Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer.

Background: Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib.

Methods: ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib.

Differential properties of KRAS transversion and transition mutations in non-small cell lung cancer: associations with environmental factors and clinical outcomes.

Background: KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23-35% and 13-20% of all NSCLCs in white patients and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations and transition mutations, as well as their association with environmental factors and clinical outcome.

Prognostic impact of pretreatment T790M mutation on outcomes for patients with resected, EGFR-mutated, non-small cell lung cancer.

Background: Many previous studies have demonstrated that minor-frequency pretreatment T790M mutation (preT790M) could be detected by ultrasensitive methods in a considerable number of treatment-naïve, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) cases. However, the impact of preT790M in resected cases on prognosis remains unclear.

Methods: We previously reported that preT790M could be detected in 298 (79.

Can smoking duration alone replace pack-years to predict the risk of smoking-related oncogenic mutations in non-small cell lung cancer? A cross-sectional study in Japan.

Objective: To investigate whether smoking duration alone can replace pack-years to predict the risk of oncogenic mutations in non-small cell lung cancer (NSCLC).

Design: A cross-sectional study using the baseline dataset from the Japan Molecular Epidemiology for Lung Cancer Study.

Setting: Forty-three medical institutions nationwide in Japan.

Prospective Observational Study of Treatment Resistance-related Gene Screening Using Plasma Circulating Tumor DNA in Third-generation EGFR-TKI Osimertinib Therapy (Elucidator).

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits EGFR activating and EGFR T790M resistance mutations. Osimertinib was found to be more effective than first-generation EGFR-TKIs in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) harboring EGFR-positive mutations in a prior phase III trial. Osimertinib is, therefore, one of the most important standard therapies for EGFR mutation-positive patients.

Impact of somatic mutations on prognosis in resected non-small-cell lung cancer: The Japan Molecular Epidemiology for lung cancer study.

Background: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS).

Methods: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations.

Chemotherapy versus erlotinib as second-line treatment in patients with advanced non-small cell lung cancer and wild-type epidermal growth factor receptor: an individual patient data (IPD) analysis.

The efficacy of second-line treatment in patients with epidermal growth factor receptor (EGFR) wild-type tumours is still debatable. We assessed the efficacy of a standard second-line chemotherapy compared with erlotinib in an individual patient data approach for meta-analysis. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS).

Improvement of Mycobacterium abscessus Pulmonary Disease after Nivolumab Administration in a Patient with Advanced Non-small Cell Lung Cancer.

Nivolumab has become the standard second-line chemotherapy for non-small cell lung cancer. A 73-year-old man with stage IV non-small cell lung cancer received 6 cycles of chemotherapy with nab-paclitaxel/carboplatin/bevacizumab followed by 11 cycles of nab-paclitaxel/bevacizumab; however, treatment was stopped due to pneumothorax. One year after therapy started, a nodule appeared in the left upper lung and increased in size.

Clinical Characteristics of Liver Metastasis in Nivolumab-treated Patients with Non-small Cell Lung Cancer.

Background: Recent studies have revealed that liver metastasis is associated with poor outcomes after treatment using immune checkpoint inhibitors, although the cause remains unclear.

Patients And Methods: We retrospectively identified 201 patients at three Japanese Centers who received nivolumab for advanced non-small cell lung cancer between December 2015 and July 2016. The patients' baseline clinical characteristics and subsequent outcomes were compared according to liver metastasis status.

Association Between Imaging Findings of Airway Obstruction Adjacent to Lung Tumors and the Onset of Interstitial Lung Disease After Nivolumab.

Background: Compared to conventional cytotoxic chemotherapy, immune checkpoint inhibitors have shown a significant efficacy in the treatment of lung cancer. Although interstitial lung disease (ILD) is an important adverse event in immunotherapy, risk factors for ILD remain unclear.

Patients And Methods: In this multicenter cohort study (UMIN000025908), 201 patients who were treated with nivolumab were retrospectively reviewed.

Metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer: A retrospective multicenter trial.

Purpose: To conduct a retrospective multicenter trial to determine the significance of metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer.

Methods: This study was conducted across three medical centers in Japan. We retrospectively reviewed all patients who commenced nivolumab treatment at these centers between December 17, 2015 and July 31, 2016.

Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes.

The Association Between Chemotherapy Immediately Before Nivolumab and Outcomes Thereafter.

