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, D J Adelstein, M Alfonsi, Y Belkacemi, V Bar-Ad, J Bernier, Å Bratland, G Calais, B Campbell, J Caudell, S Chabaud, E Chamorey, D Chaukar, K N Choi, O Choussy, L Collette, J J Cruz, C Dani, E Dauzier, A A Forastiere, P Garaud, V Gregoire, A Hackshaw, E Haddad, B G Haffty, A Hansen, S Hayoz, J C Horiot, B Jeremic, T G Karrison, J A Langendijk, M Lapeyre, E Lartigau, T Leong, Q T Le, P P Y Lee, F Lewin, A Lin, A Lopes, S Mehta, J Moon, E Moyal, B V Occéan, P Olmi, R Orecchia, B O'Sullivan, J Overgaard, C Petit, H Quon, G Sanguineti, T Satar, J Simes, C Simon, C Sire, S Staar, C Stromberger, P Strojan, S Temam, D Thomson, A Timochenko, V Torri, V Tseroni, J Vermorken, E E Vokes, J Waldron, K D Wernecke, J Widder, B Zackrisson, 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, D J Adelstein, M Alfonsi, Y Belkacemi, V Bar-Ad, J Bernier, Å Bratland, G Calais, B Campbell, J Caudell, S Chabaud, E Chamorey, D Chaukar, K N Choi, O Choussy, L Collette, J J Cruz, C Dani, E Dauzier, A A Forastiere, P Garaud, V Gregoire, A Hackshaw, E Haddad, B G Haffty, A Hansen, S Hayoz, J C Horiot, B Jeremic, T G Karrison, J A Langendijk, M Lapeyre, E Lartigau, T Leong, Q T Le, P P Y Lee, F Lewin, A Lin, A Lopes, S Mehta, J Moon, E Moyal, B V Occéan, P Olmi, R Orecchia, B O'Sullivan, J Overgaard, C Petit, H Quon, G Sanguineti, T Satar, J Simes, C Simon, C Sire, S Staar, C Stromberger, P Strojan, S Temam, D Thomson, A Timochenko, V Torri, V Tseroni, J Vermorken, E E Vokes, J Waldron, K D Wernecke, J Widder, B Zackrisson
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.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Copyright © 2021 Elsevier B.V. All rights reserved.
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Source: PubMed