Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation.

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry).

Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single-arm, phase 2 trial (ABC Study).

BACKGROUND: Preclinical studies suggested that the addition of bevacizumab could overcome acquired resistance (AR) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the clinical efficacy and safety of a combination of afatinib and bevacizumab after AR. METHODS: Patients with EGFR-mutant non-small cell lung cancer after AR were enrolled during any line of therapy. Afatinib was prescribed at 30 mg, and 15 mg/kg bevacizumab was administered every 3 weeks until progression. RESULTS: Between October 2014 and May 2017, 32 eligible patients were evaluated. The mutation subtypes were Del-19 (20 [63%]), L858R (11 [34%]), and L861Q (1 [3%]). T790M was detected in 14 patients (44%). The median number of prior regimens was 4 (range, 1-10). Six patients obtained a partial response, and 23 had stable disease; this resulted in an objective response rate (ORR) of 18.8% (95% confidence interval [CI], 7.2%-36.4%) and a disease control rate of 90.7% (95% CI, 75.0%-98.0%). The median progression-free survival (PFS) was 6.3 months (95% CI, 3.9-8.7 months). The ORRs and median PFS times of T790M+ and T790M- patients were 14.3% and 22.2%, respectively, and 6.3 and 7.1 months, respectively; those of Del-19 and L858R patients were 20.0% and 11.1%, respectively, and 6.3 and 5.1 months, respectively. Grade 3 or higher adverse events (incidence ≥ 10%) included paronychia (25%), hypertension (41%), and proteinuria (19%). There were no treatment-related deaths, interstitial lung disease, or bevacizumab-associated severe bleeding. CONCLUSIONS: Afatinib plus bevacizumab demonstrated clinical efficacy and safety after AR to EGFR TKIs and could be a therapeutic salvage option for T790M- populations.

The association between erythromycin monotherapy for Mycobacterium avium complex lung disease and cross-resistance to clarithromycin: A retrospective case-series study.

Long-term, low-dose erythromycin monotherapy, based on the anti-inflammatory effects of macrolides, has been reported to have the potential to suppress the exacerbation of Mycobacterium avium complex (MAC) lung disease with less toxicity. It remains unclear whether erythromycin monotherapy induces cross-resistance to clarithromycin, a key drug for MAC. To clarify this point, we conducted a retrospective, single-center, case-series study on patients with MAC lung disease who underwent erythromycin monotherapy for at least 6 months. Drug susceptibility tests, before and after erythromycin treatment initiation, were analyzed. Thirty-three patients were included in our study. All 33 patients showed susceptibility to clarithromycin for MAC both before and after erythromycin monotherapy. There was no significant difference in clarithromycin minimum inhibitory concentrations between before and after erythromycin treatment (median difference = 0 µg/ml; P = .313, Wilcoxon's signed-rank test). We conclude that erythromycin monotherapy for MAC lung disease may not induce cross-resistance to clarithromycin.

[THE GENETIC EXAMINATION OF BRONCHIAL LAVAGE ENABLES THE PROMPT DIAGNOSIS OF PULMONARY MYCOBACTERIUM KANSASII--A CASE REPORT].

A 59-year-old man with chronic obstructive pulmonary disease and bronchial asthma presented at our hospital with an abnormal shadow on the chest radiograph, which was obtained as part of a routine medical examination. Computed tomography of the chest revealed two nodules in the right upper lung with the longest diameter measuring 29 mm and 10 mm, respectively. A granulomatous disease was strongly suspected based on the histological features of the transbronchial lung biopsy specimen. Results of smear examination for mycobacteria and genetic examination of the bronchial lavage aspirate by the transcription reverse transcription concerted (TRC) reaction method for Mycobacterium tuberculosis and M. avium complex (MAC), were both negative. However, three days after the bronchoscopic examination, an additional genetic examination by the TRC method confirmed the diagnosis of M. kansasii infection. About two weeks later, the culture results were positive and M. kansasii infection was re-confirmed with the DNA probe method. The patient responded well to treatment with a combination of isoniazid, rifampicin, and ethambutol. In Japan, among the nontuberculous mycobacterial infections, the prevalence of pulmonary M.kansasii disease is second only to infection with MAC. However, it is often difficult to distinguish this disease from pulmonary tuberculosis. In this patient, a genetic examination with the TRC method enabled a prompt diagnosis of M. kansasii infection. The TRC method appears to be a useful tool for diagnosing nontubercular mycobacterial infections.

[Safe treatment of lung squamous cell carcinoma with nanoparticle albumin-bound Paclitaxel in a patient with a previous hypersensitivity reaction after docetaxel administration].

