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Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012.
Background: Pembrolizumab, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in patients with recurrent or metastatic PD-L1–positive urothelial cancer enrolled in the phase 1b KEYNOTE-012 study (NCT01848834). We present updated efficacy and safety data for these patients, as well as an analysis of the relationship between PD-L1 expression and ORR. Methods: Eligible patients had recurrent, metastatic, or persistent urothelial cancer of the bladder, renal pelvis, ureter, or urethra. Patients received pembrolizumab 10 mg/kg every 2 weeks until complete response, progression, or unacceptable toxicity. PD-L1 expression was evaluated in baseline tumor samples at a central laboratory. Patients were enrolled if there were ≥1% PD-L1–positive cells in tumor nests or a PD-L1–positive band in stroma by a prototype immunohistochemistry assay. Samples were also analyzed with the clinical trial immunohistochemistry assay. Response was evaluated every 8 weeks per RECIST v1.1 by central review. Results: Thirty-three patients were enrolled (median age, 70 years; ≥3 prior therapies, 33%; visceral or osseous metastases, 66%). Median follow-up duration was 13 months (range, 1-16). Grade 3-4 drug-related adverse events occurred in 5 (15%) patients. In the 28 patients with measurable disease at baseline, ORR was 25% (95% CI 11-45), with 3 (11%) complete and 4 (14%) partial responses per central review. At the time of analysis, median duration of response had not been reached (range, 16-50+ weeks). The 12-month PFS rate was 19%. ORR in patients with tumors positive for PD-L1 expression as assessed with the clinical trial assay was 38%. Conclusions: Pembrolizumab demonstrates durable antitumor activity in patients with advanced urothelial cancer. A higher response rate was seen in patients with PD-L1 expression. Further analysis of the relationship between response and predictive biomarkers is ongoing. Clinical trial information: NCT01848834
Abstracts by Elizabeth R. Plimack:
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