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Optimize the number of cycles of induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

ABSTRACT: Background: There is no conclusive on the optimal number of cycles of induction chemotherapy (IC) with the greatest benefit to patient survival. This study aimed to assess the efficiency and acute toxicities of different cycles of IC for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods: We reviewed data from patients with LA-NPC treated with IC plus concurrent chemoradiation (CCRT). Propensity score matching (PSM) was applied to match paired patients. After PSM, survival outcomes of matched patients were compared between two and three cycles of IC groups. Univariate and multivariate Cox regression analysis were carried out to identify potentially independent predictors. Treatment-related acute toxicities between the two groups were compared by Pearson X² test or Fisher's exact test. Results: In total, 189 pairs were selected. The median follow-up time was 60 months (range 5 to 126 months). There was no difference between two and three cycles of IC in terms of 5-year overall survival (87.0% vs. 89.7%, p = 0.991), distant metastasis-free survival (90.1% vs. 86.8%, p = 0.587), locoregional recurrence-free survival (97.0% vs. 93.8%, p = 0.488), or progression-free survival (79.4% vs. 79.3%, p = 0.896). Multivariate Cox analysis showed that T stage, N stage, and clinical stage were independent prognostic factors. Three cycles of IC were associated with a higher incidence of Grade 1-2 acute toxicity than two cycles during IC period. Conclusion: The efficacy of two cycles of IC achieved similar survival outcomes as three cycles and has a lower incidence of treatment-related acute toxicity.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC8771525 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDespite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC <induction chemotherapy> plus cisplatin CCRT <concurrent chemoradiotherapy>) for LANPC patients.MethodsFrom January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors.ResultsAfter PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064).ConclusionAdditiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Project description: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.

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Optimize the number of cycles of induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

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