PATIENTS AND METHODS: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned.
RESULTS: Overall (N = 55), median PFS was 4.9 months versus 4.4 months [stratified HR, 0.67; 90% CI, 0.35-1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04-0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02-0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1-56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy.
CONCLUSIONS: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
METHOD: A meta-analysis was conducted to determine the potential impact of isometric exercise on IOP and OPP. The literature on the relationship between isometric resistance exercise and IOP was systematically searched according to the "Cochrane Handbook" in the databases of Pubmed, Web of Science, EBSCO, and Scopus through December 31, 2020. The search terms used were "exercise," "train," "isometric," "intraocular pressure," and "ocular perfusion pressure," and the mean differences of the data were analyzed using the Stata 16.0 software, with a 95% confidence interval.
RESULTS: A total of 13 studies, which included 268 adult participants consisting of 162 men and 106 women, were selected. All the exercise programs that were included were isometric resistance exercises of the lower limbs with intervention times of 1min, 2min, or 6min. The increase in IOP after intervention was as follows: I2=87.1%, P=0.001 using random-effects model combined statistics, SMD=1.03 (0.48, 1.59), and the increase in OPP was as follows: I2=94.5%, P=0.001 using random-effects model combined statistics, SMD=2.94 (1.65, 4.22), with both results showing high heterogeneity.
CONCLUSION: As isometric exercise may cause an increase in IOP and OPP, therefore, people with glaucoma and related high risk should perform isometric exercise with caution.