Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial

Chan ATC 1 , Lee VHF 2 , Hong RL 3 , Ahn MJ 4 , Chong WQ 5 , Kim SB 6 Show all authors , Ho GF 7 , Caguioa PB 8 , Ngamphaiboon N 9 , Ho C 10 , Aziz MASA 11 , Ng QS 12 , Yen CJ 13 , Soparattanapaisarn N 14 , Ngan RK 15 , Kho SK 16 , Tiambeng MLA 17 , Yun T 18 , Sriuranpong V 19 , Algazi AP 20 , Cheng A 21 , Massarelli E 22 , Swaby RF 23 , Saraf S 23 , Yuan J 23 , Siu LL 24

Affiliations 

  • 1 State Key Laboratory in Translational Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: anthonytcchan@cuhk.edu.hk
  • 2 Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China
  • 3 National Taiwan University Hospital, Taipei, Taiwan
  • 4 Samsung Medical Centre, Seoul, South Korea
  • 5 National University Cancer Institute, Singapore, Singapore
  • 6 Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea
  • 7 Clinical Oncology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 8 St. Luke's Medical Center, University of Santo Tomas Faculty of Medicine and Surgery, Manila, Philippines
  • 9 Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • 10 BC Cancer, University of British Columbia, Vancouver, Canada
  • 11 Gleneagles Penang Clinical Research Center, Gleneagles Hospital Penang, Penang, Malaysia
  • 12 National Cancer Centre Singapore, Singapore, Singapore
  • 13 National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • 14 Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 15 Queen Elizabeth Hospital, Kowloon, Hong Kong, China
  • 16 Hospital Umum Sarawak, Kuching, Malaysia
  • 17 Cardinal Santos Medical Center, San Juan City, Philippines
  • 18 National Cancer Center, Goyang-si, South Korea
  • 19 Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  • 20 UCSF, San Francisco, USA
  • 21 Princess Margaret Hospital, Hong Kong, China
  • 22 City of Hope Comprehensive Cancer Center, Duarte, USA
  • 23 Merck & Co., Inc., Rahway, USA
  • 24 Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
Ann Oncol, 2023 Mar;34(3):251-261.
PMID: 36535566 DOI: 10.1016/j.annonc.2022.12.007

Abstract

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented.

PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population.

RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage).

CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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