Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+).
We ...conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design.
Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36–0.58, P < 0.0001 and overall response rate (ORR) (HR 2.08, 95% CI 1.75–2.46, P < 0.0001) over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials.
In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ∼25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation.
Introduction: The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1. ...Given that resistance occurs within approximately 12 months, in order to develop more potent inhibitors and to increase drug penetration to CNS, innovative ALK-inhibitors were developed. Second-generation ALK inhibitors Ceritinib (LDK378), Alectinib (CH5424802/RO5424802) and Brigatinib (AP26113) have shown significant clinical activity, and were rapidly approved by regulatory agencies. In addition, early clinical data demonstrated that 3
rd
generation ALK-inhibitors Lorlatinib (PF-06463922), Entrectinib (RxDx-101) and Ensartinib (X-398) provided promising advantages in terms of both clinical activity and safety.
Areas covered: In this review, the efficacy and tolerability of Crizotinib for 1
st
and 2
nd
-line treatment, and the clinical and preclinical data that led to the development of innovative second and third generation ALK-inhibitors are described.
Expert opinion: The better characterization of the mechanisms of resistance to Crizotinib led to the development of newest drugs, which are active both after Crizotinib failure and in patients naïve from ALK-inhibitors. Tumor characterization at disease progression will allow to further personalize the treatment by establishing optimal sequences, which represent tough challenges for the future research in this field of cancer treatment.
...colonoscopy could have produced false negative results for several reasons, including misinterpretation of what was visualised or failure to perform adequate biopsy of the lesions seen. 6 In this ...case, it could be intriguing to compare the ability of faecal DNA panel versus that of the Hemoccult II test in predicting the early occurrence of "advanced neoplasia" when colonoscopy misses the disease.
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