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Pembrolizumab Approved in Europe for Urothelial Carcinoma

Jason Broderick
Published: Tuesday, Sep 05, 2017

Treatment-related AEs occurring in ≥10% of participants were generally lower with pembrolizumab as opposed to chemotherapy, respectively, including for fatigue (13.9% vs 27.8%), nausea (10.9% vs 24.3%), diarrhea (9.0% vs 12.9%), asthenia (5.6% vs 14.1%), and anemia (3.4% vs 24.7% with chemotherapy).

The incidence of pruritus was higher in the pembrolizumab arm at 19.5% versus the chemotherapy group at 2.7%. Immune-related AEs that were higher with pembrolizumab compared with chemotherapy, respectively, included thyroid abnormalities (9.4% vs 1.6%), pneumonitis (4.1% vs 0.4%), and colitis (2.3% vs 0.4%).

Fifteen patients in the pembrolizumab arm and 28 patients in the chemotherapy group discontinued treatment due to a treatment-related AE. Each arm had 4 treatment-related deaths.

The phase II KEYNOTE-052 trial enrolled 370 patients with locally advanced or metastatic urothelial carcinoma who were deemed not eligible for cisplatin-containing chemotherapy. In the single-arm trial, pembrolizumab was administered at a flat 200 mg dose intravenously on day 1 of each 3-week cycle for up to 24 months.

The median age was 74 and 29% of the cohort was 80 or older. The primary tumor location was the lower tract for 81% of patients and 21% had liver metastases.

At median follow-up of 9.5 months, 7% of patients had a complete response, 22% had a partial response, and 18% had stable disease. More than 40% of patients in the study had progressive disease.

The response was consistent across demographic groups, including patients younger than 85 (29%; 95% CI, 20-35), patients ≥85 (28%; 95% CI, 15-44), and those with an ECOG performance status of 2 (27%, 95% CI, 20-35).

Among patients who had at least 1 post-baseline scan, 58% experienced a decrease in tumor lesions.

Median time-to-response was 2 months, and 82% of responses lasted at least 6 months. Median duration of response has not been reached.

Investigators created a training set of the first 100 patients enrolled to identify the 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 ≥10% was the optimal enrichment cutoff for predicting response.

In the training set, patients with a CPS <10% had an ORR of 17% with 3 complete responses and 8 partial responses. ORR was 37% for CPS-high patients with 4 complete responses and 7 partial responses.

Response was even stronger in the validation set. ORR was 51% for CPS-high patients, with 14 complete responses and 27 partial responses. ORR was 23% for CPS-low patients, with 5 complete responses and 37 partial responses.

Two-thirds of patients reported treatment-related AEs of any grade, with fatigue (18%), pruritus (17%), and rash (12%) being the most common. Seventy patients (19%) reported grade ≥3 AEs, including fatigue (2%) and colitis (2%). Other grade ≥3 AEs appeared in just 1% of patients. Investigators recorded a single treatment-related AE that resulted in death—myositis in an 83-year-old patient.


  1. O’Donnell PH, Grivas P, Balar AV, et al. Biomarker findings and mature clinical results from KEYNOTE-052: First-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC). J Clin Oncol. 35, 2017 (suppl; abstr 4502).
  2. Bellmunt J, de Wit R, Vaughn DJ, et al. Keynote-045: open-label, phase III study of pembrolizumab versus investigator’s choice of paclitaxel, docetaxel, or vinflunine for previously treated advanced urothelial cancer. Presented at: 2016 SITC Annual Meeting; November 9-13, 2016; National Harbor, MD. Abstract 470.

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