Dataset Information

Novel active agents in patients with advanced NSCLC without driver mutations who have progressed after first-line chemotherapy.

ABSTRACT: Despite the efficacy of a number of first-line treatments, most patients with advanced-stage non-small cell lung cancer (NSCLC) experience disease progression that warrants further treatment. In this review, we examine the role of novel active agents for patients who progress after first-line therapy and who are not candidates for targeted therapies. More therapeutic options are needed for the management of patients with NSCLC after failure of first-line chemotherapy. A PubMed search was performed for articles from January 2012 to May 2015 using the keywords NSCLC, antiangiogenic, immunotherapy, second-line, novel therapies and English language articles only. Relevant papers were reviewed; papers outside that period were considered on a case-by-case basis. A search of oncology congresses was performed to identify relevant abstracts over this period. In recent years, antiangiogenic agents and immune checkpoint inhibitors have been added to our armamentarium to treat patients with advanced NSCLC who have progressed on first-line chemotherapy. These include nintedanib, a triple angiokinase inhibitor; ramucirumab, a vascular endothelial growth factor receptor-2 antibody; and nivolumab, pembrolizumab and atezolizumab, just three of a growing list of antibodies targeting the programmed death receptor-1 (PD-1)/PD ligand-1 pathway. Predictive and prognostic factors in NSCLC treatment will help to optimise treatment with these novel agents. The approval of new treatments for patients with NSCLC after the failure of first-line chemotherapy has increased options after a decade of few advances, and holds promise for future evolution of the management of NSCLC.

SUBMITTER: Manegold C

PROVIDER: S-EPMC5729303 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Novel active agents in patients with advanced NSCLC without driver mutations who have progressed after first-line chemotherapy.

Manegold Christian C Adjei Alex A Bussolino Federico F Cappuzzo Federico F Crino Lucio L Dziadziuszko Rafal R Ettinger David D Fennell Dean D Kerr Keith K Le Chevalier Thierry T Leighl Natasha N Papotti Mauro M Paz-Ares Luis L Pérol Maurice M Peters Solange S Pirker Robert R Quoix Elisabeth E Reck Martin M Smit Egbert E Vokes Everett E van Zandwijk Nico N Zhou Caicun C

ESMO open 20160101 6

Despite the efficacy of a number of first-line treatments, most patients with advanced-stage non-small cell lung cancer (NSCLC) experience disease progression that warrants further treatment. In this review, we examine the role of novel active agents for patients who progress after first-line therapy and who are not candidates for targeted therapies. More therapeutic options are needed for the management of patients with NSCLC after failure of first-line chemotherapy. A PubMed search was perform ...[more]

PMID: 29435365

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Project description:The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR?=?0.81, 95% CI 0.69-0.95, P?=?0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P?=?0.02). In selected patients by EGFR-mutation, both mutation positive (HR?=?0.48, 95% CI 0.28-0.83, P?=?0.009) and negative (HR?=?0.84, 95% CI 0.72-0.98, P?=?0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P?=?0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR?=?0.51, 95% CI 0.35-0.74, P?=?0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR?=?2.01, 95% CI 1.11-3.63; P?=?0.02) and diarrhea (RR?=?2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

Dataset Information

Novel active agents in patients with advanced NSCLC without driver mutations who have progressed after first-line chemotherapy.

Publications

Novel active agents in patients with advanced NSCLC without driver mutations who have progressed after first-line chemotherapy.

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