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 We report the updated results.Published or unpublished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.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).The update of MACH-NC confirms the benefit and superiority of the
addition of concomitant CT for non-metastatic head and neck cancer.
