Pembrolizumab-Induced Delayed-Onset Hepatitis.

Hepatitis is one of the serious immune-related adverse events (irAEs). However, delayed-onset hepatitis induced by immune-checkpoint inhibitors (ICIs) is rare, and the histopathological features remain to be clarified. A 65-year-old woman with advanced lung adenocarcinoma in the right upper lobe (cT4N3M1c, c-stage IVB) received four courses of pembrolizumab. Her hepatic and biliary tract enzyme levels started increasing 2 months after the final administration of pembrolizumab, and the elevated levels of these enzymes prolonged. Liver biopsy revealed panlobular infiltration of inflammatory cells, and most of the infiltrating inflammatory cells were lymphocytes; however, there were a small number of neutrophils, eosinophils, and plasma cells. There was no confluent necrosis. Furthermore, immunohistochemical analyses proved that infiltrating lymphocytes were predominantly CD3-positive (CD3+) and CD8+, and few CD20+ and CD4+ lymphocytes were observed. Based on these findings, she was diagnosed with a case of hepatitis as an irAE. Administration of prednisolone (0.5 mg/kg/day) as well as the addition of azathioprine failed to suppress the deterioration. However, an increase in the dose of prednisolone (up to 1 mg/kg/day) enabled us to control hepatitis. This case showed that hepatitis can occur even after discontinuation of ICIs, and that liver biopsy may be useful in the diagnosis. Clinicians should not hesitate to perform liver biopsy for confirmation of the diagnosis.

Which Is Better EGFR-TKI Followed by Osimertinib: Afatinib or Gefitinib/Erlotinib?

BACKGROUND/AIM: Treatment with EGFR-tyrosine kinase inhibitor (TKI) shows a durable response against NSCLC harboring EGFR mutation; however, treatment resistance occurs within 1-1.5 years following first-line EGFR-TKIs [first- and second-generation (G) TKIs]. When resistant NSCLC exhibits T790M mutations, osimertinib is the standard therapy. However, intratumoral heterogeneity and clonal evolution may occur in NSCLC. Afatinib may overcome tumor heterogeneity, leading to T790M colonal purity. We aimed to determine whether NSCLC treatment with afatinib followed by osimertinib (afatinib group) provides higher therapeutic efficacy than other 1st-G EFGR-TKIs followed by osimertinib (1st-G group). MATERIALS AND METHODS: This multicenter retrospective study evaluated outcomes between afatinib group and 1st-G group. We analyzed clinical data from NSCLC patients receiving osimertinib after progression following 1st- or 2nd-G EGFR-TKIs between March 28, 2016 and March 31, 2018. Patients with performance status (PS) 0-2 were enrolled to reduce bias of patients' conditions. RESULTS: We enrolled 111 patients treated with osimertinib. The median age was 69 (range: 39-88) years. Out of 111 patients, 33 (29.7%) were men, 100 (90%) had PS 0-1, and 35 (31.5%) were in the afatinib group. The objective RR and DCR were significantly higher in the afatinib group than in the 1st-G group [82.9% vs. 53.9% (p=0.0065); 91.4% vs. 71.1% (p=0.032)]. The median PFS tended higher in the afatinib group than in the 1st-G group (15.6 vs. 8.9 months, p=0.195). CONCLUSION: Afatinib followed by osimertinib may provide better outcomes for T790M-positive NSCLC than 1st-G EGFR-TKIs. Afatinib followed by osimertinib may be a therapeutic option for NSCLC harboring EGFR mutation.

Re-challenge chemotherapy in patients with sensitive relapse small-cell lung cancer and interstitial lung disease.

BACKGROUND: Treatment modalities for small-cell lung cancer (SCLC) with pre-existing interstitial lung disease (ILD) are limited. Although re-challenge with first-line chemotherapy can be effective for sensitive relapse SCLC, its safety and efficacy are uncertain in cases with ILD. This study aimed to investigate both the efficacy and safety of re-challenge chemotherapy in patients with sensitive relapse SCLC with ILD. METHODS: Patients with sensitive relapse SCLC with ILD who received re-challenge chemotherapy were studied retrospectively. Sensitive relapse was defined as a treatment-free interval (TFI) of more than 60 days after first-line platinum-based treatment. The endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Re-challenge platinum and etoposide were administered in 11 patients, with the median re-challenge cycle of 3. The overall response rate was 55%. The median PFS and OS from the time of re-challenge treatment were 4 months (95% CI, 2.9-NA) and 9.2 months (95% CI, 8.0-NA), respectively. One patient developed acute exacerbation of ILD 173 days after the last course of re-challenge treatment. CONCLUSIONS: Re-challenge chemotherapy can be effective and considered in SCLC patients with pre-existing ILD.