PURPOSE: To investigate the efficacy of gefitinib as an adjuvant therapy for non–small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252 ), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non–small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m² on day 1) plus vinorelbine (25 mg/m² on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS: Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION: Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint inhibitor (ICI) treatment efficacy. The clinical efficacy of ICIs for non-small-cell lung cancer (NSCLC) patients harboring major mutations, such as EGFR or ALK mutations, is limited. We genotyped 190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy, and examined the efficacy in NSCLC patients with or without major mutations. Among the patients enrolled in the genotyping study, 47 patients harbored EGFR mutations, 25 patients had KRAS mutations, 5 patients had a HER2 mutation, 6 patients had a BRAF mutation, and 7 patients had ALK rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the rate of high PD-L1 expression (≥50%) was significantly higher in patients with ALK mutations. The progression-free survival was 0.6 (95% CI: 0.2–2.1) months for ALK-positive patients and 1.8 (95% CI: 1.2–2.1) months for EGFR-positive patients. All patients with ALK rearrangement showed disease progression within three months from the initiation of anti-PD-1 treatment. Our data suggested that ICI treatment was significantly less efficacious in patients with ALK rearrangement than in patients with EGFR mutations, and PD-L1 expression was not a critical biomarker for ICI treatment for patients with one of these mutations.

We sought to compare the latest data on postoperative pain between robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS), and to clarify the relationship between the number or placement of ports and postoperative pain in patients with lung cancer. Patients who underwent anatomical lung resection by RATS or VATS and whose chest tube was removed within 7 days were enrolled. The primary endpoint was the percentage of patients with a numeric rating scale (NRS) score ≤ 3 on postoperative day 30 (POD30). The target sample size was 400 patients. Four hundred five patients (RATS, n = 196; VATS, n = 209) managed at 12 institutions were included. Ninety-nine patients in the VATS group underwent a uniport procedure. Significant differences were observed between the RATS and VATS groups in the mean number of inserted ports (5.0 vs. 2.2), number of injured intercostal sites (2.9 vs. 1.9), largest wound size (3.4 vs. 3.7 cm), operation time (202 vs. 165 min), and use of epidural anesthesia or continuous nerve block (45 vs. 31 %). In the RATS and VATS groups, the rates of NRS≤3 on POD30 were 82.0 % and 94.7 % (95 %CI: -19.0 to -6.6 %), respectively, which could not prove noninferiority. However, in a multivariable analysis, the RATS approach was not proven to be a significant risk factor. In the current status of minimally invasive thoracic surgery in Japan, RATS involves a greater number of ports, longer operation time, and higher frequency of local anesthesia than VATS and may be inferior in terms of postoperative pain.