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Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis - 01/06/23

Doi : 10.1016/S1470-2045(23)00163-8 
Claire Petit, MD a, c, d, Anne Lee, ProfMD e, f, Jun Ma, ProfMD g, Benjamin Lacas, PhD b, c, d, Wai Tong Ng, MD e, f, Anthony T C Chan, ProfMD h, Ruey-Long Hong, ProfMD i, Ming-Yuan Chen, ProfMD j, Lei Chen, MD j, Wen-Fei Li, MD j, Pei-Yu Huang, MD j, Terence Tan, MD k, Roger K C Ngan, MD f, Guopei Zhu, MD l, Hai-Qiang Mai, ProfMD j, Edwin P Hui, MD h, George Fountzilas, ProfMD m, n, o, Li Zhang, ProfMD j, Alexandra Carmel, MSc b, c, d, Dora L W Kwong, MD f, James Moon, MD p, Jean Bourhis, ProfMD d, q, Anne Auperin, MD b, c, d, Jean-Pierre Pignon, MD b, c, d, Pierre Blanchard, ProfMD a, c, d,
on behalf of the

MAC-NPC Collaborative Group*

  Members listed in Supplementary Material
Anne Aupérin, Pierre Blanchard, Ellen Benhamou, Jean Bourhis, Alexandra Carmel, Somvilai Chakrabandhu, Anthony TC Chan, Lei Chen, Ming-Yuan Chen, Qiu-Yan Chen, Yong Chen, Richard J Chappell, Horace Choi, Daniel TT Chua, Melvien Lee Kiang Chua, George Fountzilas, Julian Higgins, Ming Huang Hong, Ruey-Long Hong, Pei-Yu Huang, Edwin Pun Hui, Chin-Fu Hsiao, Michael Kam, Georgia Angeliki Koliou, Dora L W Kwong, Benjamin Lacas, Shu-Chuan Lai, Ka On Lam, Michael L LeBlanc, Anne WM Lee, Ho Fun Victor Lee, Wen Fei Li, Yoke Lim, Brigette Ma, Jun Ma, Hai-Qiang Mai, Frankie Mo, James Moon, Wai Tong Ng, Roger Ngan, Camille Ollivier, Brian O'Sullivan, Claire Petit, Jean-Pierre Pignon, Sharon X Poh, Gerta Rücker, Jonathan Sham, Yoke Lim Soong, Ying Sun, Terence Tan, Lin-Quan Tang, Yuk Tung, Joseph Wee, Xuang Wu, Tingting Xu, Li Zhang, Yuan Zhang, Guopei Zhu

a Department of Radiation Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Gustave Roussy, Villejuif, France 
b Service de Biostatistique et d’Epidémiologie, Gustave Roussy, Villejuif, France 
c Oncostat U1018 INSERM, Ligue Nationale Contre le Cancer, Villejuif, France 
d Groupe d’Oncologie Radiothérapie Tête Et Cou, Tours, France 
e Clinical Oncology Center, University of Hong Kong–Shenzhen Hospital, University of Hong Kong, Hong Kong Special Administrative Region, China 
f Department of Clinical Oncology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China 
g Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China 
h State Key Laboratory of Translational Oncology, Hong Kong Cancer Institute, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China 
i Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan 
j Sun Yat-sen University Cancer Center, Guangzhou, China 
k National Cancer Center, Singapore 
l Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, China 
m Aristotle University of Thessaloniki, Thessaloniki, Greece 
n Hellenic Cooperative Oncology Group, Athens, Greece 
o German Oncology Center, Limassol, Cyprus 
p Southwest Oncology Group Statistics and Data Management Center, Seattle, WA, USA 
q Department of Radiotherapy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland 

* Correspondence to: Prof Pierre Blanchard, Department of Radiation Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Gustave Roussy, 94800 Villejuif, France Department of Radiation Oncology Gustave Roussy Cancer Campus Université Paris-Saclay Gustave Roussy Villejuif 94800 France

Summary

Background

The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis.

Methods

For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524.

Findings

The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2–13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59–0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69–0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75–1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%).

Interpretation

The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma.

Funding

Institut National du Cancer and Ligue Nationale Contre le Cancer.

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P. 611-623 - juin 2023 Retour au numéro
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