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MACH-NC

Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC): individual patient data meta-analyses of randomised trials of chemotherapy added to locoregional treatment

Phase meta-analysis

Population
Patients with non-metastatic head and neck squamous cell carcinoma in randomised trials of locoregional treatment with or without chemotherapy; about 90% had stage III or IV disease in the 2021 update
Design
Individual-patient-data meta-analyses by the MACH-NC group. 2000 report: randomised trials 1965 to 1993; 2009 update: trials 1965 to 2000; 2021 update: trials randomised 1965 to 2016. Oropharynx, oral cavity, larynx and hypopharynx carcinoma (2000 report); non-metastatic head and neck cancer (later updates). The 2021 update used a fixed-effect model and OS as the main endpoint.
Primary endpoint
OS
Arms
  • Locoregional treatment alone (control): Surgery and/or radiotherapy without chemotherapy
  • Locoregional treatment plus chemotherapy (experimental): Same locoregional treatment plus chemotherapy (adjuvant, induction or concomitant)
People
Pignon JP, MACH-NC Collaborative Group
OSHR 0.90 (95% CI 0.85–0.94)OSHR 1.19 (95% CI 0.97–1.46)OSHR 0.81OSHR 0.83 (95% CI 0.79–0.86)OSHR 0.96 (95% CI 0.90–1.01)OSHR 1.02 (95% CI 0.92–1.13)
Show the numbers
Results reported for MACH-NC
EndpointAnalysisLocoregional treatment plus chemotherapyLocoregional treatment aloneEffect
OS63 trials of locoregional treatment with or without chemotherapy (10,741 patients)primaryPignon 2000——HR 0.90 (95% CI 0.85–0.94)P<0.000163 trials, 10,741 patients; absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. No significant benefit with adjuvant or neoadjuvant chemotherapy; concomitant chemotherapy gave significant benefits, but heterogeneity prohibited firm conclusions (abstract).
OSThree larynx-preservation trials (602 patients): radical surgery plus radiotherapy versus neoadjuvant chemotherapy plus radiotherapy in responders (radical surgery and radiotherapy in non-responders)primaryPignon 2000——HR 1.19 (95% CI 0.97–1.46)Non-significant; the authors concluded that the organ-preservation procedure 'must remain investigational'.
OS50 trials of concomitant chemotherapylong term-updatePignon 2009——HR 0.81P<0.0001Absolute benefit 6.5% at 5 years. All 87 trials (16,485 patients) in the abstract: HR of death 0.88 (p<0.0001), absolute benefit 4.5% at 5 years. The paper's title cites 93 trials and 17,346 patients, which differs from the abstract counts; the abstract counts are used here.
OSConcomitant chemotherapy, main question (101 trials, 18,951 patients across all timings of chemotherapy; the whole 2021 database has 107 trials and 19,805 patients)long term-updatemedian follow-up 6.5 yearsLacas 2021——HR 0.83 (95% CI 0.79–0.86)5-year absolute benefit 6.5% (10-year 3.6%). Efficacy decreased with age (p_trend = 0.03). Median follow-up of 6.5 years is for the 101 trials of the main question.
OSInduction chemotherapy added to locoregional treatment (main question)long term-updateLacas 2021——HR 0.96 (95% CI 0.90–1.01)Efficacy of induction chemotherapy decreased with poorer performance status (p_trend = 0.03).
OSAdjuvant chemotherapy added to locoregional treatment (main question)long term-updateLacas 2021——HR 1.02 (95% CI 0.92–1.13)
Results reported for MACH-NC
EndpointAnalysisLocoregional treatment plus chemotherapyLocoregional treatment aloneEffect
OS63 trials of locoregional treatment with or without chemotherapy (10,741 patients)primaryPignon 2000——HR 0.90 (95% CI 0.85–0.94)P<0.000163 trials, 10,741 patients; absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. No significant benefit with adjuvant or neoadjuvant chemotherapy; concomitant chemotherapy gave significant benefits, but heterogeneity prohibited firm conclusions (abstract).
OSThree larynx-preservation trials (602 patients): radical surgery plus radiotherapy versus neoadjuvant chemotherapy plus radiotherapy in responders (radical surgery and radiotherapy in non-responders)primaryPignon 2000——HR 1.19 (95% CI 0.97–1.46)Non-significant; the authors concluded that the organ-preservation procedure 'must remain investigational'.
OS50 trials of concomitant chemotherapylong term-updatePignon 2009——HR 0.81P<0.0001Absolute benefit 6.5% at 5 years. All 87 trials (16,485 patients) in the abstract: HR of death 0.88 (p<0.0001), absolute benefit 4.5% at 5 years. The paper's title cites 93 trials and 17,346 patients, which differs from the abstract counts; the abstract counts are used here.
OSConcomitant chemotherapy, main question (101 trials, 18,951 patients across all timings of chemotherapy; the whole 2021 database has 107 trials and 19,805 patients)long term-updatemedian follow-up 6.5 yearsLacas 2021——HR 0.83 (95% CI 0.79–0.86)5-year absolute benefit 6.5% (10-year 3.6%). Efficacy decreased with age (p_trend = 0.03). Median follow-up of 6.5 years is for the 101 trials of the main question.
OSInduction chemotherapy added to locoregional treatment (main question)long term-updateLacas 2021——HR 0.96 (95% CI 0.90–1.01)Efficacy of induction chemotherapy decreased with poorer performance status (p_trend = 0.03).
OSAdjuvant chemotherapy added to locoregional treatment (main question)long term-updateLacas 2021——HR 1.02 (95% CI 0.92–1.13)
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOSOSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.90.85–0.94
OS1.190.97–1.46
OS0.830.79–0.86
OS0.960.9–1.01
OS1.020.92–1.13
Primary publication: Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355(9208):949-55. PubMed

Appears in

Sources

  1. Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355(9208):949-55.

    PubMed

  2. Pignon JP, le Maître A, Maillard E, Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4-14.

    PubMedDOI

  3. Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, et al. 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. Radiother Oncol. 2021;156:281-293.

    PubMedDOI