ESMO 2016: Meta-analysis Confirms Superiority of Concomitant Over Induction Chemotherapy in Nonmetastatic Head and Neck Cancer

Key Points

  • The analysis showed that adding chemotherapy to LRT significantly improved OS over sole LRT; the hazard ratio (HR) for the comparison was 0.89.
  • A significant interaction between treatment effect and the timing of chemotherapy was also observed, with improved OS being limited to concomitant chemotherapy. The prolonged OS seen with concomitant chemotherapy translated to a 5-year absolute survival benefit of 6.5 % and a 10-year absolute survival benefit of 3.4%.
  • An interaction test done on data from recent trials of concomitant chemotherapy revealed a trend towards decreased efficacy with increasing age and poorer performance status in patients aged 70 or more years, and for patients with performance status of 2 or greater.

Patients with head and neck squamous cell carcinoma achieved prolonged overall survival when concomitant chemotherapy was administered with locoregional treatment or radiotherapy, according to findings from a large meta-analysis reported by Blanchard et al at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen, Denmark (Abstract 950O). However, timing was important, as the survival benefit was not observed with the addition of induction chemotherapy.

Pierre Blanchard, MD, PhD, of the Department of Radiation Therapy at Gustave Roussy Cancer Campus in Villejuif, France, is a first author of the study, and Jean Bourhis, MD, PhD, of the Département d'oncologie, Centre Hospitalier Universitaire Vaudois–CHUV in Lausanne, Switzerland, presented an update of the meta-analysis of chemotherapy in head and neck cancer (MACH-NC) done previously by the MACH-NC group, which showed concomitant chemotherapy improved overall survival in patients with nonmetastatic head and neck squamous cell carcinoma.

Meta-analysis Resources

Dr. Blanchard and colleagues analyzed individual patient data obtained from trials done between 1965 and 2010 in patients with nonmetastatic head and neck squamous cell carcinoma. The analysis compared two of the regimens used in the trials: locoregional treatment was compared to locoregional treatment plus chemotherapy, and induction chemotherapy plus radiotherapy was compared to radiotherapy plus concomitant (or alternating) chemotherapy. The investigators used a fixed effect model, and treatment comparison was evaluated using the log-rank test, stratified by trial. The primary endpoint of the study was overall survival.

This meta-analysis included current data from 2,574 patients participating in 15 new trials in addition to updated patient data from 11 additional trials. The comparison of locoregional treatment vs locoregional treatment plus chemotherapy comprised data of 18,394 patients taking part in 94 trials, with a median follow-up of 6.7 years.

The oropharynx was the most frequently involved tumor site (35% of patients). Overall, 29% of patients had stage III tumors and 63% had stage IV tumors.

Meta-analysis Findings

The analysis showed that adding chemotherapy to locoregional treatment significantly improved overall survival over sole locoregional treatment; the hazard ratio (HR) for the comparison was 0.89 (95% confidence interval [CI] = 0.86–0.92; P < .0001). A significant interaction between treatment effect and the timing of chemotherapy was also observed, with improved overall survival being limited to concomitant chemotherapy (HR = 0.83, 95% CI = 0.79–0.87; P < .0001). The prolonged overall survival seen with concomitant chemotherapy translated to a 5-year absolute survival benefit of 6.5% and a 10-year absolute survival benefit of 3.4%.

The overall survival was not improved with the addition of induction chemotherapy (HR = 0.97, 95% CI = 0.91–1.03).

An interaction test done on data from recent trials of concomitant chemotherapy revealed a trend towards decreased efficacy with increasing age and poorer performance status (PS) (HR = 1.00, 95% CI = 0.81–1.23; Ptrend = .06) in patients aged 70 or more years and for patients with PS of 2 or greater (HR = 0.93, 95% CI = 0.73–1.19; Ptrend = .07).

The analysis of induction chemotherapy plus radiotherapy compared to radiotherapy plus concomitant chemotherapy comprised data from 1,214 patients participating in eight trials confirmed the superiority of concomitant chemotherapy in prolonging on overall survival (HR = 0.84, 95% CI = 0.74–0.95; P = .007) and progression-free survival (HR = 0.85, 95% CI = 0.75–0.96; P = .008).

The authors concluded that this updated meta-analysis with longer patient follow-up confirmed the superiority of adding concomitant chemotherapy to locoregional therapy or radiotherapy in locally advanced head and neck squamous cell carcinoma as compared to induction chemotherapy treatment. They noted that they are continuing a study of patterns of relapse and toxicity.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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