According to results of the KEYNOTE-122, multicentre, open-label, randomised phase III study that evaluated the efficacy and safety of pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic nasopharyngeal carcinoma, pembrolizumab did not prolong overall survival (OS) over chemotherapy in that population. The results were presented by Prof. Anthony T.C. Chan of the Clinical Oncology Department, The Chinese University of Hong Kong, Hong Kong PRC during the proffered papers session on head and neck cancer at ESMO Congress 2021 (16-21 September).
Prof. Chan explained that treatment options for recurrent or metastatic nasopharyngeal carcinoma are limited. Previously, in the phase Ib KEYNOTE-028 study, pembrolizumab showed antitumour 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-keratinising 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 randomised 1:1 to receive pembrolizumab every 3 weeks for up to 35 cycles or investigator’s choice of standard doses of chemotherapy.
The study primary endpoint was OS. 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.
Between 5 May 2016 and 28 May 2018, 233 patients were randomised in this study, of whom 117 to pembrolizumab and 116 to chemotherapy. In chemotherapy arm, 39 patients received capecitabine, 46 patients received gemcitabine and 31 patients received docetaxel. In the pembrolizumab arm 74.4% patients and 62.9% patients in the chemotherapy arm had PD-L1 combined positive score (CPS)≥1. Median time from the first dose to data cut-off performed on 30 November 2020) was 45.1 months (range, 30.2-54.8).
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 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 two arms, 4.1 month with pembrolizumab and 5.5. month 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, disease control rate comprising the patients with complete and partial responses, as well with a 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, neither in ITT or in patients with PD-L1 CPS ≥1, it showed manageable safety and a lower incidence of treatment-related adverse events.
The study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
858O – 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). ESMO Congress 2021 (16-21 September).