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
- Study type
- Meta-analysis
- Study name
- MACH-NC
- Design
- Individual patient data (IPD) meta-analysis of published and unpublished randomised trials (1965 to 2016); fixed-effect model
- Sample size
- 107 trials; 19,805 patients
- Source
- Radiother Oncol · 2021
In plain words
This is the largest combined analysis of head and neck cancer trials (nearly 20 thousand patients). The main result: giving chemotherapy at the same time as radiotherapy increases the chance of being alive after 5 years by about 6.5 percentage points, but chemotherapy given before or after radiotherapy generally has no such effect. The benefit is smaller in older patients.
Key results
Treatment arms and regimens
Definitive locoregional treatment (surgery and/or radiotherapy) versus the same treatment with chemotherapy, or adding another chemotherapy timing to locoregional treatment with chemotherapy. Comparisons by chemotherapy timing:
- Concurrent (71 comparisons, 10,680 patients): single-agent or multi-agent, with or without a platinum salt.
- Induction (45 comparisons, 7054 patients): TPF (taxane + platinum + 5-FU), PF (platinum + 5-FU) and other regimens.
- Adjuvant (14 comparisons, 2915 patients).
Drugs and doses varied between trials and there is no single dose; comparison of weekly versus 3-weekly cisplatin was outside the scope of this meta-analysis.
Eight comparisons (1214 patients) with the same drugs in both groups, comparing only the timing: induction chemotherapy followed by radiotherapy versus radiotherapy with concurrent (or alternating) chemotherapy.
Source of the regimen details: Full text of the paper (PMC8386522); meta-analysis — regimens varied, with no single dose
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with non-metastatic squamous cell carcinoma of the head and neck (about 90% stage III or IV).
Endpoints
Primary endpoint: overall survival.
Safety and side effects
Acute and late toxicity were collected but not analysed in this report. 120-day mortality (an indicator of treatment-related death): concurrent chemotherapy HR 1.07 (95% CI 0.92–1.24; not significant), induction HR 1.07 (0.89–1.28; not significant) and adjuvant HR 1.89 (1.33–2.68; p=0.0003; significant increase). Excess early deaths were seen in two TPF trials that had not selected patients appropriately or had not used G-CSF. The benefit of concurrent chemotherapy decreased with age, and the authors recommended that its use after age 70 be carefully weighed.
Clinical significance and place in guidelines
MACH-NC is the main evidence base for concurrent chemoradiotherapy (usually with cisplatin) as the standard non-surgical treatment of locally advanced head and neck cancer, and it explains why induction chemotherapy is not routinely recommended except for larynx preservation (and in nasopharyngeal carcinoma, which is a different disease).
Limitations
Many of the trials are old and were conducted before the era of IMRT, HPV testing and current regimens (such as TPF); heterogeneity of chemotherapy and radiotherapy regimens is high.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.