According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.

Trastuzumab emtansine (T-DM1), an anti-erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry [IHC] score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years; male sex, 47%; performance status of 0 to 1, 80%; HER2 status IHC 3+, 33%; HER status IHC 2+/fluorescence in situ hybridization-positive, 20%; and exon 20 mutation, 47%. The median number of delivered cycles was 3 (range 1-11). One patient achieved a partial response with an objective response rate of 6.7% (90% confidence interval: 0.2-32.0). With a median follow-up time of 9.2 months, the median progression-free survival time and median survival time were 2.0 and 10.9 months, respectively. Grade 3 or 4 adverse events included thrombocytopenia (40%) and hepatotoxicity (20%) without any treatment-related deaths. T-DM1 had a limited efficacy for HER2-positive NSCLC in our cohort. Applying the concept of precision medicine to tumors appears challenging; thus, additional molecular approaches are warranted.

Introduction Immune checkpoint inhibitors (ICIs) have demonstrated long survival for the treatment of advanced non-small cell lung cancer (NSCLC). However, the effect and safety of ICI rechallenge have not been fully evaluated. The aim of this study was to investigate the efficacy and safety of ICI rechallenge in NSCLC patients. Methods We defined ‘rechallenge’ as re-administration of ICIs for patients who were previously treated with ICIs and discontinued treatment for any reason, and received subsequent chemotherapy. We retrospectively analyzed the histories of 434 patients with advanced NSCLC who received ICIs from December 2015 to December 2017 at seven centers. Results A total of 317 patients discontinued the ICI treatment, and 14 patients (4.4%) received ICI rechallenge. All 14 patients discontinued the first ICI due to disease progression. Eight patients received the same kind of ICIs, and six patients received different ICIs. Median progression-free survival and overall survival were 1.5 months [95% confidence interval (CI): 0.8–2.6] and 6.5 months [95% CI: 1.4–19.0], respectively. The objective response rate was 7.1%, and the disease control rate was 21.4%. Two of three patients who achieved at least a stable disease, received radiotherapy between the first and second ICIs. Adverse events were not significantly different compared with the first ICIs. Conclusions In this study, the effect of ICI rechallenge was limited. Careful consideration of the administration of ICI rechallenge is necessary. This report involved a small number of cases, so further large prospective studies are warranted to confirm the efficacy of ICI rechallenge and to investigate predictive markers to identify a patient population in which ICI rechallenge is effective.

BackgroundOsimertinib is an essential drug to treat non-small-cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation, and rebiopsy is necessary to detect this mutation. However, the significance of repeat rebiopsy in NSCLC patients whose first rebiopsy was T790M-negative remains unclear. We used a retrospective cohort to clarify this issue.MethodsWe reviewed the medical records of patients with NSCLC harboring EGFR mutations who underwent EGFR tyrosine kinase inhibitor (TKI) treatment at Okayama University Hospital between January 2015 and January 2017.ResultsOf 102 patients with EGFR-mutant NSCLC, 55 underwent rebiopsy after acquired resistance to prior EGFR TKIs. Pre-existing activating EGFR mutations were found in all 55 rebiopsied samples. Of the 55 samples, 25 were T790M-positive (45%). Among the remaining 30 patients (T790M-negative on the first rebiopsy), 21 underwent additional rebiopsies following interval therapy. Of the 21 patients, 11 were T790M-positive on the second rebiopsy and 1 on the third. We also evaluated the efficacy of osimertinib in patients who needed a repeat rebiopsy to detect the T790M mutation. Osimertinib showed good activity with an objective response rate of 50%.ConclusionsRepeat rebiopsy increases the ability to detect a secondary mutation (T790M) in EGFR.

An anaphylactic reaction during a cesarean section occurs rarely, and rocuronium is thought to be one of the common agents causing perioperative anaphylaxis. Here we report an anaphylactic shock after cesarean section that is suggested to be induced by the rocuronium–sugammadex complex. A 36-year-old primigravida underwent an elective cesarean section under general anesthesia due to placenta previa. While the operation was completed uneventfully, she developed anaphylactic shock following sugammadex administration. She was successfully managed with rapid treatments. Serum tryptase level was significantly elevated. Although sugammadex was first suspected to be the causative agent, the result of intradermal skin tests with sugammadex were negative. Surprisingly, a subsequent intradermal test with undiluted rocuronium caused the patient to fall into a state of shock. Furthermore, a later skin-prick test with pre-mixed rocuronium–sugammadex complex also revealed a strong positive reaction, and a test with only rocuronium showed negative. We finally concluded that the rocuronium–sugammadex complex is the causative agent in this case. To the best of our knowledge, this is the first report suggesting anaphylaxis caused by the rocuronium–sugammadex complex. This case highlights the importance of appropriate examinations to determinate the pathogenesis of anaphylaxis in order to establish risk reduction strategies.