Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1–Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study

Abstract

Purpose To establish the safety profile and antitumor activity of the anti-programmed death 1 receptor monoclonal antibody, pembrolizumab, in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that expressed programmed death-ligand 1 (PD-L1). Patients and Methods KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors. Key eligibility criteria for the NPC cohort included unresectable or metastatic disease, failure on prior standard therapy, and PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes. Patients received pembrolizumab 10 mg/kg every 2 weeks up to 2 years or until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR) per investigator review. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) every 8 weeks for the first 6 months and every 12 weeks thereafter. Results Twenty-seven patients received pembrolizumab. Median age was 52.0 years (range, 18 to 68 years); 92.6% received prior therapies for RM-NPC; 70.4% had received three or more therapies. Partial response and stable disease were observed in seven and 14 patients, respectively, for an ORR of 25.9% (95% CI, 11.1 to 46.3) over a median follow-up of 20 months. ORR by central review was similar (26.3%). Drug-related adverse events that occurred in 15% or more of patients included rash (25.9%), pruritus (25.9%), pain (22.2%), hypothyroidism (18.5%), and fatigue (18.5%). Grade ≥ 3 drug-related adverse events occurred in eight patients (29.6%), and there was one drug-related death (sepsis). As of the data cutoff (June 20, 2016), two patients remained on pembrolizumab treatment. Conclusion Pembrolizumab demonstrated antitumor activity and a manageable safety profile in patients with RM-NPC.

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

“…( a ) Overall progression‐free survival (PFS) analysis for all four studies. Fang Combination Camrelizumab (Top L), Fang Monotherapy Camrelizumab (Top R), Ma Nivolumab (Bottom L), Hsu Pembrolizumab (Bottom R) . ( b ) Overall PFS based on the two studies with similar inclusion criteria and study characteristics.…”

“…( b ) Overall PFS based on the two studies with similar inclusion criteria and study characteristics. Pembrolizumab (KEYNOTE‐028) trial RED (bottom) line; Nivolumab trial (NCI‐9742) BLUE (middle) line (HLA expressing), YELLOW (top) line (loss of HLA‐A or HLA‐B). [Color figure can be viewed at wileyonlinelibrary.com]…”

“…Endemic NPC cases (WHO class 2/3) are associated with EBV and subsequently demonstrate a low tumour mutation burden . Given the information above, this observation may suggest a reason to be cautious regarding early anti‐PD1 clinical outcomes for the published NPC trials . Somewhat paradoxically, two recent studies, for HPV and polyomavirus associated cancers, respectively, report superior overall survival in patients undergoing anti‐PD1 treatment despite having low tumour mutation rates.…”

Epstein‐Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma: A nationwide study in Finland

“…Patients with EBV‐associated NPC are potential candidates for new immunotherapies. Indeed, recent clinical trials have studied therapeutic EBV vaccines and immune‐checkpoint inhibitors in patients with NPC with encouraging results for antitumor activity . EBV vaccines have mainly implied adoptive T‐cell therapy with EBV‐specific T cells prepared in vitro for infusion into patients.…”

Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma

“…Evidence for benefit of targeting the PD-1 pathway for patients with NPC has been demonstrated previously. 16,17 In the KEYNOTE-028 trial, twenty-seven patients with locally advanced, relapsed or metastatic, PD-L1 positive NPC were treated with pembrolizumab, and had an ORR of 26% (0CR, 7PR), DCR of 78%, and median PFS of 6.5 months. 16 …”