As reported by Elizabeth R. Plimack, MD, of Fox Chase Cancer Center, Temple Health, and colleagues in The Lancet Oncology, pembrolizumab (Keytruda) has shown activity in patients in the locally advanced or metastatic urothelial carcinoma cohort included in the phase Ib KEYNOTE-012 trial.
In the study, 33 patients with locally advanced or metastatic urothelial cancer, including cancers of the renal pelvis, ureter, bladder, or urethra, with programmed cell death ligand 1 (PD-L1) expression of ≥ 1% on tumor cells or tumor stroma as determined by immunohistochemistry, were enrolled from 8 sites in the United States and Israel. Pembrolizumab was given intravenously at 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or the end of the study (ie, 24 months of treatment).
There was no limit to the number of previous treatments; 52% had received at least 2 treatments for advanced disease, and 61% had received neoadjuvant or adjuvant therapy. All 33 patients received 1 dose of study drug (safety population); 27 patients were considered evaluable for response.
Response Rate
Median follow-up was 13 months. Response was observed in 7 of 27 assessable patients (26%, 95% confidence interval [CI] = 11%–46%), including a complete response in 3 patients (11%, 95% CI = 2%–29%) and a partial response in 4 patients (15%, 95% CI = 4%–34%); 4 patients (15%) had stable disease. Median time to response was 2 months, and median duration of response was 10 months (range = 4–22+ months, with 2 responses ongoing at data cutoff). Responses were ≥ 6 months in 4 responders and > 12 months in 3 responders.
Adverse Events
The most common treatment-related adverse events of any grade were fatigue (18%) and peripheral edema (12%). Grade 3 treatment-related adverse events occurred in 15% of patients, with no event occurring in more than 1 patient. Serious treatment-related adverse events occurred in 9%.
Potential immune-related adverse events occurred in 18% of patients, including grade 2 and grade 3 myositis, grade 2 uveitis, grade 3 colitis, grade 3 pruritic rash, grade 3 maculopapular rash, grade 3 stasis dermatitis, and grade 3 rhabdomyolysis. None of the four deaths occurring during the study (due to cardiac arrest, pneumonia, sepsis, and subarachnoid hemorrhage) were considered related to treatment.
The investigators concluded: “Pembrolizumab showed anti-tumour activity and acceptable safety in patients with advanced urothelial cancer, supporting ongoing phase 2 and 3 studies of pembrolizumab in this population.”
The investigation was funded by Merck & Co, Inc.
