. 2021 Nov 26:32:59-68.

doi: 10.1016/j.ctro.2021.11.007. eCollection 2022 Jan.

Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients

Pierre Blanchard^{1

2}, Anne W M Lee³, Alexandra Carmel^{2

4}, Ng Wai Tong³, Jun Ma⁵, Anthony T C Chan⁶, Ruey Long Hong⁷, Ming-Yuan Chen⁸, Lei Chen⁸, Wen-Fei Li⁸, Pei-Yu Huang⁸, Dora L W Kwong⁹, Sharon S X Poh¹⁰, Roger Ngan³, Hai-Qiang Mai⁸, Camille Ollivier^{2

4}, George Fountzilas¹¹, Li Zhang⁸, Jean Bourhis¹², Anne Aupérin^{2

4}, Benjamin Lacas^{2

4}, Jean-Pierre Pignon^{2

4}; MAC-NPC collaborative Group

Collaborators, Affiliations

Collaborators

MAC-NPC collaborative Group:
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, Melvin Lee Kiang Chua, George Fountzilas, Julian Higgins, Ming-Huang Hong, Ruey-Long Hong, Pei-Yu Huang, Edwin Pun Hui, C F Hsiao, Michael Kam, Georgia Angeliki Koliou, Dora Lw Kwong, Benjamin Lacas, Shu-Chuan Lai, Ka On Lam, Michael L LeBlanc, Anne Wm Lee, Ho Fun Victor Lee, Wen Fei Li, 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

Affiliations

¹ Department of Radiation Oncology, Gustave Roussy Cancer Campus, Université Paris-Sud, Université Paris-Saclay, Villejuif, France Gustave-Roussy, Villejuif, France.
² Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Villejuif, France.
³ University of Hong Kong - Shenzhen Hospital, University of Hong-Kong, China.
⁴ Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France.
⁵ 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 510060, China.
⁶ State Key Laboratory of Translational Oncology, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong, China.
⁷ National Taiwan University Hospital, Taipei, Taiwan.
⁸ Sun Yat-sen University Cancer Center, Guangzhou, China.
⁹ Department of Clinical Oncology, University of Hong Kong, Hong Kong, China.
¹⁰ National Cancer Center, Singapore.
¹¹ Aristotle University of Thessaloniki School of Medicine, Thessaloniki, and Hellenic Cooperative Oncology Group, Athens, Greece and German Oncology Center, Limassol, Cyprus.
¹² Department of Radiotherapy, Centre hospitalier universitaire vaudois, Lausanne, Switzerland.

PMID: 34935776
PMCID: PMC8660702
DOI: 10.1016/j.ctro.2021.11.007

Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients

Pierre Blanchard et al. Clin Transl Radiat Oncol. 2021.

. 2021 Nov 26:32:59-68.

doi: 10.1016/j.ctro.2021.11.007. eCollection 2022 Jan.

Authors

Collaborators

MAC-NPC collaborative Group:
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, Melvin Lee Kiang Chua, George Fountzilas, Julian Higgins, Ming-Huang Hong, Ruey-Long Hong, Pei-Yu Huang, Edwin Pun Hui, C F Hsiao, Michael Kam, Georgia Angeliki Koliou, Dora Lw Kwong, Benjamin Lacas, Shu-Chuan Lai, Ka On Lam, Michael L LeBlanc, Anne Wm Lee, Ho Fun Victor Lee, Wen Fei Li, 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

Affiliations

¹ Department of Radiation Oncology, Gustave Roussy Cancer Campus, Université Paris-Sud, Université Paris-Saclay, Villejuif, France Gustave-Roussy, Villejuif, France.
² Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Villejuif, France.
³ University of Hong Kong - Shenzhen Hospital, University of Hong-Kong, China.
⁴ Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France.
⁵ 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 510060, China.
⁶ State Key Laboratory of Translational Oncology, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong, China.
⁷ National Taiwan University Hospital, Taipei, Taiwan.
⁸ Sun Yat-sen University Cancer Center, Guangzhou, China.
⁹ Department of Clinical Oncology, University of Hong Kong, Hong Kong, China.
¹⁰ National Cancer Center, Singapore.
¹¹ Aristotle University of Thessaloniki School of Medicine, Thessaloniki, and Hellenic Cooperative Oncology Group, Athens, Greece and German Oncology Center, Limassol, Cyprus.
¹² Department of Radiotherapy, Centre hospitalier universitaire vaudois, Lausanne, Switzerland.

PMID: 34935776
PMCID: PMC8660702
DOI: 10.1016/j.ctro.2021.11.007

Abstract

Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC.

Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified.

Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect.

Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.

Keywords: Chemotherapy; Individual patient data; Meta-analysis; Nasopharynx carcinoma; Randomized trials.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Forest plots for (A) overall survival and (B) progression-free survival with hazard ratios by timing of chemotherapy.

**Fig. 2**
Survival curves for overall survival by subsets of chemotherapy timing. A: Induction, B: Concomitant, C: Adjuvant, D: Concomitant + adjuvant, E: Induction (concomitant).

**Fig. 3**
Survival curves for progression-free survival by subsets of chemotherapy timing. A: Induction, B: Concomitant, C: Adjuvant, D: Concomitant + adjuvant, E: Induction (concomitant).

**Fig. 4**
Survival curves for cancer and non-cancer deaths.

See this image and copyright information in PMC

References

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1. Chen Y.-P., Chan A.T.C., Le Q.-T., Blanchard P., Sun Y., Ma J. Nasopharyngeal carcinoma. Lancet. 2019;394(10192):64–80. - PubMed
1. Blanchard P., Lee A., Marguet S., Leclercq J., Ng W.T., Ma J., et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015;16(6):645–655. - PubMed
1. Ribassin-Majed L., Marguet S., Lee A.W.M., Ng W.T., Ma J., Chan A.T.C., et al. What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol. 2017;35(5):498–505. - PMC - PubMed
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Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients

Collaborators

Affiliations

Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Further reading

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