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Introduction <p>Based on the results of KEYNOTE-048 (NCT02358031), first-line standard-of-care treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) includes pembrolizumab alone or with platinum and fluorouracil (5-FU). Results from the single-arm KEYNOTE-B10 (NCT04489888) showed promising antitumor activity and a manageable safety profile offering an alternative pembrolizumab and chemotherapy regimen (KN-B10), with paclitaxel replacing 5-FU. With KEYNOTE-B10 being a non-comparative trial, this study aims to estimate the comparative efficacy of KN-B10 versus alternative first-line systemic treatments for R/M HNSCC via an indirect treatment comparison analysis.</p> Methods <p>A systematic literature review (October 2023) identified six connected randomized controlled trials with similar eligibility criteria to KEYNOTE-B10. Interventions included cetuximab + platinum + 5-FU (EXTREME), cetuximab + cisplatin + docetaxel (TPEx), pembrolizumab + platinum + 5-FU (KN-048), platinum + 5-FU, cisplatin + paclitaxel, cisplatin, 5-FU, and methotrexate. To connect KEYNOTE-B10 to the network, individual patient-level data were weighted to match the population characteristics of the most similar trial in the network (KEYNOTE-048). The comparative efficacy of KN-B10 versus other interventions was estimated via fixed-effect Bayesian network meta-analyses. Due to violations of the proportional-hazards assumption, fractional polynomials were used to model overall survival (OS) and progression-free survival (PFS).</p> Results <p>For objective response, KN-B10 was comparable to EXTREME and TPEx and more efficacious than all other identified treatments (range of odds ratios [ORs]: 1.69–11.75), including KN-048 (OR: 1.69; 95% credible interval: 1.01–2.81). For OS and PFS, KN-B10 was comparable to EXTREME (with improvements in OS after month 12), TPEx, and KN-048. KN-B10 improved OS versus platinum + 5-FU (range of time-varying hazard ratios: 0.60–0.18; months 9–60), cisplatin + paclitaxel (0.53–0.24; 9–36), cisplatin (0.59–0.32; 6–24), 5-FU (0.58–0.20; 6–36), and methotrexate (0.61–0.07; 6–60). KN-B10 improved PFS versus platinum + 5-FU (0.60–0.31; 3–36).</p> Conclusion <p>The improved&#xa0;or comparable efficacy of KN-B10 versus alternative first-line interventions in terms of relevant clinical outcomes, as shown in this study, supports its recommendations for the treatment of R/M HNSCC.</p>

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Pembrolizumab with Carboplatin and Paclitaxel Versus Alternative Systemic Treatments Recommended for the First-Line Treatment of Recurrent/Metastatic Head and Neck Cancer: An Indirect Treatment Comparison

  • 期刊论文

  • 发表日期：

    2025年4月24日

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  • Marcin Dzienis,
  • Ali Mojebi,
  • Sam Keeping,
  • Christopher M. Black,
  • Hilde Giezek,
  • Niroshini Naicker,
  • Chiara Vanetta,
  • Julie E. Park,
  • Keith Chan,
  • Sanjay Merchant,
  • Dandan Zheng

摘要

Introduction

Based on the results of KEYNOTE-048 (NCT02358031), first-line standard-of-care treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) includes pembrolizumab alone or with platinum and fluorouracil (5-FU). Results from the single-arm KEYNOTE-B10 (NCT04489888) showed promising antitumor activity and a manageable safety profile offering an alternative pembrolizumab and chemotherapy regimen (KN-B10), with paclitaxel replacing 5-FU. With KEYNOTE-B10 being a non-comparative trial, this study aims to estimate the comparative efficacy of KN-B10 versus alternative first-line systemic treatments for R/M HNSCC via an indirect treatment comparison analysis.

Methods

A systematic literature review (October 2023) identified six connected randomized controlled trials with similar eligibility criteria to KEYNOTE-B10. Interventions included cetuximab + platinum + 5-FU (EXTREME), cetuximab + cisplatin + docetaxel (TPEx), pembrolizumab + platinum + 5-FU (KN-048), platinum + 5-FU, cisplatin + paclitaxel, cisplatin, 5-FU, and methotrexate. To connect KEYNOTE-B10 to the network, individual patient-level data were weighted to match the population characteristics of the most similar trial in the network (KEYNOTE-048). The comparative efficacy of KN-B10 versus other interventions was estimated via fixed-effect Bayesian network meta-analyses. Due to violations of the proportional-hazards assumption, fractional polynomials were used to model overall survival (OS) and progression-free survival (PFS).

Results

For objective response, KN-B10 was comparable to EXTREME and TPEx and more efficacious than all other identified treatments (range of odds ratios [ORs]: 1.69–11.75), including KN-048 (OR: 1.69; 95% credible interval: 1.01–2.81). For OS and PFS, KN-B10 was comparable to EXTREME (with improvements in OS after month 12), TPEx, and KN-048. KN-B10 improved OS versus platinum + 5-FU (range of time-varying hazard ratios: 0.60–0.18; months 9–60), cisplatin + paclitaxel (0.53–0.24; 9–36), cisplatin (0.59–0.32; 6–24), 5-FU (0.58–0.20; 6–36), and methotrexate (0.61–0.07; 6–60). KN-B10 improved PFS versus platinum + 5-FU (0.60–0.31; 3–36).

Conclusion

The improved or comparable efficacy of KN-B10 versus alternative first-line interventions in terms of relevant clinical outcomes, as shown in this study, supports its recommendations for the treatment of R/M HNSCC.