Pierre Blanchard1, Anne Lee2, Sophie Marguet3, Julie Leclercq3, Wai Tong Ng2, Jun Ma4, Anthony T C Chan5, Pei-Yu Huang4, Ellen Benhamou1, Guopei Zhu6, Daniel T T Chua7, Yong Chen4, Hai-Qiang Mai8, Dora L W Kwong9, Shie Lee Cheah10, James Moon11, Yuk Tung12, Kwan-Hwa Chi13, George Fountzilas14, Li Zhang8, Edwin Pun Hui5, Tai-Xiang Lu8, Jean Bourhis15, Jean Pierre Pignon16. 1. Gustave-Roussy, Villejuif, France; Centre for Research in Epidemiology and Population Health, INSERM U1018, Paris-Saclay University, Villejuif, France. 2. Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. 3. Gustave-Roussy, Villejuif, France. 4. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China. 5. Partner State Key Laboratory of Oncology in South China, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China. 6. Fudan University Shanghai Cancer Center, Shanghai, PR China. 7. Hong Kong Sanatorium & Hospital, Hong Kong, China. 8. Sun Yat-sen University Cancer Center, Guangzhou, PR China. 9. Queen Mary Hospital, Hong Kong, China. 10. National Cancer Centre, Singapore, Singapore. 11. SWOG Statistical Center, Seattle, WA, USA. 12. Tuen Mun Hospital, Hong Kong, China. 13. Shin Kong Wu Ho-Su, Memorial Hospital, Tapei, Taiwan. 14. Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. 15. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 16. 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.
Abstract
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Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for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.
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.
Authors: Carlos Rodriguez-Galindo; Mark D Krailo; Matthew J Krasin; Li Huang; M Beth McCarville; John Hicks; Farzana Pashankar; Alberto S Pappo Journal: J Clin Oncol Date: 2019-09-25 Impact factor: 44.544
Authors: Federico Rotolo; Jean-Pierre Pignon; Jean Bourhis; Sophie Marguet; Julie Leclercq; Wai Tong Ng; Jun Ma; Anthony T C Chan; Pei-Yu Huang; Guopei Zhu; Daniel T T Chua; Yong Chen; Hai-Qiang Mai; Dora L W Kwong; Yoke Lim Soong; James Moon; Yuk Tung; Kwan-Hwa Chi; George Fountzilas; Li Zhang; Edwin Pun Hui; Anne W M Lee; Pierre Blanchard; Stefan Michiels Journal: J Natl Cancer Inst Date: 2017-04 Impact factor: 13.506
Authors: Sung Ho Moon; Kwan Ho Cho; Chang-Geol Lee; Ki Chang Keum; Yeon-Sil Kim; Hong-Gyun Wu; Jin Ho Kim; Yong Chan Ahn; Dongryul Oh; Jong Hoon Lee Journal: Strahlenther Onkol Date: 2016-03-14 Impact factor: 3.621