A 61-year-old man was diagnosed with lung squamous cell carcinoma in the lower lobe of the right lung. He had received first-line chemotherapy consisting of cisplatin and docetaxel (DTX); however, an allergic/hypersensitivity reaction occurred shortly after administration of the second course of DTX. Thirty-nine months later, he received nanoparticle albumin-bound paclitaxel (nab-PTX) as sixth-line chemotherapy, which did not produce a hypersensitivity reaction. Hypersensitivity after DTX administration may have been due to the DTX vehicle. Therefore, nab-PTX administered under close supervision is a valid therapeutic option in similar cases.

Impact of serum eicosapentaenoic acid/arachidonic acid ratio on overall survival in lung cancer patients treated with pembrolizumab: a pilot study.

This pilot study analyzed the dietary patterns of patients with non-small cell lung cancer undergoing initial pembrolizumab, an immune checkpoint inhibitor (ICI), treatment in the month before treatment. Serum fatty acid fractions and their associations with ICI treatment efficacy were also investigated. The results showed that long-term survivors (those who survived for ≥ 3 years) consumed significantly more seafood than short-term survivors (those who survived for < 3 years). Furthermore, the serum levels of eicosapentaenoic acid (EPA) as well as the ratio of EPA to arachidonic acid (EPA/AA) were higher in the long-term survivors than those in the short-term survivors. The group with a high serum EPA/AA ratio had a significantly higher overall survival rate after ICI treatment than the group with a low serum EPA/AA ratio. In conclusion, higher dietary seafood consumption may improve OS in lung cancer patients treated with ICI and the serum EPA/AA ratio may be a useful biomarker for determining the efficacy of ICI treatment. Thus, supplements that increase the serum EPA/AA ratio could serve as new nutritional interventions for enhancing the efficacy of ICI treatment. However, further large-scale case and intervention studies are required.

Pulmonary disease caused by rapidly growing mycobacteria: a retrospective study of 44 cases in Japan.

BACKGROUND: The features of pulmonary disease caused by rapidly growing mycobacteria (RGM) have not been sufficiently documented. OBJECTIVES: To establish these features, we retrospectively evaluated 44 patients. METHODS: We screened respiratory isolates at the National Toneyama Hospital (Osaka, Japan) between 2003 and 2007. Diagnosis was based on the latest guidelines of the American Thoracic Society. The patients were classified into 3 types according to their radiographic findings: fibrocavitary, nodular bronchiectatic and unclassified variant. RESULTS: We obtained 1,348 nontuberculous mycobacteria respiratory isolates from 1,187 patients, including 119 RGM isolates from 100 patients. Forty-four of these 100 patients were definitively diagnosed with respiratory disease due to RGM. The most common pathogen was Mycobacterium abscessus, which accounted for 65.9% of cases, followed by Mycobacterium fortuitum at 20.5%. There was a statistically significant difference in smoking history between patients infected with these 4 RGM species (excluding those with an unknown smoking history; p = 0.039). The overall evaluation of radiographic findings revealed 18.2% as fibrocavitary, 43.2% as nodular bronchiectatic and 38.6% as unclassified variants in these 44 patients. There was a significant difference in radiographic findings between the 4 RGM species (p = 0.002). There was also a significant difference in radiographic findings between M. abscessus and M. fortuitum infected patients (p = 0.022). CONCLUSIONS: Patients with M. abscessus seem to have less of a smoking history and more frequent nodular bronchiectatic radiographic patterns than patients with M. fortuitum. In contrast, fibrocavitary patterns might be more frequent with M. fortuitum infection.

Alternating Therapy With Osimertinib and Afatinib Blockades EGFR Secondary Mutation in EGFR-Mutant Lung Cancer: A Single-Arm Phase II Trial.

BACKGROUND: Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has limited treatment options for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Although osimertinib or afatinib alone induced drug-resistant clones with EGFR secondary mutation in a preclinical model, its combination prevented the appearance of these mutations. We investigated alternating-dose therapy of osimertinib and afatinib in patients with EGFR-mutant NSCLC in a single-arm Phase II trial. METHODS: Treatment-naïve patients with stage IV NSCLC harboring an activating EGFR mutation were enrolled. Alternating cycles of osimertinib (80 mg/day) followed by afatinib (20 mg/day) were administered every 8 weeks. Genomic analysis was performed using circulating tumor DNA obtained before and after the treatment. RESULTS: Among the 46 enrolled patients, the median progression-free survival was 20.2 months. The overall response rate was 69.6%. The median overall survival was not reached. Among the 26 plasma samples obtained after the acquisition of resistance, 3 showed an increased MET gene copy number, and 1 showed BRAF mutation. Meanwhile, no EGFR secondary mutation was detected. CONCLUSION: The efficacy of our treatment was not significantly different from osimertinib alone, as reported previously in untreated advanced NSCLC patients with EGFR mutations. Although the sample size was limited, this treatment may prevent the emergence of EGFR secondary mutations that trigger drug resistance. Further studies are warranted to establish the significance of this treatment. CLINICAL TRIAL REGISTRATION: jRCTs051180009.

Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8+ T cell cytotoxicity and proliferation.

Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non-small cell lung cancer (NSCLC) responded significantly better to anti-programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8+ T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy.

Non-small cell lung cancer with tumor proportion score > 90% could increase the risk of severe immune-related adverse events in first-line treatments with immune checkpoint inhibitors: A retrospective single-center study.

BACKGROUND: Since 2015, immune checkpoint inhibitors have been a clinical treatment strategy for patients with advanced or recurrent non-small cell lung cancer (NSCLC). However, the relationship between immune-related adverse event (irAE) risk factors and patient clinical characteristics is unclear. This study aimed to evaluate the relationship between irAE risk and the clinical characteristics of patients with NSCLC. METHODS: We included patients with advanced or recurrent NSCLC with known programmed death-ligand 1 expression levels treated with immune checkpoint inhibitors. We retrospectively examined the medical records of 260 patients with NSCLC (March 2016-November 2020) and analyzed the relationship between the patient clinical characteristics and irAEs. RESULTS: Our retrospective analysis revealed that tumor proportion score (TPS) ≥ 90% and adenocarcinoma histology were independent risk factors for irAEs (odds ratio: 3.750 95% confidence interval [CI]: 1.58-8.89 and 0.424 95% CI: 0.19-0.97, respectively) in first-line treatment. However, in patients receiving second- or later-line treatments, no clinical characteristics were identified as risk factors for irAEs. Furthermore, no difference was observed in the response rates to first-line treatments between the TPS ≥ 90% and TPS < 90% groups (74% vs. 71%, p = 0.83). In later-line treatments, the TPS ≥ 90% group had a better response rate than the TPS < 90% group (55% vs. 17%, p < 0.05). However, no significant differences in overall survival were observed in either of the groups. CONCLUSIONS: TPS ≥ 90% and adenocarcinoma histology were independent risk factors for irAEs in previously untreated patients with advanced or recurrent NSCLC. Therefore, patients at high risk of irAEs require additional monitoring.

Peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer patients.

Anti-programmed cell death-1 (PD-1) therapy exerts beneficial effects in a limited population of cancer patients. Therefore, more accurate diagnostics to predict the efficacy of anti-PD-1 therapy are desired. The present study investigated whether peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer (NSCLC) patients. Advanced NSCLC patients treated with anti-PD-1 monotherapy (nivolumab or pembrolizumab) were consecutively enrolled in the present study. Peripheral blood samples were subjected to an analysis of peripheral T cell cytotoxicity and flow cytometry prior to the initiation of anti-PD-1 therapy. Peripheral T cell cytotoxicity was assessed using bispecific T-cell engager (BiTE) technology. We found that progression-free survival was significantly longer in patients with high peripheral T cell cytotoxicity (p = 0.0094). In the multivariate analysis, treatment line and peripheral T cell cytotoxicity were independent prognostic factors for progression-free survival. The analysis of T cell profiles revealed that peripheral T cell cytotoxicity correlated with the ratio of the effector memory population in CD4+ or CD8+ T cells. Furthermore, the results of flow cytometry showed that the peripheral CD45RA+CD25+/CD4+ T cell ratio was higher in patients with than in those without severe adverse events (p = 0.0076). These results indicated that the peripheral T cell cytotoxicity predicted the efficacy of anti-PD-1 therapy for advanced NSCLC patients.

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L).

