The Most Efficacious Induction Chemotherapy Regimen for Locoregionally Advanced Nasopharyngeal Carcinoma: A Network Meta-Analysis

Abstract

BackgroundInduction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.MethodsAll randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.ResultsDC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08–0.73), 0.43 (0.24–0.77), and 0.54 (0.27–1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24–0.88), 0.51 (0.34–0.77), and 0.49 (0.20–1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.ConclusionsGiven its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.

A Single-Arm Phase 2 Trial on Induction Chemotherapy Followed by Concurrent Chemoradiation in Nasopharyngeal Carcinoma Using a Reduced Cumulative Dose of Cisplatin

“…The study published by Mai and colleagues concluded that IMRT plus 2 cycles of concurrent 100 mg/m 2 cisplatin without induction chemotherapy could be an alternative option for patients with low-risk locoregionally advanced NPC with Epstein-Barr virus (EBV) DNA levels < 4000 copies/ml ( 28 ). But for LA NPC, several recently published randomized phase III trials conducted in a similar ethnic patient cohort demonstrated that IC followed by concurrent systemic therapy/RT had better survival benefit than concurrent systemic therapy/RT alone ( 10 – 12 , 29 , 30 ). Concerning different IC regimens in LA NPC, a network meta-analysis of 9 clinical trials showed that docetaxel + cisplatin (DC), gemcitabine + cisplatin (GP), and PX had favorable OS benefits.…”

“…Concerning different IC regimens in LA NPC, a network meta-analysis of 9 clinical trials showed that docetaxel + cisplatin (DC), gemcitabine + cisplatin (GP), and PX had favorable OS benefits. GP and PX were the most promising IC regimens to date in the era of IMRT ( 10 ). In comparison with induction GP-CCRT, as reported by Zhang and colleagues ( 11 ), our trial showed similar results in terms of 3-year survival outcomes and toxicities.…”

“…The proportion of patients that received 3 concurrent cycles was 33% in the induction-PX arm. Most induction platinum-based doublet chemotherapy regimens implemented a cisplatin dose of 75-80mg/m 2 for 2 to 3 cycles ( 10 – 12 ). Furthermore, some evidence suggested that a cumulative cisplatin dose of 200 mg/m 2 during CCRT may be adequate to achieve a survival benefit ( 13 , 14 ).…”

The best choice of induction chemotherapy for patients with locally advanced nasopharyngeal carcinoma: Bayesian network meta‐analysis

“…In addition, the results of two recent NMAs were compromised by the results of Hui's phase II RCT including only 65 patients and limitation of a comprehensive analysis of CR, LRRFS, DMFS, and AEs. Their conclusion that the combination regimen of docetaxel and cisplatin was the best efficacious induction regimen for patients with locally advanced NPC differed from the National Comprehensive Cancer Network (NCCN) guideline recommended regimen and was something to be considered with caution 17,18 . In this scenario, our NMA including all updated phase III RCTs and comprehensively comparing the efficacy and safety of different ICs in patients with locally advanced NPC based on a frequency and Bayesian framework, played a non‐negligible role in providing rational evidence for the role of ICs and the choice of the optimal IC regimen.…”

“…Recently, with the new randomized controlled trials (RCTs) on the effectiveness of IC constantly explored, it is necessary to update the benefits of neoadjuvant chemotherapy and the understanding of IC regimens. Earlier network meta‐analysis (NMA) has not yet identified the optimal IC regimen, and the reliability of conclusions was undermined by the small samples of phase II RCTs without inclusion of the updated phase III RCTs 15–18 . Our NMA will further elucidate the role of ICs in patients with locally advanced NPC and determine the expected neoadjuvant chemotherapy option on the basis of all eligible phase III RCTs.…”