According to results of the KEYNOTE-122 (NCT02611960), multicentre, open-label, randomized phase III study, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., evaluating the efficacy and safety of pembrolizumab (Keytruda®) versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic nasopharyngeal carcinoma, shows that pembrolizumab did not prolong overall survival (OS) over chemotherapy in that population.[1]

The results of the study were presented by Prof. Anthony T.C. Chan, MD, the Li Shu Fan Professor of Clinical Oncology, Director of the Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute, Chief Director of Phase 1 Clinical Trial Centre, and Associate Dean (External Affairs) at the Chinese University of Hong Kong PRC, during the proffered papers session on head and neck cancer at ESMO Congress 2021, held online September 16-21, 2021.

Nasopharyngeal carcinoma, an Epstein–Barr virus (EBV)-associated cancer endemic to Southern China, Southeast Asia, and North Africa, is a type of head and neck cancer that starts in the nasopharynx, the upper part of the throat (pharynx), behind the nose and near the base of the skull. Although there have been many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma, there remains a major unmet medical need in treating patients diagnosed with the disease.

Limited treatment options
In his presentation during the 2021 annual meeting of the European Society for Medical Oncology, Professor Chan explained that treatment options for recurrent or metastatic nasopharyngeal carcinoma are limited. Previously, in the phase Ib KEYNOTE-028 study, pembrolizumab showed antitumor activity and manageable safety in a cohort of 27 patients with recurrent or metastatic nasopharyngeal carcinoma.

In the KEYNOTE-122, patients with histologically confirmed non-keratinizing differentiated (WHO Class II) or undifferentiated (WHO Class III), platinum-pretreated, Epstein-Barr virus-positive recurrent or metastatic nasopharyngeal carcinoma, with ECOG performance score 0-1, and measurable disease per RECIST v1.1 were randomized 1:1 to receive pembrolizumab every 3 weeks for up to 35 cycles or investigator’s choice of standard doses of chemotherapy.

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The study’s primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR), all measured per RECIST v1.1 by blinded independent central review.

Trial design
Between May 5, 2016, and May 28, 2018, 233 patients were randomized in this study, of whom 117 to pembrolizumab and 116 to chemotherapy. In the chemotherapy arm, 39 patients received capecitabine, 46 patients received gemcitabine and 31 patients received docetaxel. In the pembrolizumab arm 74.4% of patients and 62.9% of patients in the chemotherapy arm had PD-L1 combined positive score (CPS)≥1. The median time from the first dose to data cut-off performed on 30 November 2020) was 45.1 months (range, 30.2-54.8).

Professor Anthony T.C. Chan, MD, FRCP, FHKCP, FHKAof the Clinical Oncology Department, The Chinese University of Hong Kong, Hong Kong PRC 陳德章教授. Photo Courtesy: © 2016 – 2021. Department of Clinical Oncology. The Chinese University of Hong Kong. Used with permission.

In the intention-to-treat (ITT) population, median OS was 17.2 months (95% confidence interval [CI] 11.7–22.9) with pembrolizumab and 15.3 months (95% CI 10.9–18.1) with chemotherapy (hazard ratio 0.90; 95% CI 0.67-1.19; p = 0.2262; significance threshold for final analysis: 0.0187). In patients with PD-L1 CPS≥1, the OS was 17.2 months in pembrolizumab versus 18.0 months in the chemotherapy arm. The OS rate at 24 months was 40.2% with pembrolizumab compared to 32.2% with chemotherapy.

Median PFS was not different between the two arms, 4.1 months with pembrolizumab and 5.5 months with chemotherapy.

The ORR in the ITT population was 21.4% with pembrolizumab and 23.3% with chemotherapy, and 23.0% versus 26.0% in patients with PD-L1 CPS≥1. In ITT population, the disease control rate comprising the patients with complete and partial responses, as well as stable disease was 50.4% in patients who received pembrolizumab versus 63.8% in those who received chemotherapy.

The DoR was 12.0 months in patients treated with pembrolizumab versus 13.1 months in those treated with chemotherapy,

At the time of reporting, the biomarker analyses were ongoing.

Treatment-related adverse events rate was 61.2% in patients treated with pembrolizumab compared to 87.5% in those who received chemotherapy with grade 3-5 incidence of 10.3% in those treated with pembrolizumab versus 43.8% among patients who received chemotherapy.

Although in this study, pembrolizumab did not improve OS compared to chemotherapy in either the ITT or in patients with PD-L1 CPS ≥1, it did demonstrate manageable safety and a lower incidence of treatment-related adverse events.

Clinical Trials
Study of Pembrolizumab (MK-3475) in Platinum Pre-treated Recurrent/Metastatic Nasopharyngeal Cancer (MK-3475-122/KEYNOTE-122) – NCT02611960

Highlights of prescribing information
Pembrolizumab (Keytruda®; Merck & Co)[Prescribing Information]

Reference
[1] Chan ATC, Lee VHF, Hong R-L, et al. Results of KEYNOTE-122: A phase III study of pembrolizumab (pembro) monotherapy vs chemotherapy (chemo) for platinum-pretreated, recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Abstract 858O. Presented at the European Society for Medical Oncology (ESMO21), held September 16-21, 2021.

Featured image: ESMO 2015. Photo courtesy: © 2015 European Society for Medical Oncology/ESMO. Used with permission.

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