Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study

Satoshi Igawa,1 Taihei Ono,1 Masashi Kasajima,1 Mikiko Ishihara,1 Yasuhiro Hiyoshi,1 Seiichiro Kusuhara,1 Noriko Nishinarita,1 Tomoya Fukui,1 Masaru Kubota,1 Jiichiro Sasaki,2 Mitsufuji Hisashi,3 Masanori Yokoba,4 Masato Katagiri,4 Katsuhiko Naoki11Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 2Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 3Kitasato University School of Nursing, Sagamihara-city, Kanagawa, Japan; 4School of Allied Health Sciences, Kitasato University, Sagamihara-city, Kanagawa 252-0373, JapanPurpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation.Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation.Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS.Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.Keywords: EGFR genotype, non-small cell lung carcinoma, osimertinib, efficac

Prognostic significance of the 8th edition of the TNM classification for patients with extensive disease small cell lung cancer

Masayuki Shirasawa,1,* Tomoya Fukui,1,* Seiichiro Kusuhara,1 Yasuhiro Hiyoshi,1 Mikiko Ishihara,1 Masashi Kasajima,1 Yoshiro Nakahara,1 Sakiko Otani,1 Satoshi Igawa,1 Masanori Yokoba,2 Hisashi Mitsufuji,3 Masaru Kubota,1 Masato Katagiri,1 Jiichiro Sasaki,4 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan; 2Department of Medical Laboratory, Kitasato University School of Allied Health Sciences, Kanagawa, Japan; 3Fundamental Nursing, Kitasato University School of Nursing, Kanagawa, Japan; 4Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan *These authors contributed equally to this work Background: Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear.Methods: This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016.Results: According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4–22.2) months in the M1b group vs 7.3 (95% CI 5.7–8.9) months in the M1c group (P<0.001). Multivariate analysis showed that in addition to the known prognostic factors such as performance status, serum albumin, and lactate dehydrogenase, M descriptor was a prognostic factor (HR 1.95, 95% CI 1.38–2.77; P<0.001).Conclusion: The 8th TNM classification has a prognostic value in SCLC. Similarly to NSCLC, treatment approaches should be considered on the basis of the 8th TNM classification, especially stage IVA separate from stage IVB in ED-SCLC patients. Keywords: small cell lung cancer, extensive disease, TNM stage, prognosi

Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease

Satoshi Igawa,1 Noriko Nishinarita,1 Akira Takakura,1 Takahiro Ozawa,1 Shinya Harada,1 Seiichiro Kusuhara,1 Hideyuki Niwa,2 Shinji Hosotani,1 Hideyuki Sone,1 Yoshiro Nakahara,1,3 Tomoya Fukui,1 Hisashi Mitsufuji,4 Masanori Yokoba,5 Masaru Kubota,1 Masato Katagiri,5 Jiichiro Sasaki,6 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan; 2Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Aichi, Japan; 3Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Kanagawa, Japan; 4Kitasato University School of Nursing, Sagamihara 252-0329, Kanagawa, Japan; 5School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan; 6Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan Background: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. Patients and methods: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. Results: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59–83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. Conclusion: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD. Keywords: interstitial lung disease, non-small-cell lung cancer, carboplatin, nab-paclitaxe