From the Journals

PD-L1 positivity correlated with pembrolizumab response in advanced melanoma

Publish date: October 13, 2016

Programmed death ligand–1 expression correlated positively and significantly with pembrolizumab response in advanced melanoma, based on an analysis of 405 patients from the international, multicohort, open-label phase I KEYNOTE-001 trial.

Among patients for whom 33%-65% of tumor cells expressed PD-L1, the objective rate of response was 57%, but the rate was only 8% among patients whose specimens did not express PD-L1, Adil Daud, MD, of the University of California, San Francisco, and associates reported. Taken together, the findings suggest that melanoma is most likely to respond to pembrolizumab when specimens show at least 10% positivity, the investigators reported (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.67.2477).

Dr. Adil Daud

KEYNOTE-001 included 655 patients with ipilimumab-naive, ipilimumab-treated, or ipilimumab-refractory melanoma who received pembrolizumab dosed at 2 mg/kg once every 3 weeks, 10 mg/kg once every 3 weeks, or 10 mg/kg once every 2 weeks. The investigators assessed tumor response every 12 weeks using RECIST v1.1 criteria, and quantified PD-L1 expression in pretreatment tumor specimens by using the commercially available PD-L1 IHC 22C3 pharmDx assay. A total of 451 patients had specimens that were evaluable for PD-L1 expression, of which 24% of specimens were PD-L1 negative and 76% were PD-L1 positive.

Among the 405 patients who also were evaluable for tumor response, the overall objective response rate was 33% (95% confidence interval, 28%-37%). Grouping patients based on the melanoma scoring system for PD-L1 expression showed that PD-L1 positivity correlated significantly with the objective response rate (P less than .001). Furthermore, a higher PD-L1 melanoma score correlated significantly with both progression-free survival (hazard ratio, 0.76; 95% CI, 0.7-0.82) and overall survival (HR, 0.76; 95% CI, 0.69-0.83), with P values less than .001 for each association.

Median progression-free survival was 5.6 months in PD-L1–positive patients and 2.8 months in PD-L1–negative patients, while median overall survival was 30 months in PD-L1–positive patients and 12.6 months in PD-L1–negative patients, the researchers reported. “The high prevalence of PD-L1 positivity observed in this study, along with the durable responses observed in PD-L1–negative tumors, suggest that pembrolizumab treatment should not be limited to patients with PD-L1–positive tumors,” they concluded. “Ongoing clinical trials with correlative studies will further delineate the role of PD-L1 expression in melanoma.”

Merck sponsored the trial. Dr. Daud disclosed ties to Merck, OncoSec, Novartis, Genentech, Bristol-Myers Squibb, and Array BioPharma.

PD-L1 positivity correlated with pembrolizumab response in advanced melanoma

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