No abstract

Background: First-line chemoimmunotherapy (CIT) has improved overall survival (OS) and progression-free survival (PFS) outcomes among patients with non-small cell lung cancer (NSCLC). The immunological and nutritional statuses of patients fluctuate during treatment using immune checkpoint inhibitors, and are closely related to treatment outcomes. However, it is unclear whether these markers are significant in patients who are receiving CIT. Methods: This retrospective single-center study evaluated 34 consecutive Japanese patients with NSCLC who were treated using first-line CIT. Previously reported markers that reflect immunological and nutritional statuses were evaluated at three time points: at the start of CIT, after three weeks, and at the end of induction therapy. Results: The median PFS was 7.2 months (95% confidence interval: 6.3 monthsnot reached) and the median OS was not reached (95% confidence interval: 9.6 months-not reached). The PFS duration was significantly associated with the baseline neutrophil-to-lymphocyte ratio and the three-week values for the modified Glasgow prognostic score, C-reactive protein-albumin ratio, prognostic nutrition index, and advanced lung cancer inflammation index. The OS duration was significantly associated with the pre-treatment values for the neutrophil-tolymphocyte ratio and advanced lung cancer inflammation index, as well as the prognostic nutrition index at the end of induction therapy. Conclusions: Immunological and nutritional markers could be useful for predicting the outcomes of CIT for Japanese patients with advanced non-small cell lung cancer. The timing of their evaluation may also be important.

The efficacy of nintedanib treatment in patients with idiopathic pulmonary fibrosis (IPF) was demonstrated in phase III trials. However, there is limited data on the significance of nintedanib in elderly patients aged ≥75 years. We have retrospectively evaluated 54 newly nintedanib-treated patients including 32 elderly individuals. Potential changes in modified medical research council (mMRC) grade and COPD (chronic obstructive pulmonary disease) assessment test (CAT) score, as well as in forced vital capacity (FVC) were obtained 6 months before, at the time of, and 6 and 12 months after initiation of nintedanib treatment. Significant differences were observed in CAT scores between 6 months before treatment and baseline (p < 0.001), and between baseline and 6 months (p < 0.001) and 12 months (p < 0.001) after treatment. If subjective improvement is defined as an improvement in mMRC grade or CAT score by 1 or 3 points, respectively, 25 patients (46.3%) have significantly improved after 6 months of treatment. Out of these, all have improved in CAT score. The tolerability of nintedanib was similar in elderly and younger patients. These findings suggest that CAT scores could be useful in the subjective assessment during nintedanib treatment, and that nintedanib is safe and efficient for the treatment of the elderly population.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening dermatologic adverse events in the same category, caused by a delayed-type drug hypersensitivity reaction. Although skin toxicity is common during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib-associated TEN is quite rare—thus far, only one report has been published from China. We report a case of an 80-year-old Japanese woman with lung adenocarcinoma harboring an EGFR-sensitizing mutation who was treated with osimertinib as the first-line treatment. Forty-six days after osimertinib induction, diffuse erythematous rash rapidly spread over the patient’s trunk along with vesicles and purpuric macules; furthermore, she developed targetoid erythema on the face. Despite osimertinib discontinuation and corticosteroid treatment, diffuse erythema with Nikolsky’s sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face. Based on her symptoms, TEN was diagnosed and thus, intravenous immunoglobulin was immediately administered for 4 days. The treatment ameliorated TEN-associated skin toxicity and caused epithelialization. Reports on osimertinib-associated SJS/TEN are scarce and only one report each on SJS and TEN from China is available. This is the first report of osimertinib-associated TEN from Japan. Cases of EGFR-TKI-associated SJS/TEN have been reported predominantly from Asian countries, suggesting ethnicity and genetic linkage play a role in the underlying mechanism.

Vogt–Koyanagi–Harada disease (VKHD) is a rare systemic granulomatous autoimmune disease that affects melanocyte‐rich organs such as eye, inner ear, meninges, skin, and hair. VKHD leads to chronic uveal inflammation accompanied by a decline in visual acuity in some patients when appropriate corticosteroid treatment was not initiated in an early phase. Immune checkpoint inhibitors (ICIs) are widely used in the treatment of several kinds of cancers and chemoimmunotherapy has become the standard of care in the first‐line treatment of non‐small cell lung cancer (NSCLC). While ICIs induce immune‐related adverse events, drug‐induced VKHD is quite rare with only four reports in the ICI monotherapy; three patients with melanoma and one patient with NSCLC. We describe the first case of VKHD during chemoimmunotherapy including pembrolizumab in a patient with NSCLC, which was successfully treated with corticosteroid without any sequela.