Pan-Driver-Negatives versus Epidermal Growth Factor Receptor Mutants for C-Stage IA Lung Adenocarcinoma with Ground-Glass Opacity

Purpose: We aimed to verify the prognosis of epidermal growth factor receptor (EGFR) mutation of clinical (c)-stage IA lung adenocarcinoma with the ground-glass opacity (GGO) component.Methods: We evaluated 226 cases of surgically resected c-stage IA lung adenocarcinoma with GGO component. Endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan–Meier analysis and the log-rank test were used to estimate the survival differences. Prognostic factors were assessed using the univariable and multivariable Cox proportional hazards model.Results: Among the 226 cases, 177 cases harbored the EGFR-mutant adenocarcinoma with the GGO component. The mean duration of follow-up time was 54.4 ± 1.2 months. The 5-year OS and RFS did not differ significantly between the EGFR-mutant and wild-type groups (5-year OS 100% vs. 94.3%, hazard ratio [HR] 0.276, P = 0.168; 5-year RFS 94.7% vs. 95.7%, HR 0.873, P = 0.864). Multivariable Cox hazard model revealed that radiologically solid component size (P = 0.010) and pathological node-positive (P = 0.036) were significant predictors of an inferior RFS.Conclusion: EGFR-mutant was not a prognostic factor of OS and RFS for c-stage IA lung adenocarcinoma with the GGO component. Radiologically solid component size and pathological lymph node status were independent prognostic factors of worse RFS.     

Correlation of EGFR mutation subtypes and survival in surgically treated brain metastasis from non-small-cell lung cancer

ObjectiveEpidermal growth factor receptor (EGFR) mutation is a positive prognostic factor for survival in patients with non–small-cell lung cancer (NSCLC). In such patients, brain metastasis signifies negative outcomes. Patients with NSCLC brain metastasis that may benefit from neurosurgery is under investigation. We aim to investigate the impact of different mutation loci in surgically treated NSCLC brain metastasis patients.MethodsThis retrospective cohort study included patients with NSCLC brain metastasis who underwent brain lesionectomy, followed by radiotherapy and chemotherapy or targeted therapy. Demographics and tumor characteristics were compared between the EGFR mutant type and wild type groups. Postoperative survival and risk factors were analyzed using log rank and Cox regression methods.ResultsOverall, 101 patients were included, with 57 belonging to the EGFR mutant type group and 44 to the EGFR wild type group. The median postoperative survival was 17 months for the entire cohort, with the duration being 19 and 14 months for EGFR mutant type and wild type patients (p = 0.013), respectively. Multivariate analysis revealed that exon 19 del (p = 0.02) and a high Karnofsky Performance Scale score (p < 0.01) were independent positive prognostic factors to predict survival. The timing of development of the brain metastasis or the location of the intracranial metastasis was not associated with EGFR mutations.ConclusionEGFR mutations are associated with better survival outcomes in patients with NSCLC brain metastasis suitable for surgical treatment. This advantage was attributed to patients having a specific mutation of exon 19 deletion.     

Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non–small cell lung cancer

ObjectiveMultimodality treatment for resectable non–small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non–small cell lung cancer and promising preoperatively in small clinical trials for resectable non–small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.MethodsPatients with stage IB to select IIIB resectable non–small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0.ResultsFrom April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached.ConclusionsNeoadjuvant atezolizumab in resectable stage IB to IIIB non–small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non–small cell lung cancer.     

Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non–small cell lung cancer: A phase II study

IntroductionCurrently, limited data on tyrosine kinase inhibitors as neoadjuvant therapy exist. This prospective study aimed to investigate the efficacy and safety of preoperative gefitinib in patients with stage II-IIIA operable non–small cell lung cancer (NSCLC).MethodsThis was a single-arm, phase II trial performed in the Shanghai Cancer Center. Between August 2013 and October 2015, patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled. Patients were treated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints were the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival, and adverse events (AEs). ORR was defined as the proportion of patients achieving complete response or partial response radiologically. MPR was defined as no more than 10% viable tumor.ResultsOf the 35 eligible patients, 33 were considered as intention-to-treat population. ORR, the primary endpoint, was 54.5% (95% confidence interval [CI], 37.7-70.7), and the rate of MPR was 24.2% (95% CI, 11.9-40.4). Median DFS was 33.5 months (95% CI, 19.7-47.3); median overall survival was not reached. Skin toxicity (24/35,68.6%) and gastrointestinal symptoms (17/35,48.6%) were the most common AEs; no patients reported grade 3 or 4 AEs. After surgery, 4 patients experienced chylothorax (4/33,12.1%). Patients with MPR had a prolonged survival compared with those without (DFS, P = .019).ConclusionsNeoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations. Patients with MPR were associated with improved survival.