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

Dora L.W Kwong,Pei-Yu Huang,Alexandra Carmel,Li Zhang,Anthony T.C Chan,Camille Ollivier,Jun Ma,Pierre Blanchard,George Fountzilas,Benjamin Lacas,Ng Wai Tong,Jean Bourhis,Lei Chen,Anne Aupérin,Wen‐Fei Li ,Ming‐Yuan Chen ,Sharon Shuxian Poh ,Ruey‐Long Hong ,Anne Wm Lee ,Hai‐Qiang Mai ,Roger K.c Ngan ,Jean‐Pierre Pignon

doi:10.1016/j.ctro.2021.11.007

Abstract

PurposeChemotherapy, 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. MethodsPublished or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified.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. ResultsEighteen 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. ConclusionThis 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.

Highlights

With >129 000 new cases globally in 2018, nasopharyngeal carci noma (NPC) remains a major public health issue especially in endemic areas
While the impact of age had not been demonstrated in previous MAC-nasopharyngeal carcinoma (NPC) rounds, maybe due to a lack of power, it seems clear that age is associated with treatment effect, the effect being larger in younger patients and not significant in patients older than 60 years
Potential explanations could be related to poor tolerance, increased risk of toxicity leading to lower chemotherapy dose intensity received

Summary

Introduction

With >129 000 new cases globally in 2018, nasopharyngeal carci noma (NPC) remains a major public health issue especially in endemic areas. The best sequence remains to be found and there is a controversy over the benefit of adding induction or adjuvant chemotherapy when concurrent chemoradiotherapy is given. Since the publication of the previous meta-analysis of chemotherapy in nasopharyngeal cancer MAC-NPC) [3,4], multiple randomized trials have been conducted and novel induction regimens using taxane or gemcitabine have been studied [5,6,7]. Quantitative plasma EBV DNA value at baseline and after chemoradiotherapy has a major prognostic role for recurrence and survival. Whether EBV DNA bears a predictive value for guiding personalized use of adjuvant chemotherapy remains to be demonstrated, as the first trial using EBV DNA after che moradiotherapy to plan additional chemotherapy was reported negative [8]

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Results

Conclusion