Background/aim: We investigated whether the efficacy and type of pre-nivolumab chemotherapy influence outcomes in non-small cell lung cancer patients following nivolumab treatment.

Patients And Methods: In this multicenter study, 199 patients treated with nivolumab were retrospectively reviewed. We analyzed the relationships between the clinical response to nivolumab and to chemotherapy administered immediately beforehand.

Correlation of Radiation Pneumonitis History Before Nivolumab with Onset of Interstitial Lung Disease and Progression-free Survival of Patients with Pre-treated Advanced Non-small Cell Lung Cancer.

Background/aim: Nivolumab has a promising efficacy for patients with non-small-cell lung cancer (NSCLC) as second-line or later treatment, and after radiotherapy as abscopal effect. However, the effects of radiation pneumonitis history before nivolumab have not been clarified. Therefore, we retrospectively analyzed the correlation of a history of radiation pneumonitis before nivolumab with onset of interstitial lung disease (ILD) and progression-free survival (PFS) after nivolumab treatment in patients with previously treated NSCLC.

Cerebrospinal Fluid Penetration Rate and Efficacy of Afatinib in Patients with EGFR Mutation-positive Non-small Cell Lung Cancer with Leptomeningeal Carcinomatosis: A Multicenter Prospective Study.

Background: Afatinib is an effective first-line treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid (CSF) penetration rate on the efficacy of afatinib in patients with central nervous system metastases. Therefore, we conducted a prospective multicenter trial to evaluate the CSF penetration rate and efficacy of afatinib in patients with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis.

Multiplex Ultrasensitive Genotyping of Patients with Non-Small Cell Lung Cancer for Epidermal Growth Factor Receptor (EGFR) Mutations by Means of Picodroplet Digital PCR.

Epidermal growth factor receptor (EGFR) mutations have been used as the strongest predictor of effectiveness of treatment with EGFR tyrosine kinase inhibitors (TKIs). Three most common EGFR mutations (L858R, exon 19 deletion, and T790M) are known to be major selection markers for EGFR-TKIs therapy. Here, we developed a multiplex picodroplet digital PCR (ddPCR) assay to detect 3 common EGFR mutations in 1 reaction.

Molecular Epidemiological Study on Passive Smoking and Estrogen Receptor Expression in Never-smokers with Non-small Cell Lung Cancer.

Background: Although sex hormones are thought to play an important role in the carcinogenesis of non-small cell lung cancer (NSCLC) in never-smokers, the causative mechanism remains unknown. Passive smoking (PS) is common among East Asian women and has been suggested to be a potential cause of the disease.

Methods: We systematically evaluated the expression of estrogen receptor (ER), the prevalence of PS, and genetic mutations using tumor samples from a prospectively registered cohort of never-smokers with lung cancer.

Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study.

Purpose: Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. However, their associations with environmental factors are not fully understood. We aimed to elucidate the relationship between tumor developmental biology and exposure to environmental factors.

Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR.

Introduction: While epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) lead to longer progression-free survival (PFS) when compared with conventional chemotherapy in non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR-TKI remains unclear in EGFR-wild-type (WT) NSCLC.

Areas Covered: This article reviews selected data from randomized trials regarding the use of TKIs in EGFR-WT NSCLC. Nine randomized phase III trials have compared EGFR-TKI with chemotherapy in NSCLC patients in a second or later line setting.

Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non-Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR.

Purpose: The resistance to the EGFR tyrosine kinase inhibitors (TKI) is a major concern in non-small cell lung cancer (NSCLC) treatment. T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies suggested that T790M mutation was also detected in TKI-naïve NSCLCs in a small cohort.

Molecular analysis of human papillomavirus in never-smokers with non-small cell lung cancer.

The causes of lung cancer in never-smokers remain unclear. The potential contribution of human papillomavirus (HPV) to the carcinogenesis of non-small cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.

Long-term complete response in a patient with disseminated pulmonary pleomorphic carcinoma induced by cisplatin and gemcitabine.

A 47-year-old man was referred to our department due to multiple metastases in the lungs and liver with pleural dissemination six weeks after undergoing curative surgery for lung pleomorphic carcinoma. He received two regimens of chemotherapy, both of which resulted in disease progression. Considering his good general condition, he was treated with cisplatin plus gemcitabine (GP).