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Purpose: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with non-small cell lung cancer harboring EGFR mutations. Although the frequency of osimertinib-induced interstitial lung disease (osi-ILD) is high, the optimal cancer treatment after osi-ILD has not been established. This time, we focused on the safety and efficacy of gefitinib following osi-ILD. Case Presentation: We experienced six cases (five women and one man; median age: 74 years) in which gefitinib was administered after osi-ILD. All six cases had grade 2 or higher osi-ILD and required steroid treatment. The computed tomography imaging pattern of osi-ILD revealed organizing pneumonia in three cases, diffuse alveolar damage in two cases, and hypersensitivity pneumonia in one case. Eastern Cooperative Oncology Group performance status was 1 in four cases, 2 in one case, and 3 in one case. EGFR mutation status was exon 19 deletion in two cases and exon 21 L858R in four cases. Only one patient experienced recurrence of ILD after receiving gefitinib. The best response to gefitinib was partial response in two cases and stable disease in three cases; one case was not evaluable. The median progression-free survival after treatment with gefitinib was 190 days (95% confidence interval: 33– 328). Conclusion: The treatment with gefitinib after the development of osi-ILD was safe and effective. Gefitinib may be a promising option for patients who recovered from severe osi-ILD. [ABSTRACT FROM AUTHOR]

Background: Rechallenge with platinum‐combination chemotherapy in patients with advanced non‐small cell lung cancer (NSCLC) after disease progression on platinum‐combination chemotherapy occasionally leads to a favorable response. The efficacy and safety of platinum‐combination chemotherapy with or without immune‐checkpoint inhibitor (ICI) for patients with recurrent NSCLC after surgery followed by adjuvant platinum‐doublet chemotherapy remains uncertain. Methods: Patients who relapsed after surgery plus adjuvant platinum‐doublet chemotherapy and received platinum‐combination chemotherapy with or without ICI between April 2011 and March 2021 at four Nippon Medical School hospitals were retrospectively analyzed. Results: Among 177 patients who received adjuvant platinum‐doublet chemotherapy after surgery, a total of 30 patients who received platinum‐combination rechemotherapy with or without ICI after relapse were included in this study. Seven patients received ICI‐combined chemotherapy. The median disease‐free survival (DFS) after surgery was 13.6 months. The objective response rate and disease‐control rate were 46.7% and 80.0%, respectively. The median progression‐free survival and overall survival were 10.2 and 37.5 months, respectively. Patients with longer DFS (≥12 months) had a better prognosis than others. The most common grade ≥3 toxicity associated with this treatment was neutropenia (33%). Grade ≥3 immune‐related adverse events were pneumonitis (14%) and colitis (14%). Treatment‐related deaths did not occur in this study. Conclusion: Platinum‐combination chemotherapy with or without ICI for patients with postoperative recurrent NSCLC who previously received adjuvant platinum‐doublet chemotherapy was effective and safe. In particular, this therapy may be promising for patients with longer DFS. [ABSTRACT FROM AUTHOR]

Background: Osimertinib is a third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) approved for the treatment of patients with EGFR‐mutant non‐small cell lung cancer (NSCLC). However, the mechanisms of acquired drug resistance to osimertinib have not as yet been clarified. Exosomes and microRNAs (miRNAs) are involved in carcinogenesis and drug resistance in human cancers. Methods: We used previously established osimertinib‐resistant HCC827 (HCC827‐OR) and PC‐9 (PC‐9‐OR) cells. We evaluated the profiles of exosomal miRNA associated with resistance to osimertinib in EGFR‐mutant NSCLC cells. Results: Epithelial–mesenchymal transition (EMT) phenomenon was observed in HCC827‐OR and PC‐9‐OR cells. Microarray and quantitative reverse transcription‐polymerase chain reaction analysis revealed that miR‐210‐3p was co‐upregulated in exosomes isolated from HCC827‐OR and PC‐9‐OR cells compared with those isolated from parental HCC827 and PC‐9 cells. HCC827‐OR cell‐derived exosomes induced EMT changes and resistance to osimertinib in HCC827 cells. Subsequently, the induction of miR‐210‐3p directly promoted the EMT phenomenon and resistance to osimertinib in HCC827 cells. Conclusions: Exosomal miR‐210‐3p may play a crucial role in resistance to osimertinib in the tumor microenvironment of EGFR‐mutant NSCLC. [ABSTRACT FROM AUTHOR]

Background: The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients., Methods: This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay., Results: Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor ( EGFR ) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common EGFR mutations than the other histologic patterns (50.6% vs. 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03)., Conclusions: Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-506/coif). L.S., H.D. and S.C. are employees of Burning Rock Biotech, Guangzhou, China. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE., Methods: We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated., Results: Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death., Conclusions: The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-347/coif). K.H. reports personal fees from AstraZeneca, MSD, Kyorin Pharmaceutical, Chugai Pharmaceutical, and Daiichi-Sankyo, outside the submitted work. M.S. reports grants from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Kayaku, and Kyowa Hakko Kirin; and personal fees from AstraZeneca, MSD, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo, Merck Biopharma, and Amgen, outside the submitted work. T.H. reports grants from Chugai Pharmaceutical, Nippon Boehringer Ingelheim, and Taiho Pharmaceutical; and personal fees from Chugai Pharmaceutical, AstraZeneca, MSD, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Eli Lilly, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda Pharmaceutical, Pfizer, and Novartis, outside the submitted work. The other author has no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objectives: Patients with lung cancer and interstitial lung disease (ILD), usual interstitial pneumonia in particular, are known to have a poor outcome. The aim of this study was to evaluate the prognostic impact of ILD in patients with non-small-cell lung cancer., Methods: A total of 2054 consecutive patients underwent complete resection of Stage IA-IIIA non-small-cell lung cancer in our institution between January 2002 and March 2013. The presence of ILD was diagnosed and categorized based on high-resolution computed tomography images. Multivariate analysis was performed to identify the prognostic factors., Results: There were 106 (5%) patients with ILD. There were significantly more patients who developed severe complications (P < 0.01) in the ILD group, with 4 (4%) patients developing acute exacerbation. Although the difference in postoperative mortality rate was marginal between the groups (P = 0.07), the 5-year overall survival and cancer-specific survival rates of the ILD patients were significantly worse than those of the non-ILD group (overall survival: 40.4% vs 72.0%, P < 0.01; cancer-specific survival 55.4% vs 78.6%, P < 0.01). The results of multivariate analysis showed that coexistence of ILD (hazard ratio 1.45; P = 0.01) was an independent, unfavourable prognostic factor., Conclusions: The presence of ILD led to a much poorer survival after complete resection of non-small-cell lung cancer.