Meta analysis
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients

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Abstract

Background

Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000.

Methods

The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment + chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated.

Results

Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p < 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p < 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p < 0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p = 0.003, test for trend).

Conclusion

The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.

Section snippets

Materials and methods

The methods were pre-specified in a protocol (copy available on request).

Results

The meta-analysis included 87 randomised trials (16,485 patients) comparing loco-regional treatment versus the same loco-regional treatment + chemotherapy. The trials included in the previous MACH-NC meta-analysis have been described previously [2]. Twenty-four new trials (5744 patients) evaluated chemotherapy concomitant with radiotherapy. One trial [5 of the Web-appendix] evaluated both adjuvant and concomitant chemotherapy. Data from one trial [11] that included 86 patients were lost, and two

Discussion

This updated individual patient data meta-analysis provides a reliable evaluation of the effect of chemotherapy in locally advanced head and neck cancer. Compared to the previous study, a large number of patients and randomised trials have been added and the follow-up has been markedly increased, including for the older trials. Consequently, the statistical power has been increased and we were able to undertake more complete analyses with new endpoints (effect of different types of

Role of the funding source

The sponsors of this study had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report.

Investigator contribution (see list of investigator at the end of the paper)

Secretariat: J.P.P., J.B., B.L., J.L.L., J.P.A. conceived, designed and supervised the study;

J.P.P., J.B. obtained funding;

C.A., N.S., A.L.M., E.M., J.P.P. participated in data collection and checking;

C.A., A.L.M., E.M., J.P.P. did statistical analyses;

J.P.P., J.B., A.L.M., E.M. wrote the draft, with revision from the other investigator.

The authors had full access to all the data and analyses and, after consultation with the collaborators, had final responsibility for the decision to submit for

Secretariat

Caroline Amand, Jean Pierre Armand, Jean Bourhis, Aurélie Le Maître, Bernard Luboinski, Emilie Maillard, Jean-Pierre Pignon, Jean-Louis Lefebvre, Nathalie Syz

Steering Committee

Jacques Bernier, Volker Budach, Arlene A. Forastiere, Lesley A. Stewart, Everett E. Vokes.

Investigators

D.J. Adelstein (Cleveland Clinic Foundation), J.P. Armand (Institut Claudius Regaud), C. Amand (Intitut Gustave-Roussy [IGR]), H. Audry (IGR), J.M. Bachaud (Institut Claudius Regaud), H.G. Bartelink (Netherlands Cancer Institute, Amsterdam), J.

Acknowledgements

The chief acknowledgement is to the trialists who agreed to share their data.

We also thank the following institutions for funding the investigators meeting or the meta-analysis project: Association pour la Recherche sur le Cancer (ARC No. 2015), Institut Gustave-Roussy, Ligue Nationale Contre le Cancer, Programme Hospitalier de Recherche Clinique (No. IDF 95009), Sanofi-Aventis.

We thank Denise Avenell, for secretarial assistance, Francine Courtial for electronic literature search, Charlotte

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