Indirect comparison of the efficacy of cetuximab and cisplatin in squamous cell carcinoma of the head and neck

Abstract

Background:

Cetuximab (Erbitux

*Erbitux is a registered trade name of Bristol–Myers Squibb, Princeton, NJ, USA.

) is the only new medical therapy for locally and regionally advanced SCCHN to be licensed in industrialized countries in the past 15 years and presents an alternative to cisplatin which is the current therapeutic standard. In the absence of a published head-to-head trial, we estimated the relative benefit of cetuximab and cisplatin using an indirect comparison methodology.

Methods:

We performed a systematic review of the Medline and Embase databases between 1998 and 2008 to find published trials of cisplatin plus radiotherapy vs. radiotherapy alone and synthesized the information with meta-analysis. Those results were combined with trial-based results of cetuximab plus radiotherapy vs. radiotherapy alone. Inclusion criteria stipulated that cisplatin be administered concurrently with radiation, the radiation protocol be comparable to the registration trial for cisplatin (once-daily, twice-daily, or concomitant boost) and cisplatin dosing be comparable to that in common use (i.e. day 1, 22 and 43 of treatment). Endpoints were locoregional control and overall survival. Two reviewers examined 269 abstracts which yielded four trials meeting the inclusion criteria.

Results:

There was little evidence of superiority of either platinum-based radiotherapy or cetuximab-based radiotherapy. All estimated hazard ratios were near 1.0 (equivalence), all confidence intervals spanned the null value (1.0), and no consistent pattern was observed regarding the direction of the effect. The results remained robust in sensitivity analysis.

Conclusion:

This is the first quantitative analysis allowing formal comparison between cetuximab and radiotherapy versus cisplatin and radiotherapy. Based on state-of-the-art methodology for indirect comparisons, it was not possible to identify either treatment regimen as superior in prolonging either locoregional control or overall survival. Until the publication of more studies, and particularly a head-to-head comparison, the two treatments may be considered equally efficacious when given alongside radiotherapy. The choice of treatment may focus on the toxicity profile of the medications.

Keywords::

• Chemotherapy
• Head and neck cancer
• Indirect comparisons
• Radiation

Transparency

Declaration of funding

This study was funded by Bristol–Myers Squibb.

Declaration of financial/other interest

ARL, KMJ and JS have disclosed that they are compensated by Oxford Outcomes as a consultant (ARL) or employees (KMJ, JS), a company that was contracted by Bristol-Myers Squibb to conduct this study. B.D., J.R.P. and M.C. have disclosed that they are employees of Bristol–Myers Squibb. M.Ch. has disclosed that he has no relevant financial relationships.

CMRO peer reviewers may have received honoraria for their peer review work. Peer reviewer number 1 has disclosed that he is a consultant for Merck. Peer reviewer number 2 has disclosed that he has no relevant financial relationships.

Acknowledgments

A poster of this material was presented American Society for Therapeutic Radiology and Oncology meeting in February 2010.

Notes

*Erbitux is a registered trade name of Bristol–Myers Squibb, Princeton, NJ, USA.

*Erbitux, Bristol-Myers Squibb, Princeton, NJ USA.