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Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). In addition, in EU countries, nintedanib plus docetaxel is used for patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. Here, we report a case of advanced NSCLC in a patient with IPF successfully treated with nintedanib monotherapy. A 69-year-old man was diagnosed with NSCLC complicated by IPF. After three lines of chemotherapy, he still had progressive disease. Because his IPF had also progressed, requiring supplemental oxygen, we decided to start best supportive care and introduced nintedanib to treat his IPF. One month later, we observed a partial remission of the primary tumor and pleural disseminations without severe adverse events. Nintedanib monotherapy might therefore be an effective therapeutic choice for NSCLC in patients with IPF who are unable to tolerate cytotoxic chemotherapy. KEY POINTS: Efficacy of nintedanib administered in a NSCLC patient with IPF. Nintedanib monotherapy might be a therapeutic option for NSCLC patients with IPF who are unable to tolerate chemotherapy.

Background Adjuvant chemotherapy with platinum‐based regimens for completely resected early‐stage non‐small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials. Objectives We conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S‐1 for patients with completely resected stage II to IIIA NSCLC. Methods Patients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S‐1 at 80–120 mg/bodyweight per day for two weeks, followed by one‐week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two‐year survival rate. Results A total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1–4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6–91.4%). Two‐year disease‐free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied. Conclusions Carboplatin and oral S‐1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients. Key points Carboplatin and oral S‐1 had modest survival benefit but this regimen was not tolerable. Fatal pulmonary embolism occurred in this regimen.

Pembrolizumab has become the standard first-line treatment for non-small cell lung cancer (NSCLC) patients with high PD-L1expression. MET exon 14 skipping is a rare mutation typically found in older, female, and non-smoking patients with NSCLC. Herein, we report the case of a 71-year-old non-smoking woman who was diagnosed with NSCLC in the left lung. EGFR mutation and ALK fusion were not detected. Because the biopsy specimen showed high PD-L1 expression with a tumor proportion score of 95%, pembrolizumab was introduced as first-line therapy, but resulted in no clinical benefit. The patient was subsequently administered chemotherapy with carboplatin and pemetrexed, leading to remarkable tumor shrinkage. A next-generation sequencing panel analysis revealed a MET exon 14 skipping mutation. Thus, pembrolizumab might not be effective for NSCLC patients with MET exon 14 skipping mutations, even if PD-L1 expression is high.

Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for mutant non-small cell lung cancer (NSCLC), was approved in Japan in 2014. This study evaluated clinical outcomes of afatinib in real-world practice. Medical records of patients who received afatinib for advanced EGFR-mutant NSCLC were retrospectively reviewed. In total, 128 patients were analyzed. Seventy-six patients received afatinib as the first-line setting and 52 as the re-challenge setting (i.e., after failure of prior first-generation TKI). There was no difference in patient characteristics, such as age, sex, and PS, between the first-line and the re-challenge settings. In the first-line setting, the median progression-free survival (PFS) was 17.8 months (95% confidence interval [CI] 13.7-21.5 months). The overall survival (OS) was 39.5 months (95% CI 34.4- not reached). The response rate (RR) was 64.4%. Subset analysis indicated that patients with dose reduction showed longer PFS than those without dose reduction (18.5 months versus 7.9 months) (P = 0.016). In the re-challenge setting, the median PFS was 8.0 months (95% CI 4.9-9.5 months). The RR was 25%. Most common adverse events leading to dose modification or treatment discontinuation included diarrhea, paronychia, and oral mucositis in both settings. Interstitial lung disease occurred in 5.4% (7/128). In the real-world practice in Japan, afatinib showed comparable or better efficacy compared with that shown in previous clinical trials in both the first-line and the re-challenge settings.

The present retrospective study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring driver mutations. Patients with NSCLC harboring driver mutations who received ICIs (nivolumab or pembrolizumab) were reviewed in Hirosaki University and Aomori Prefectural Central Hospital. There were 139 patients who received molecular targeted drugs, including 24 patients treated with ICIs. Patient characteristics were as follows: Male/female, 5/19; median age 68 (range 39–82); smoking/non-smoking, 6/18; PS 0–1/2, 20/4; driver mutation status, EGFR/ALK/RET/ROS1: 21/1/1/1. The overall response rate was 16.7% [95% confidence interval (CI), 7.0–37.1%] and the disease control rate was 33.4% (95% CI, 18.9–55.1%). The median progression-free survival (PFS) time was 62 days (95% CI 52–81 days). In the patients who had been treated by the preceding tyrosine kinase inhibitor (TKI) for >1 year, the PFS time was 110 days. On the other hand, in the patients who had received a TKI for less than a year, the PFS time was 56 days, which was significantly shorter (P=0.012). To conclude, some of the patients with NSCLC harboring driver mutation could benefit from ICIs, and the duration of previous TKI treatment may be associated with the efficacy.

Background: The INPULSIS trials revealed that nintedanib reduced the decline in lung function in patients with idiopathic pulmonary fibrosis. We aimed to evaluate the efficacy and safety of nintedanib in Japanese idiopathic pulmonary fibrosis patients in real-world settings. Method: Medical records of idiopathic pulmonary fibrosis patients, who received treatment with nintedanib in five institutions between July 2015 and June 2017, were reviewed. Patients with % forced vital capacity ⩾50% and % predicted diffusing capacity of the lung carbon monoxide ⩾30% were classified as the moderate group and those with more impaired lung functions as the severe group. Result: Among 158 patients analyzed, 132 (84.6%) were classified as the moderate group and 26 (15.4%) as the severe group. In the moderate group, changes in forced vital capacity in 12 months were significantly different between before and after nintedanib administration (−253 ± 163 vs −125 ± 235 mL; p = 0.0027). In contrast, changes in forced vital capacity in 12 months were not significantly changed by nintedanib treatment in the severe group (−353 ± 250 vs −112 ± 341 mL; p = 0.2374). Incidence of acute exacerbation was higher in the severe group than in the moderate group (30.8% vs 18.9%). The overall survival of the moderate and the severe groups was 17.2 and 10.1 months. Conclusion: In real-world practice, nintedanib showed comparable efficacy to those observed in previous trials. In the severe group, the efficacy of nintedanib might be limited.

Sarcoidosis is an inflammatory granulomatous disease that is systemic, but bone involvement is uncommon. A 68-year-old man was referred to our hospital complaining of right shoulder pain with numbness. Computed tomography revealed systemic lymphadenopathy and multiple bone lesions. Because malignant lymphoma with a mass lesion protruding into the vertebral canal was considered, he underwent urgent radiotherapy. Thereafter, a needle biopsy of the left parasternal node was performed and showed epithelioid granulomas, confirming a diagnosis of sarcoidosis. Since his neurologic symptoms improved, the patient was not given systemic corticosteroids. Radiotherapy may be useful for local control of bone sarcoidosis.