Dataset Information

Molecular Targeted Therapy in the Management of Recurrent and Metastatic Nasopharyngeal Carcinoma: A Comprehensive Literature Review.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is the most frequent malignancy arising in the nasopharynx. NPC, to a larger degree, substantially differs from the other malignancies of the head and neck, in terms of incidence, etiology, risk factors, molecular pathogenesis, clinical behavior, management and prognosis. Fundamentally, the management of NPC is entirely guided by the disease stage. Favorably, patients with early- stage disease have encouraging survival outcomes with stand-alone radiation therapy (RT), specifically following the emergence of intensity-modulated RT (IMRT). The reported five-year local control rates are outstanding, and they range from 70% to 90%. Unfortunately, around one-third (30%) of patients presents with loco-regional or distant recurrences, despite rigorous curative treatment in the intermediate (stage II) and advanced (stage III-IVB) NPC disease. At the present time, the management of recurrent and metastatic NPC is largely discouraging and presents significant challenges to the treating physicians. Broadly speaking, there are three management schemes utilized in the management of recurrent and metastatic NPC, namely: (i) palliative systemic chemotherapy, (ii) molecular targeted therapy, and (iii) immunotherapy. The goal of this study is to holistically review the existing body of literature on the utility and safety of molecular targeted therapy in the management of patients with recurrent and metastatic NPC, with a special focus on vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) targets.

SUBMITTER: Almobarak AA

PROVIDER: S-EPMC6505721 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Molecular Targeted Therapy in the Management of Recurrent and Metastatic Nasopharyngeal Carcinoma: A Comprehensive Literature Review.

Almobarak Abdulaziz A AA Jebreel Alaeddin B AB Abu-Zaid Ahmed A

Cureus 20190309 3

Nasopharyngeal carcinoma (NPC) is the most frequent malignancy arising in the nasopharynx. NPC, to a larger degree, substantially differs from the other malignancies of the head and neck, in terms of incidence, etiology, risk factors, molecular pathogenesis, clinical behavior, management and prognosis. Fundamentally, the management of NPC is entirely guided by the disease stage. Favorably, patients with early- stage disease have encouraging survival outcomes with stand-alone radiation therapy (R ...[more]

PMID: 31114729

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Project description:BackgroundThe majority of published studies in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of progression-free survival (PFS) and overall survival (OS) outcomes, therefore, is difficult. This study aim to analyse existent literature to estimate the relative efficacy of available systemic regimens in RM-NPC, as well as provide estimates of aggregate OS and PFS.MethodsWe conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating cytotoxic and molecularly targeted agents in adult patients with RM-NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and Student's t-test were performed for all identified studies (model A). For studies that published analysable Kaplan-Meier curves, survival data were extracted and marginal proportional hazards models were constructed (model B).ResultsA total of 56 studies were identified and included in model A, 26 of which had analysable Kaplan-Meier curves and were included in model B. The 26 studies in model B had significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7, P=0.002). For patients receiving first line chemotherapy, the estimated median OS was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95% CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+), the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5 months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first-line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting, the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by model B (95% CI, 4.7-5.6).ConclusionsWe present the first aggregate estimates of OS and PFS for RM-NPC patients receiving first and second-line or higher treatment settings, which could inform the design of future clinical trials in this disease setting.

Project description:To assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p < 0.05). The ITC regimen also conferred a significant improvement in OS when comparing to C alone (HR 0.336, 95%CI 0.123-0.915, p = 0.033). The IT and IC regimens achieved a nearly identical PFS (HR 0.955, 95%CI 0.515-1.77, p = 0.884), although the IT regimen was associated with a lower occurrence of SAEs in contrast to the IC regimen (p < 0.05). In addition, the IT regimen demonstrated superior PFS (HR 0.583, 95%CI 0.345-0.985, p = 0.044) and fewer SAEs when compared to C alone (p < 0.05). These findings collectively support the notion that the combination of ICIs, target and chemotherapy exhibits robust antitumor activity in previously treated R/M NPC patients, without a significant increase in adverse events.

Dataset Information

Molecular Targeted Therapy in the Management of Recurrent and Metastatic Nasopharyngeal Carcinoma: A Comprehensive Literature Review.

Publications

Molecular Targeted Therapy in the Management of Recurrent and Metastatic Nasopharyngeal Carcinoma: A Comprehensive Literature Review.

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