Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

Benjamin Lacas; Alexandra Carmel; Cécile Landais; Stuart J Wong; Lisa Licitra; Jeffrey S Tobias; Barbara Burtness; Maria Grazia Ghi; Ezra E W Cohen; Cai Grau; Gregory Wolf; Ricardo Hitt; Renzo Corvò; Volker Budach; Shaleen Kumar; Sarbani Ghosh Laskar; Jean-Jacques Mazeron; Lai-Ping Zhong; Werner Dobrowsky; Pirus Ghadjar; Carlo Fallai; Branko Zakotnik; Atul Sharma; René-Jean Bensadoun; Maria Grazia Ruo Redda; Séverine Racadot; George Fountzilas; David Brizel; Paolo Rovea; Athanassios Argiris; Zoltán Takácsi Nagy; Ju-Whei Lee; Catherine Fortpied; Jonathan Harris; Jean Bourhis; Anne Aupérin; Pierre Blanchard; Jean-Pierre Pignon; MACH-NC Collaborative Group

doi:10.1016/j.radonc.2021.01.013

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

Radiother Oncol. 2021 Mar:156:281-293. doi: 10.1016/j.radonc.2021.01.013. Epub 2021 Jan 27.

Authors

Benjamin Lacas¹, Alexandra Carmel², Cécile Landais², Stuart J Wong³, Lisa Licitra⁴, Jeffrey S Tobias⁵, Barbara Burtness⁶, Maria Grazia Ghi⁷, Ezra E W Cohen⁸, Cai Grau⁹, Gregory Wolf¹⁰, Ricardo Hitt¹¹, Renzo Corvò¹², Volker Budach¹³, Shaleen Kumar¹⁴, Sarbani Ghosh Laskar¹⁵, Jean-Jacques Mazeron¹⁶, Lai-Ping Zhong¹⁷, Werner Dobrowsky¹⁸, Pirus Ghadjar¹⁹, Carlo Fallai⁷, Branko Zakotnik¹⁰, Atul Sharma²⁰, René-Jean Bensadoun²¹, Maria Grazia Ruo Redda²², Séverine Racadot²³, George Fountzilas²⁴, David Brizel²⁵, Paolo Rovea²⁶, Athanassios Argiris²⁷, Zoltán Takácsi Nagy²⁸, Ju-Whei Lee²⁹, Catherine Fortpied³⁰, Jonathan Harris³¹, Jean Bourhis³², Anne Aupérin¹, Pierre Blanchard³³, Jean-Pierre Pignon¹; MACH-NC Collaborative Group

Collaborators

MACH-NC Collaborative Group:
D J Adelstein³⁴, M Alfonsi³⁵, Y Belkacemi³⁶, V Bar-Ad³⁷, J Bernier³⁸, Å Bratland³⁹, G Calais⁴⁰, B Campbell⁴¹, J Caudell⁴², S Chabaud⁴³, E Chamorey⁴⁴, D Chaukar⁴⁵, K N Choi⁴⁶, O Choussy⁴⁷, L Collette⁴⁸, J J Cruz⁴⁹, C Dani⁵⁰, E Dauzier⁵¹, A A Forastiere⁵², P Garaud⁵³, V Gregoire⁵⁴, A Hackshaw⁵⁵, E Haddad⁵⁶, B G Haffty⁵⁷, A Hansen⁵⁸, S Hayoz⁵⁹, J C Horiot⁶⁰, B Jeremic⁶¹, T G Karrison⁶², J A Langendijk⁶³, M Lapeyre⁶⁴, E Lartigau⁶⁵, T Leong⁶⁶, Q T Le⁶⁷, P P Y Lee⁶⁸, F Lewin⁶⁹, A Lin⁷⁰, A Lopes²⁰, S Mehta⁷¹, J Moon⁷², E Moyal⁷³, B V Occéan¹⁸, P Olmi⁷⁴, R Orecchia⁷⁵, B O'Sullivan²³, J Overgaard⁷⁶, C Petit¹⁸, H Quon¹⁹, G Sanguineti⁷⁷, T Satar¹⁸, J Simes⁷⁸, C Simon⁷⁹, C Sire⁸⁰, S Staar⁸¹, C Stromberger⁸², P Strojan⁸³, S Temam¹⁸, D Thomson⁸⁴, A Timochenko⁸⁵, V Torri⁸⁶, V Tseroni⁸⁷, J Vermorken⁸⁸, E E Vokes⁸⁹, J Waldron²³, K D Wernecke⁸², J Widder⁹⁰, B Zackrisson⁹¹

