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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.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.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.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.

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., We report a case of expectoration of tonsillar metastasis of pulmonary pleomorphic carcinoma after administration of nivolumab. We concluded that pseudoprogression caused expectoration of tonsillar metastasis, since the specimen of biopsy from tonsillar metastasis showed infiltration of CD8+/4‐ cells. This rare condition assists in elucidating the mechanism of pseudoprogression.

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., We report a case involving a patient with epidermal growth factor receptor‐mutant lung adenocarcinoma and antisynthetase syndrome accompanied by interstitial lung disease (ILD), treated with osimertinib. After steroid pulse therapy, osimertinib was administered for the lung adenocarcinoma, without ILD exacerbation. Osimertinib could be a treatment option for EGFR‐mutant lung cancer with paraneoplastic ILD.

Background Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is the standard treatment for advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations, such as exon 19 deletion or L858 point mutation. However, the effectiveness of EGFR-TKIs for patients with uncommon EGFR mutations remains unclear. Methods We retrospectively surveyed a consecutive database of NSCLC patients with EGFR mutations at five participating institutions. Data from NSCLC patients with uncommon mutations (including single or compound mutations), who were treated with systemic therapy between May 2016 and October 2018, were collected and analyzed. Results A total of 23 of the 524 patients whose data were collected had uncommon EGFR mutations. Of these, 22 received EGFR-TKIs (gefitinib = 6, erlotinib = 4, and afatinib = 12). Patients who received first EGFR-TKIs had overall response and disease control rates of 59.1% and 81.8%, respectively. The median progression-free survival (PFS) of patients with G719X mutation (n = 13, median PFS = 32.9 months) was favorable, compared with those of patients with L861Q mutation (n = 4, median PFS = 6.4 months) and compound mutations (n = 4, median PFS = 7.3 months). The PFS of patients who received first- and second-generation EGFR-TKIs was 14.0 months (n = 10) and 7.3 months (n = 12), respectively. The median cumulative duration of treatment (DOT) with EGFR-TKIs was 30.4 months, which was longer than those of cytotoxic chemotherapy (median DOT = 10.7 months) or immune checkpoint inhibitors (median DOT = 6.6 months). Conclusions EGFR-TKIs elicit favorable responses and contribute to long-term disease control in NSCLC patients with uncommon EGFR mutations. Key points Significant findings of the study: Our results demonstrate that both first- and second-generation EGFR-TKIs elicit favorable responses in NSCLC patients with uncommon EGFR mutations. What this study adds This study revealed all clinical courses for NSCLC patients with uncommon EGFR mutations. In addition to EGFR-TKIs, CCT and ICIs were found to contribute to long-term disease control in this cohort.

Background Epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) therapy is the standard treatment for advanced non‐small cell lung cancer (NSCLC) harboring common EGFR mutations, such as exon 19 deletion or L858 point mutation. However, the effectiveness of EGFR‐TKIs for patients with uncommon EGFR mutations remains unclear. Methods We retrospectively surveyed a consecutive database of NSCLC patients with EGFR mutations at five participating institutions. Data from NSCLC patients with uncommon mutations (including single or compound mutations), who were treated with systemic therapy between May 2016 and October 2018, were collected and analyzed. Results A total of 23 of the 524 patients whose data were collected had uncommon EGFR mutations. Of these, 22 received EGFR‐TKIs (gefitinib = 6, erlotinib = 4, and afatinib = 12). Patients who received first EGFR‐TKIs had overall response and disease control rates of 59.1% and 81.8%, respectively. The median progression‐free survival (PFS) of patients with G719X mutation (n = 13, median PFS = 32.9 months) was favorable, compared with those of patients with L861Q mutation (n = 4, median PFS = 6.4 months) and compound mutations (n = 4, median PFS = 7.3 months). The PFS of patients who received first‐ and second‐generation EGFR‐TKIs was 14.0 months (n = 10) and 7.3 months (n = 12), respectively. The median cumulative duration of treatment (DOT) with EGFR‐TKIs was 30.4 months, which was longer than those of cytotoxic chemotherapy (median DOT = 10.7 months) or immune checkpoint inhibitors (median DOT = 6.6 months). Conclusions EGFR‐TKIs elicit favorable responses and contribute to long‐term disease control in NSCLC patients with uncommon EGFR mutations. Key points Significant findings of the study: Our results demonstrate that both first‐ and second‐generation EGFR‐TKIs elicit favorable responses in NSCLC patients with uncommon EGFR mutations. What this study adds This study revealed all clinical courses for NSCLC patients with uncommon EGFR mutations. In addition to EGFR‐TKIs, CCT and ICIs were found to contribute to long‐term disease control in this cohort., This study revealed all clinical courses for NSCLC patients with uncommon EGFR mutations. In addition to EGFR‐TKIs, cytotoxic chemotherapy (CCT) and immune checkpoint inhibitors (ICIs) contributed to long‐term disease control in this cohort.

BACKGROUND Nivolumab is an anti-PD-1 blocking monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and worsening clinical status, known as hyperprogressive disease. We retrospectively reviewed the clinical records of patients with NSCLC administered nivolumab therapy at Toneyama National Hospital, Japan, from January 2016 to January 2018. Of the 87 patients administered nivolumab therapy, five experienced rapid progression during one cycle of nivolumab therapy. Four patients were treated with corticosteroids to overcome their symptomatic events. Nivolumab exhibited efficacy after temporal progression, so-called "pseudoprogression", in three patients, and their symptoms and laboratory results improved. In the other patient, pleural and pericardial effusions increased after nivolumab therapy, and drainage was required, with no subsequent recurrence. The clinical courses of our case series indicate that alternative treatment, namely high-dose corticosteroids, antibiotics, and drainage, effectively treated the symptoms of rapid tumor progression. Of note, corticosteroids suppressed the temporary inflammatory reaction to nivolumab. Although hyperprogressive disease is thought to be associated with poor quality of life and survival, these treatment strategies may be useful in patients with expected responses to immunotherapy.

Pleomorphic carcinoma (PC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59-year-old woman (Case 1), a 66-year-old man (Case 2), and an 83-year-old man (Case 3). PD-L1 was highly expressed in their tumor cells. Two cases showed a partial response with long progression-free survival. However, in Case 2, brain and bone metastases progressed during nivolumab treatment in spite of high PD-L1 expression. This case series indicates that nivolumab is effective to some extent for PC of the lung. However, the clinical course of patients treated with nivolumab should be carefully observed, even when PD-L1 is highly expressed.