Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)

Sara I. Pai, Sandrine Faivre, Lisa Licitra, Jean Pascal Machiels, Jan B. Vermorken, Paolo Bruzzi, Viktor Gruenwald, Raul E. Giglio, C. René Leemans, Tanguy Lim Seiwert, Denis Soulieres

Research output: Contribution to journalReview article

Abstract

Two phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51-0.96; p = 0.01) and HR of 0.80 (95%CI 0.65-0.98, p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or methotrexate). The gain in OS was similar in both studies, underscoring the role of anti-PD1 drugs in R/M HNSCC patients. One of the striking discrepancies between CheckMate 141 and KEYNOTE 040 was the OS observed in the control SOC arms (6.9 months median in KEYNOTE 040 versus 5.1 months in CheckMate 141), which inadvertently set a higher threshold in the bio-statistical analysis of KEYNOTE 040 so that the clinical outcome of every patient was influential in the analysis. We perform a comparative analysis of the two studies to identify potential factors in the control arm that can impact clinical trial bio-statistical outcomes and which may have implications for future immunotherapy clinical trial designs.

Original languageEnglish (US)
Article number96
JournalJournal for immunotherapy of cancer
Volume7
Issue number1
DOIs
StatePublished - Apr 3 2019
Externally publishedYes

Fingerprint

Phase III Clinical Trials
Survival
docetaxel
Standard of Care
Clinical Trials
Platinum
Methotrexate
Immunotherapy
Carcinoma, squamous cell of head and neck
Therapeutics
Pharmaceutical Preparations

Keywords

  • Anti-PD-1 therapy
  • Clinical trials
  • Head and neck squamous cell carcinoma
  • Immune checkpoint therapy
  • Immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). / Pai, Sara I.; Faivre, Sandrine; Licitra, Lisa; Machiels, Jean Pascal; Vermorken, Jan B.; Bruzzi, Paolo; Gruenwald, Viktor; Giglio, Raul E.; Leemans, C. René; Lim Seiwert, Tanguy; Soulieres, Denis.

In: Journal for immunotherapy of cancer, Vol. 7, No. 1, 96, 03.04.2019.

Research output: Contribution to journalReview article

Pai, Sara I. ; Faivre, Sandrine ; Licitra, Lisa ; Machiels, Jean Pascal ; Vermorken, Jan B. ; Bruzzi, Paolo ; Gruenwald, Viktor ; Giglio, Raul E. ; Leemans, C. René ; Lim Seiwert, Tanguy ; Soulieres, Denis. / Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). In: Journal for immunotherapy of cancer. 2019 ; Vol. 7, No. 1.
@article{d7d5fc230ee64a19ae0ecca6d88f875f,
title = "Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)",
abstract = "Two phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95{\%}CI 0.51-0.96; p = 0.01) and HR of 0.80 (95{\%}CI 0.65-0.98, p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or methotrexate). The gain in OS was similar in both studies, underscoring the role of anti-PD1 drugs in R/M HNSCC patients. One of the striking discrepancies between CheckMate 141 and KEYNOTE 040 was the OS observed in the control SOC arms (6.9 months median in KEYNOTE 040 versus 5.1 months in CheckMate 141), which inadvertently set a higher threshold in the bio-statistical analysis of KEYNOTE 040 so that the clinical outcome of every patient was influential in the analysis. We perform a comparative analysis of the two studies to identify potential factors in the control arm that can impact clinical trial bio-statistical outcomes and which may have implications for future immunotherapy clinical trial designs.",
keywords = "Anti-PD-1 therapy, Clinical trials, Head and neck squamous cell carcinoma, Immune checkpoint therapy, Immunotherapy",
author = "Pai, {Sara I.} and Sandrine Faivre and Lisa Licitra and Machiels, {Jean Pascal} and Vermorken, {Jan B.} and Paolo Bruzzi and Viktor Gruenwald and Giglio, {Raul E.} and Leemans, {C. Ren{\'e}} and {Lim Seiwert}, Tanguy and Denis Soulieres",
year = "2019",
month = "4",
day = "3",
doi = "10.1186/s40425-019-0578-0",
language = "English (US)",
volume = "7",
journal = "Journal for ImmunoTherapy of Cancer",
issn = "2051-1426",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)

AU - Pai, Sara I.

AU - Faivre, Sandrine

AU - Licitra, Lisa

AU - Machiels, Jean Pascal

AU - Vermorken, Jan B.

AU - Bruzzi, Paolo

AU - Gruenwald, Viktor

AU - Giglio, Raul E.

AU - Leemans, C. René

AU - Lim Seiwert, Tanguy

AU - Soulieres, Denis

PY - 2019/4/3

Y1 - 2019/4/3

N2 - Two phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51-0.96; p = 0.01) and HR of 0.80 (95%CI 0.65-0.98, p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or methotrexate). The gain in OS was similar in both studies, underscoring the role of anti-PD1 drugs in R/M HNSCC patients. One of the striking discrepancies between CheckMate 141 and KEYNOTE 040 was the OS observed in the control SOC arms (6.9 months median in KEYNOTE 040 versus 5.1 months in CheckMate 141), which inadvertently set a higher threshold in the bio-statistical analysis of KEYNOTE 040 so that the clinical outcome of every patient was influential in the analysis. We perform a comparative analysis of the two studies to identify potential factors in the control arm that can impact clinical trial bio-statistical outcomes and which may have implications for future immunotherapy clinical trial designs.

AB - Two phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51-0.96; p = 0.01) and HR of 0.80 (95%CI 0.65-0.98, p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or methotrexate). The gain in OS was similar in both studies, underscoring the role of anti-PD1 drugs in R/M HNSCC patients. One of the striking discrepancies between CheckMate 141 and KEYNOTE 040 was the OS observed in the control SOC arms (6.9 months median in KEYNOTE 040 versus 5.1 months in CheckMate 141), which inadvertently set a higher threshold in the bio-statistical analysis of KEYNOTE 040 so that the clinical outcome of every patient was influential in the analysis. We perform a comparative analysis of the two studies to identify potential factors in the control arm that can impact clinical trial bio-statistical outcomes and which may have implications for future immunotherapy clinical trial designs.

KW - Anti-PD-1 therapy

KW - Clinical trials

KW - Head and neck squamous cell carcinoma

KW - Immune checkpoint therapy

KW - Immunotherapy

UR - http://www.scopus.com/inward/record.url?scp=85063941698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063941698&partnerID=8YFLogxK

U2 - 10.1186/s40425-019-0578-0

DO - 10.1186/s40425-019-0578-0

M3 - Review article

C2 - 30944020

AN - SCOPUS:85063941698

VL - 7

JO - Journal for ImmunoTherapy of Cancer

JF - Journal for ImmunoTherapy of Cancer

SN - 2051-1426

IS - 1

M1 - 96

ER -