy. Initial results from the phase 2 KEYNOTE-052 (NCT02335424) trial suggested first-line Pembrolizumab (pembro) is active and safe in cisplatin-ineligible advanced UC patients. 

The KEYNOTE-052 study recruited advanced urothelial cancer patients with nor prior chemotherapy for metastatic disease, who were ECOG 0-2, and ineligible for cisplatin therapy (ECOG PS 2, CrCl ≥30 - < 60 mL/min, grade ≥2 neuropathy/hearing loss, NYHA Class 3 heart failure). These patients were given pembro 200 mg IV every 3 weeks for a duration of 24 months or until confirmed disease progression, intolerable toxicity or patient withdrawal. Imaging was performed at week 9, then every 6 weeks for the first year, and every 12 weeks thereafter. Primary end point was confirmed objective response rate (ORR) (RECIST v1.1, independent review). Efficacy and safety were assessed. The associations of an 18-gene expression profile (GEP) and immunohistochemistry (IHC) PD-L1 combined positive score (CPS) with ORR were evaluated as well. 

Dr. O'Donnell presented updated efficacy and safety data for patients with at least 6 months of follow-up. Additionally, data regarding correlation of biomarkers to outcomes were presented. 

Overall 370 patients were enrolled with a median age of 74 (range 34-94) with 29% being over the age of 80, and 77% of them being men. The updated results showed an ORR of 29% (95% CI, 24-34) with 27 (7%) and 81 (22%) pts achieving complete and partial responses, respectively. Another 68 pts (18%) had stable disease as best response, for a clinical benefit rate of 47%. Median time to response was 2 months (range, 1-9). Median duration of response was not reached, and 82%% of responses lasted more than 6 months. At data cut off 67% of responses were ongoing. Any-grade and grade ≥3 drug-related adverse events (AEs) occurred in 239 (65%) and 68 (18%) patients, respectively. Immune-mediated AEs occurred in 76 (21%) pts. Evidence supporting a positive association with response was seen in the first 100 pts for both biomarkers (GEP, n = 72, P = 0.007, ROC AUC 0.69; and CPS, n = 96, P= 0.111, ROC AUC 0.58). ORR in the 110 pts with CPS ≥10% was 51% (95% CI, 38-57). 

In summary, this analysis confirms that pembro elicits clinically meaningful, durable responses in cisplatin-ineligible advanced UC disease, with a 29% ORR in all patients. Consistent with PD-1 pathway biology, CPS>=10% was determined to be the optimal enrichment cutoff for predicting response. There was a 55% ORR in the CPS>=10%. Importantly, Pembro was well tolerated across cisplatin-ineligible pts, including elderly and pts with poor performance status. 

Presented By: Peter H. O'Donnell, The University of Chicago Medical Center, Chicago, IL

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
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