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

Lacas, B.; Carmel, A.; Landais, C.; Wong, S. J.; Licitra, L.; Tobias, J. S.; Burtness, B.; Ghi, M. G.; Cohen, E. E. W.; Grau, C.; Wolf, G.; Hitt, R.; Corvo, R.; Budach, V.; Kumar, S.; Laskar, S. G.; Mazeron, J. -J.; Zhong, L. -P.; Dobrowsky, W.; Ghadjar, P.; Fallai, C.; Zakotnik, B.; Sharma, A.; Bensadoun, R. -J.; Ruo Redda, M. G.; Racadot, S.; Fountzilas, G.; Brizel, D.; Rovea, P.; Argiris, A.; Nagy, Z. T.; Lee, J. -W.; Fortpied, C.; Harris, J.; Bourhis, J.; Auperin, A.; Blanchard, P.; Pignon, J. -P.; Adelstein, D. J.; Alfonsi, M.; Belkacemi, Y.; Bar-Ad, V.; Bernier, J.; Bratland, A.; Calais, G.; Campbell, B.; Caudell, J.; Chabaud, S.; Chamorey, E.; Chaukar, D.; Choi, K. N.; Choussy, O.; Collette, L.; Cruz, J. J.; Dani, C.; Dauzier, E.; Forastiere, A. A.; Garaud, P.; Gregoire, V.; Hackshaw, A.; Haddad, E.; Haffty, B. G.; Hansen, A.; Hayoz, S.; Horiot, J. C.; Jeremic, B.; Karrison, T. G.; Langendijk, J. A.; Lapeyre, M.; Lartigau, E.; Leong, T.; Q. T., Le; Lee, P. P. Y.; Lewin, F.; Lin, A.; Lopes, A.; Mehta, S.; Moon, J.; Moyal, E.; Occean, B. V.; Olmi, P.; Orecchia, R.; O'Sullivan, B.; Overgaard, J.; Petit, C.; Quon, H.; Sanguineti, G.; Satar, T.; Simes, J.; Simon, C.; Sire, C.; Staar, S.; Stromberger, C.; Strojan, P.; Temam, S.; Thomson, D.; Timochenko, A.; Torri, V.; Tseroni, V.; Vermorken, J.; Vokes, E. E.; Waldron, J.; Wernecke, K. D.; Widder, J.; Zackrisson, B.

doi:10.1016/j.radonc.2021.01.013

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 Materials and methods: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT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.