Affiliations

¹ Cleveland Clinic Foundation, OH, USA; Institut Saint Catherine, France.
² Cleveland Clinic Foundation, OH, USA.
³ CHU Henri Mondor, France.
⁴ Thomas Jefferson University Hospital, USA.
⁵ Genolier Swiss Oncology Network, Switzerland.
⁶ Oslo University Hospital, Norway.
⁷ Centre Hospitalier Universitaire de Tours, France.
⁸ Medical College of Wisconsin, USA.
⁹ H. Lee Moffitt Cancer Center & Research Institute, USA.
¹⁰ Centre Léon Bérard, France.
¹¹ Centre Antoine Lacassagne, France.
¹² Tata Memorial Centre Advanced Centre for Treatment, Research and Education in Cancer, India.
¹³ State University of New York Downstate Medical Center, USA.
¹⁴ Institut Curie, France.
¹⁵ EORTC Headquarters, Belgium.
¹⁶ Spanish Head and Neck Cancer Cooperative Group, Spain.
¹⁷ Ospedale Policlinico San Martino, Genoa, Italy.
¹⁸ Gustave Roussy, France.
¹⁹ Johns Hopkins Univ/Sidney Kimmel Cancer Center, MD, USA.
²⁰ Cancer Research UK & UCL Cancer Trials Centre, UK.
²¹ Hôpital Henri Mondor, Créteil, France.
²² Rutgers Robert Wood Johnson and NJ Medical School, NJ, USA.
²³ Princess Margaret Cancer Centre/University of Toronto, Ontario, Canada.
²⁴ SAKK Coordinating Center, Switzerland.
²⁵ Centre Georges François Leclerc, France.
²⁶ Kragulevac University Hospital, Yugoslavia, Serbia.
²⁷ University of Chicago, IL, USA.
²⁸ University Medical Center Groningen, Netherlands.
²⁹ Centre Jean Perrin, France.
³⁰ Centre Oscar Lambret, France.
³¹ Rollins School of Public Health, Emory University, GA, USA.
³² Institut Saint Catherine, France; Stanford University School of Medicine, CA, USA.
³³ Cleveland Clinic Foundation, OH, USA; Institut Saint Catherine, France; University of Texas-MD Anderson Cancer Center, USA. Electronic address: [email protected].
³⁴ Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France.
³⁵ Groupe d'Oncologie Radiothérapie Tête Et Cou, Tours, France.
³⁶ Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
³⁷ Department of Medical Oncology 3, Fondazione IRCCS-Istituto Nazionale dei Tumori, Milano and University of Milan, Italy.
³⁸ Department of Radiotherapy, University College London Hospital, UK.
³⁹ Department of Internal Medicine and Yale Cancer Center, Yale University, New Haven, USA.
⁴⁰ Oncology Unit 2, Veneto Oncology Institute-IRCCS, Padua, Italy.
⁴¹ UC San Diego, Moores Cancer Center, California, USA.
⁴² Department of Experimental Clinical Oncology, Aarhus, Denmark.
⁴³ Department of Otolaryngology, University of Michigan, Ann Arbor, USA.
⁴⁴ Servicio Oncologia Medica, Hospital Universitario Severo Ochoa, Madrid, Spain.
⁴⁵ Department of Radiation Oncology, Ospedale Policlinico San Martino and University of Genoa, Genoa, Italy.
⁴⁶ Department of Radiation Oncology, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁴⁷ Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
⁴⁸ Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute Mumbai, India.
⁴⁹ Département de radiothérapie, hôpital Pitié-Salpêtrière, Paris, France.
⁵⁰ Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵¹ Dept. Clinical Oncology, Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
⁵² Department of Radiation Oncology, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany and SAKK Coordinating Center, Bern, Switzerland.
⁵³ Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
⁵⁴ Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia.
⁵⁵ Departments of Medical Oncology, Dr BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
⁵⁶ Departments of Radiation Oncology, Centre Antoine Lacassagne, Nice, France.
⁵⁷ Department of Radiation Oncology, Mauriziano Umberto I Hospital, University of Turin School of Medicine, Turin, Italy.
⁵⁸ Department of Radiation Oncology, Centre Léon Bérard, Lyon, France.
⁵⁹ Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
⁶⁰ Departments of Radiation Oncology, Duke University Medical Center, Durham, USA.
⁶¹ Radiation Oncology Unit, San Giovanni Antica Sede Hospital, Turin, Italy.
⁶² Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, USA.
⁶³ Center of Radiotherapy, National Institute of Oncology, Department of Oncology, Semmelweis University, Budapest, Hungary.
⁶⁴ Dana Farber Cancer Institute - ECOG-ACRIN Biostatistics Center, Boston, USA.
⁶⁵ EORTC Headquarters, Brussels, Belgium.
⁶⁶ NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, USA.
⁶⁷ Department of Radiotherapy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁶⁸ Department of Radiation Therapy, Gustave Roussy Cancer Campus, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
⁶⁹ Huddinge University Hospital, Sweden.
⁷⁰ University of Pennsylvania Medical Center, USA.
⁷¹ Department of Surgery, Sarla Hospital, India.
⁷² SWOG Statistical Center, WA, USA.
⁷³ IUCT Oncopole - CLCC Institut Claudius Regaud, France.
⁷⁴ Università di Firenze, Italy.
⁷⁵ IRCCS Istituto Europeo di Oncologia, Italy.
⁷⁶ Aarhus University Hospital, Denmark.
⁷⁷ IRCCS Regina Elena National Cancer Institute, Rome, Italy.
⁷⁸ NHMRC Clinical Trials Center, Australia.
⁷⁹ Centre Hospitalier Universitaire Vaudois, Switzerland.
⁸⁰ Hôpital Bretagne Sud, France.
⁸¹ University of Cologne, Germany.
⁸² Charité Universitätsmedizin, Germany.
⁸³ Institute of Oncology, Slovenia.
⁸⁴ The Christie NHS FT, UK.
⁸⁵ CHU de St-Etienne, France.
⁸⁶ Mario Negri, Italy.
⁸⁷ San Giovanni Antica Sede Hospital, Italy.
⁸⁸ Antwerp University Hospital, Belgium.
⁸⁹ University of Chicago Medical Center, IL, USA.
⁹⁰ Medical University of Vienna, Austria.
⁹¹ Umeå University, Sweden.

Abstract

Background and purpose: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.

Materials and methods: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint.

Results: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005).

Conclusion: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.

Keywords: Chemotherapy; Head and Neck Cancer; Individual Patient Data; Meta-analysis; Radiotherapy; Randomised Clinical Trials.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Squamous Cell* / drug therapy
Chemotherapy, Adjuvant
Head and Neck Neoplasms* / therapy
Humans
Induction Chemotherapy
Randomized Controlled Trials as Topic

Abstract

Publication types

MeSH terms

Grants and funding