PURPOSE Lazertinib is a potent, central nervous system (CNS)–penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This global, phase 3 study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS Patients were ≥18 years with no prior systemic anti-cancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomized 1:1 to lazertinib 240 mg once daily (qd) orally (po) or gefitinib 250 mg qd po, stratified by mutation status and race. The primary endpoint was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 vs 9.7 months; hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34 to 0.58; P<0.001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P=0.116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.
Introduction:We conducted a study to evaluate the dosimetric feasibility of mask-based cobalt-60 fractionated stereotactic radiotherapy (mcfSRT) with the Leksell Gamma Knifeâ Icon TM device. Methods: Eleven patients with intracranial tumours were selected for this dosimetry study. These patients, previously treated with volumetric arc therapy (VMAT), were re-planned using mcfSRT. Target volume coverage, conformity/gradient indices, doses to organs at risk and treatment times were compared between the mcfSRT and VMAT plans. Two-sided paired Wilcoxon signed-rank test was used to compare differences between the two plans. Results: The V95 for PTV was similar between fractionated mcfSRT and VMAT (P = 0.47). The conformity index and gradient indices were 0.9 and 3.3, respectively, for mcfSRT compared to 0.7 and 4.2, respectively, for VMAT (P < 0.001 and 0.004, respectively). The radiation exposure to normal brain was lower for mcfSRT across V10, V25 and V50 compared with VMAT (P = 0.007, <0.001 and <0.001, respectively). The median D0.1cc for optic nerve and chiasm as well as the median D50 to the hippocampi were lower for mcfSRT compared to VMAT. Median beam-on time for mcfSRT was 9.7 min per fraction, compared to 0.9 min for VMAT (P = 0.002). Conclusion: mcfSRT plans achieve equivalent target volume coverage, improved conformity and gradient indices, and reduced radiation doses to organs at risk as compared with VMAT plans. These results suggest superior dosimetric parameters for mcfSRT plans and can form the basis for future prospective studies.
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