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. (March 2021)

• Record Type: Journal Article
• Authors: Lacas, Benjamin; Carmel, Alexandra; Landais, Cécile; Wong, Stuart J.; Licitra, Lisa; Tobias, Jeffrey S.; Burtness, Barbara; Ghi, Maria Grazia; Cohen, Ezra E.W.; Grau, Cai; Wolf, Gregory; Hitt, Ricardo; Corvò, Renzo; Budach, Volker; Kumar, Shaleen; Laskar, Sarbani Ghosh; Mazeron, Jean-Jacques; Zhong, Lai-Ping; Dobrowsky, Werner; Ghadjar, Pirus; Fallai, Carlo; Zakotnik, Branko; Sharma, Atul; Bensadoun, René-Jean; Ruo Redda, Maria Grazia; Racadot, Séverine; Fountzilas, George; Brizel, David; Rovea, Paolo; Argiris, Athanassios; Nagy, Zoltán Takácsi; Lee, Ju-Whei; Fortpied, Catherine; Harris, Jonathan; Bourhis, Jean; Aupérin, Anne; Blanchard, Pierre; Pignon, Jean-Pierre; Adelstein, D.J.; Alfonsi, M.; Belkacemi, Y.; Bar-Ad, V.; Bernier, J.; Bratland, Å.; 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.; Le, Q.T.; Lee, P.P.Y.; Lewin, F.; Lin, A.; Lopes, A.; Mehta, S.; Moon, J.; Moyal, E.; Occéan, 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.;
• Is Part Of: Radiotherapy and oncology. Volume 156(2021)
• Page Start: 281
• Page End: 293
• Publication Date: 2021-03
• Subjects: Meta-analysis -- Individual Patient Data -- Randomised Clinical Trials -- Chemotherapy -- Radiotherapy -- Head and Neck Cancer; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2021.01.013
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: MACH-NC second update with 107 randomized trials (19805 patients) investigating chemotherapy (CT) in non-metastatic HNSCC. Overall Survival (OS) improved by CT, benefit superior for concomitant CT (HR 0.83 [0.79; 0.86]) over induction or adjuvant CT. Direct comparison confirmed the superiority of concomitant over induction CT on OS. 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.