Journal
CLINICAL CANCER RESEARCH
Volume 27, Issue 15, Pages 4195-4204Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-4301
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Funding
- Merck Sharp Dohme Corp.
- Merck Co., Inc.
- Kenilworth, NJ
- Henry L. Hillman Foundation
- Cancer Center Support grant [P30CA04790]
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Neoadjuvant concurrent HDI and pembrolizumab therapy showed promising clinical activity in resectable advanced melanoma patients, despite high rates of treatment discontinuation. Pathologic complete response was identified as a prognostic indicator.
Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFN alpha-2b (HDI) therapy in patients with resectable advanced melanoma. Patients and Methods: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m(2)/day i.v., 5 days per week for 4 weeks, then 10 MU/m(2)/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery. Results: A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5-85.8], with a 43% (95% CI: 273-60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively). Conclusions: Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.
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