INTRODUCTION: Alternation of osimertinib and afatinib is a potential approach to overcome osimertinib resistance and to allow complementation of drug efficacy without compromising safety in patients with epidermal growth factor receptor gene (EGFR)-mutated non-small cell lung cancer (NSCLC). METHODS: Treatment-naive patients with stage IV NSCLC harboring an activating EGFR mutation (L858R or exon-19 deletion) were enrolled. Alternating cycles of osimertinib at 80 mg/day for 8 weeks followed by afatinib at 20 mg/day for 8 weeks were administered. The primary end point was 12-month progression-free survival (PFS) probability. RESULTS: Forty-six patients were enrolled and treated with study therapy. The 12-month PFS probability was 70.2% (60% confidence interval [CI], 63.9-75.6%; 95% CI, 54.2-81.5%), which did not meet the primary end point. After a median follow-up time of 25.7 months, the median PFS was 21.3 months (95% CI, 16.3 months-not reached). The overall response rate was 69.6% (95% CI, 54.2-82.3%). The most common treatment-related adverse events (any grade or grade ≥ 3, respectively) were diarrhea (73.9%, 4.3%), rash acneiform (63.0%, 2.2%), and paronychia (52.2%, 0%). Five cases of pneumonitis, two of grade 2 and thres of grade 3, were apparent, all of which developed during osimertinib treatment. Exploratory evaluation of circulating tumor DNA suggested that coexisting TP53 mutations did not influence PFS for the alternating therapy. CONCLUSIONS: Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy.

A case of acute and severe thrombocytopenia due to readministration of rifampicin.

A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10(3) to 3 × 10(3)/µl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.

Bronchial ethanol injection therapy for airway obstruction in lung cancer patients.

Obstructive endobronchial tumours often cause decreased quality of life. Bronchial ethanol injection (BEI) therapy is considered an effective modality for airway dilatation or haemoptysis without specialist equipment. Here, we report experiences of two cases in which BEI therapy was effective for obstructive endobronchial tumours. In Case 1 with adenoid cystic carcinoma of the lung, BEI therapy and balloon dilatation were performed as treatment for the left main bronchus restenosis after metallic stent insertion. In Case 2 with squamous cell carcinoma of the lung, BEI therapy was performed after radiation therapy to the lesion that recurred in the entrance of the superior segment of the right lower lobe. Tumour progression was controlled with multiple BEI therapy. We consider BEI therapy useful because this procedure is easy to conduct, has low cost and can be done under particular conditions including post-tracheobronchial stent placement and post-radiation.

EGFR-mutant lung adenocarcinoma associated with antisynthetase syndrome successfully treated with osimertinib.

Here, we report a rare case involving a 66-year-old man with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and antisynthetase syndrome (ASS) treated with osimertinib. The patient presented with respiratory failure and bilateral pulmonary opacities; he was diagnosed with ASS accompanied by interstitial lung disease (ILD), consistent with paraneoplastic syndrome. After steroid pulse therapy, osimertinib was administered for lung adenocarcinoma without ILD exacerbation. Osimertinib could therefore be a treatment option for EGFR-mutant lung cancer with paraneoplastic ILD.

Expectoration of tonsillar metastasis of pulmonary pleomorphic carcinoma after pseudoprogression: A case report.

Pulmonary pleomorphic carcinoma is a rare malignant tumor that grows rapidly and has a poor prognosis. Although no effective treatments have so far been established, immune checkpoint inhibitors (ICIs) have shown clinical improvement in some cases of pleomorphic carcinoma. However, pseudoprogression is a major concern for treatment of this carcinoma using ICIs. Here, we report the case of a 61-year-old man who was diagnosed with large cell carcinoma of the lung with brain metastases. Systemic chemotherapy comprising carboplatin and pemetrexed was administered as a first-line therapy; however, disease progression was observed. A tonsillar lesion grew rapidly after the administration of nivolumab as a second-line therapy. Tracheostomy was planned to avoid suffocation, but the patient naturally expectorated the tumor. Pathological examination revealed that it was a palatine tonsillar metastasis of pulmonary pleomorphic carcinoma with infiltration of CD8+/CD4- lymphocytes and necrosis. The primary lesion expanded after nivolumab administration and shrank with no additional nivolumab administration. We therefore concluded that pseudoprogression caused expectoration of the tonsillar metastasis. Hence, ICIs can cause serious adverse events due to pseudoprogression.

Minimal influence of tocilizumab on IFN-gamma synthesis by tuberculosis antigens.

