Abstract
Guidance concerning tyrosine kinase inhibitors (TKIs) for patients with wild type epidermal growth factor receptor (EGFR) and advanced non–small-cell lung cancer (NSCLC) after first-line treatment is unclear. We assessed the effect of TKIs as second-line therapy and maintenance therapy after first-line chemotherapy in two systematic reviews and meta-analyses, focusing on patients without EGFR mutations. Systematic searches were completed and data extracted from eligible randomized controlled trials. Three analytical approaches were used to maximize available data. Fourteen trials of second-line treatment (4388 patients) were included. Results showed the effect of TKIs on progression-free survival (PFS) depended on EGFR status (interaction hazard ratio [HR], 2.69; P = .004). Chemotherapy benefited patients with wild type EGFR (HR, 1.31; P < .0001), TKIs benefited patients with mutations (HR, 0.34; P = .0002). Based on 12 trials (85% of randomized patients) the benefits of TKIs on PFS decreased with increasing proportions of patients with wild type EGFR (P = .014). Six trials of maintenance therapy (2697 patients) were included. Results showed that although the effect of TKIs on PFS depended on EGFR status (interaction HR, 3.58; P < .0001), all benefited from TKIs (wild type EGFR: HR, 0.82; P = .01; mutated EGFR: HR, 0.24; P < .0001). There was a suggestion that benefits of TKIs on PFS decreased with increasing proportions of patients with wild type EGFR (P = .11). Chemotherapy should be standard second-line treatment for patients with advanced NSCLC and wild type EGFR. TKIs might be unsuitable for unselected patients. TKIs appear to benefit all patients compared with no active treatment as maintenance treatment, however, direct comparisons with chemotherapy are needed.
Highlights
After reports of clinical trials[1,2,3,4,5] and clinical guidelines (National Institute for Health and Care Excellence [NICE] TA258 and National Comprehensive Cancer Network [NCCN] Non-Small-Cell Lung-17), the use of the tyrosine kinase inhibitors (TKIs), erlotinibSubmitted: Sep 10, 2014; Revised: Nov 13, 2014; Accepted: Nov 18, 2014; Epub: Nov 22, 2014With the exception of a few modern trials that only recruited patients with wild type disease,[8,9] most evaluations of these drugs have been in unselected patients
We explored whether the TKI used or the chemotherapy regimen used affected the effect of TKIs
We identified 25 potentially eligible randomized controlled trials (RCTs), of TKIs as secondline treatment (n 1⁄4 18) and maintenance treatment (n 1⁄4 7; Figure 1)
Summary
With the exception of a few modern trials that only recruited patients with wild type disease,[8,9] most evaluations of these drugs have been in unselected patients. Many of these trials did not test for EGFR mutations systematically, their results are reported either for all randomized patients, ignoring EGFR mutation status, or for the subset of patients in whom the status was known. Results of these trials are mixed and interpretation difficult. When only a subset of the randomized patients within a given trial were tested, pooling results might introduce bias,[14] not least because we cannot be certain that these patients were representative
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
