ESMO 2016: Meta-Analysis Confirms Superiority of Concomitant Over Induction Chemotherapy in Non-Metastatic HNSCC

Adding concommitant chemotherapy to loco-regional treatment or radiotherapy significantly improved overall survival

Patients with head and neck squamous cell carcinoma (HNSCC) achieved prolonged overall survival (OS) when concomitant chemotherapy was administered with local regional treatment (LRT) or radiotherapy, according to findings from a large meta-analysis reported on 10 October at the ESMO 2016 Congress in Copenhagen, Denmark. However, timing was important, as the survival benefit was not observed with the addition of induction chemotherapy.

Pierre Blanchard, Department of Radiation Therapy, Gustave Roussy Cancer Campus in Villejuif, France is a first author of the study and Prof. Jean Bourhis of the Département d'oncologie, Centre Hospitalier Universitaire Vaudois - CHUV, Lausanne, Switzerland presented at ESMO 2016 an update of the MACH-NC meta-analysis done previously by the MACH-NC group, which showed concomitant chemotherapy improved OS in patients with non-metastatic HNSCC.

Meta-analysis also showed that the gain in OS decreases with increasing age and worsening performance status

Dr. Blanchard and colleagues analysed individual patient data obtained from trials done between 1965 and 2010 in patients with non-metastatic HNSCC. The analysis compared 2 of the regimens used in the trials: Loco-regional treatment (LRT) was compared to LRT 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 OS.

This meta-analysis included current data from 2574 patients participating in 15 new trials in addition to updated patient data from 11 additional trials. The comparison of LRT versus LRT 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 tumour site in 35% of patients. Overall, 29% of patients had stage III tumours and 63% had stage IV tumours.

The analysis showed that adding chemotherapy to LRT significantly improved OS over sole LRT; the hazard ratio (HR) for the comparison was 0.89; 95% confidence interval (CI) 0.86, 0.92 (p < 0.0001). A significant interaction between treatment effect and the timing of chemotherapy was also observed, with improved OS being limited to concomitant chemotherapy, HR 0.83; 95% CI 0.79, 0.87 (p < 0.0001). The prolonged OS seen with concomitant chemotherapy translated to a 5-year absolute survival benefit (ABS) of 6.5 % and a 10-year ABS of 3.4%.

The OS 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 (p trend = 0.06) in patients aged 70 or more years, and HR 0.93; 95% CI 0.73, 1.19 (p trend = 0.07) for patients with PS of 2 or greater.

The analysis of induction chemotherapy plus radiotherapy compared to radiotherapy plus concomitant chemotherapy comprised data from 1214 patients participating in 8 trials confirmed the superiority of concomitant chemotherapy in prolonging on OS, HR 0.84; 95% CI 0.74, 0.95 (p = 0.007) and progression-free survival, HR 0.85; 95% CI 0.75, 0.96 (p = 0.008).

Conclusions

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

Disclosure

This study was funded by the French Ministry of Health (Programme d’actions integrees de recherche VADS), Ligue Nationale Contre le Cancer French National Cancer Institute (SHS 2014-141), National Cancer Institute, National Institutes of Health (CA180888 and CA180819), Hellenic Cooperative Oncology Group (HE R_5G).

Reference

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Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 100 randomized trials and 19,248 patients, on behalf of MACH-NC group

P. Blanchard, C. Landais, C. Petit, Q. Zhang, V. Grégoire, J. Tobias, B. Burtness, M.G. Ghi, F. Janot, J. Overgaard, G. Wolf, F. Lewin, R. Hitt, R. Corvo, V. Budach, A. Trotti, C. Fortpied, A. Hackshaw, J. Bourhis, J.-P. Pignon 

This study was funded by the French Ministry of Health (Programme d’actions integrees de recherche VADS), Ligue Nationale Contre le Cancer French National Cancer Institute (SHS 2014-141), National Cancer Institute, National Institutes of Health (CA180888 and CA180819), Hellenic Cooperative Oncology Group (HE R_5G).