Journal article
Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis.
- Blanchard P Gustave-Roussy, Villejuif, France; Centre for Research in Epidemiology and Population Health, INSERM U1018, Paris-Saclay University, Villejuif, France.
- Lee A Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
- Marguet S Gustave-Roussy, Villejuif, France.
- Leclercq J Gustave-Roussy, Villejuif, France.
- Ng WT Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
- Ma J Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
- Chan AT Partner State Key Laboratory of Oncology in South China, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
- Huang PY Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
- Benhamou E Gustave-Roussy, Villejuif, France; Centre for Research in Epidemiology and Population Health, INSERM U1018, Paris-Saclay University, Villejuif, France.
- Zhu G Fudan University Shanghai Cancer Center, Shanghai, PR China.
- Chua DT Hong Kong Sanatorium & Hospital, Hong Kong, China.
- Chen Y Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
- Mai HQ Sun Yat-sen University Cancer Center, Guangzhou, PR China.
- Kwong DL Queen Mary Hospital, Hong Kong, China.
- Cheah SL National Cancer Centre, Singapore, Singapore.
- Moon J SWOG Statistical Center, Seattle, WA, USA.
- Tung Y Tuen Mun Hospital, Hong Kong, China.
- Chi KH Shin Kong Wu Ho-Su, Memorial Hospital, Tapei, Taiwan.
- Fountzilas G Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
- Zhang L Sun Yat-sen University Cancer Center, Guangzhou, PR China.
- Hui EP Partner State Key Laboratory of Oncology in South China, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
- Lu TX Sun Yat-sen University Cancer Center, Guangzhou, PR China.
- Bourhis J Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Pignon JP Gustave-Roussy, Villejuif, France; Centre for Research in Epidemiology and Population Health, INSERM U1018, Paris-Saclay University, Villejuif, France. Electronic address: jean-pierre.pignon@gustaveroussy.fr.
- 2015-05-11
Published in:
- The Lancet. Oncology. - 2015
Carcinoma
Chemotherapy, Adjuvant
Clinical Trials as Topic
Combined Modality Therapy
Disease-Free Survival
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms
Treatment Outcome
English
BACKGROUND
A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy.
METHODS
We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis.
FINDINGS
We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2-11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73-0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5-9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56-0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70-0·93) but not adjuvant chemotherapy alone (0·87, 0·68-1·12) or induction chemotherapy alone (0·96, 0·80-1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69-0·81), locoregional control (0·73, 0·64-0·83), distant control (0·67, 0·59-0·75), and cancer mortality (0·76, 0·69-0·84).
INTERPRETATION
Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed.
FUNDING
French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.
A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy.
METHODS
We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis.
FINDINGS
We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2-11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73-0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5-9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56-0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70-0·93) but not adjuvant chemotherapy alone (0·87, 0·68-1·12) or induction chemotherapy alone (0·96, 0·80-1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69-0·81), locoregional control (0·73, 0·64-0·83), distant control (0·67, 0·59-0·75), and cancer mortality (0·76, 0·69-0·84).
INTERPRETATION
Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed.
FUNDING
French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/S1470-2045(15)70126-9
- PMID 25957714
- Persistent URL
- https://sonar.ch/global/documents/20411
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