Interferon gamma (IFN-gamma) production is a critical step of antituberculosis (anti-TB) immune response. The purpose of this study was to determine the influences of biologics, including the interleukin (IL)-6 receptor-inhibitor tocilizumab (TCZ), and tumor necrosis factor (TNF) antagonists infliximab (INF) and etanercept (ETA), on Mycobacterium tuberculosis (MTB) antigen-induced IFN-gamma production. MTB antigen (ESAT-6 and CFP-10)-induced IFN-gamma-releasing assay was performed with or without addition of biologics (TCZ, ETA, and INF) using whole blood from patients with active TB. ETA and INF inhibited IFN-gamma production in a dose-dependent manner. In whole blood from TB patients, ESAT-6 stimulated significant production of IFN-gamma (1.30 +/- 1.95 IU/ml), and TCZ did not inhibit IFN-gamma production (1.56 +/- 1.88 IU/ml). IFN-gamma production by ESAT-6 was inhibited by ETA and INF (0.98 +/- 1.74, 0.75 +/- 1.66 IU/ml, respectively). CFP-10 stimulated significant production of IFN-gamma (1.46 +/- 1.60 IU/ml), and TCZ did not inhibit IFN-gamma production (1.51 +/- 1.77 IU/ml). IFN-gamma production by CFP-10 was inhibited by ETA and INF (0.91 +/- 0.99, 0.72 +/- 0.88 IU/ml, respectively). TCD did not inhibit MTB antigen-induced IFN-gamma production. As IFN-gamma production is important in antimycobacterial host defenses, the minimal influence of TCZ on IFN-gamma-releasing assay suggests a low risk of latent TB infection reactivation during tocilizumab therapy.

Radiographic change over 11 years in a patient with asbestos-related pleural disease.

Asbestos-related pulmonary conditions such as benign asbestos pleural effusion (BAPE) and diffuse pleural thickening (DPT) can develop after many years of asbestos exposure. These conditions cause progressing constrictive deficit in pulmonary function which may lead to respiratory failure and death. We report the case of a 72-year-old man with asbestos-related BAPE and DPT which developed approximately 40 years after occupational asbestos exposure, leading to chronic respiratory failure and death. We were able to observe his clinical course including computed tomography (CT) scan evaluation over 11 years. In addition to this observation, moderate asbestos body concentration was confirmed in autopsy-derived lung tissue. There are few case reports that showed radiographic course of asbestos-related pulmonary disorder initiated as BAPE, followed by unilateral DPT and later bilateral DPT that was histologically proven with asbestos body. We consider his clinical course is important in managing this disease, especially in early phase.

Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.

BACKGROUND: Pirfenidone is an antifibrotic agent that is potentially effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, no study has reported on its prophylactic value against chemotherapy-associated acute IPF exacerbations when combined with chemotherapy for non-small cell lung cancer (NSCLC). The present study assessed the safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy or immune checkpoint inhibitors (ICIs) in patients with IPF and NSCLC. METHODS: A total of 14 patients with IPF and NSCLC who received treatment from 2013 to 2019 were included. Patients were treated with pirfenidone combined with carboplatin and nanoparticle albumin-bound paclitaxel or S-1 as first-line chemotherapy. After confirming disease progression, patients received cytotoxic agents or ICIs, including nivolumab and pembrolizumab. Pirfenidone was continued regardless of chemotherapy changes. Overall survival (OS) and progression-free survival (PFS) for lung cancer and IPF were calculated. Moreover, the cumulative incidence of acute exacerbation of IPF (AE-IPF) within one year was evaluated. RESULTS: Median PFS for lung cancer was 110 days (95% confidence interval [CI]: 57-199 days), while the median OS was 362 days (95% CI: 220-526 days). Moreover, PFS for IPF was 447 days (95% CI: 286-indeterminate days), and the cumulative incidence of AE-IPF within one year was 18%. Notably, none of the patients developed AE-IPF associated with first-line chemotherapy. Among the included patients, four received ICIs, none of whom developed ICI-associated AE-IPF. CONCLUSIONS: The present study found that pirfenidone combined with carboplatin-based regimens or ICIs might be safe first-line chemotherapy for patients with IPF and NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: No patients with IPF and NSCLC who received pirfenidone in combination with first-line carboplatin-based chemotherapy or late-line ICIs developed acute IPF exacerbations. What this study adds Pirfenidone might have a prophylactic effect against chemotherapy-associated AE-IPF.

Continued administration of pembrolizumab for adenocarcinoma of the lung after the onset of fulminant type 1 diabetes mellitus as an immune-related adverse effect: A case report.

A 61-year-old woman with stage IVA lung adenocarcinoma exhibited high PD-L1 expression. Pembrolizumab was administered as second-line therapy. She developed destructive thyroiditis and her thyroid function started to decline during the administration of three to five courses. She was subsequently diagnosed with fulminant type 1 diabetes mellitus and ketoacidosis during the eighth course and insulin treatment was initiated. Pembrolizumab remained effective and was continued for 21 courses, even after the onset of diabetes mellitus. Immune-checkpoint inhibitor treatment can be continued with hormone replacement even after the development of type 1 diabetes mellitus as an immune-related adverse event.