We analysed patients with advanced non-small cell lung cancer (NSCLC) who were treated with immune-checkpoint inhibitors (ICIs) to address the effect of the timeline and reason for corticosteroid administration on survival outcomes. We retrospectively collected clinical data of non-oncogenic driven, advanced NSCLC patients treated with ICIs at Karolinska University Hospital, including the timeline and reason for steroid administration. Steroid administration was defined as > 10 mg prednisolone equivalent for ≥10 days. We subcategorized patients based on the aetiology of steroid administration into three subgroups: a) steroids for supportive reasons but not for cancer palliation; b) steroids for the palliation of cancer-related symptoms; c) steroids for the management of immune-related adverse events (irAEs). Furthermore, to analyse the timeline, patients were categorised into two groups; those who received corticosteroids within 2 weeks before until 2 days after ICI initiation and those who received steroids later during their treatment course. Analysed data from 196 patients showed 46.3% of patients received corticosteroids. Steroid administration due to irAEs did not affect overall survival (OS) (p = 0.38) compared with the steroid naïve group. Only steroid administration for the palliation of cancer-related symptoms was an independent predictor for shorter OS (HR = 2.7; 95% CI, 1.5-4.9). The timeline of steroid administration did not affect OS (p = 0.456) in our cohort. Steroids due to irAEs do not appear to hamper ICI efficacy. However, the administration of high-dose steroids to palliate malignancy-associated symptoms might reflect the dismal prognosis of this patient group.

The emergence of tyrosine kinase inhibitors and immune checkpoint inhibitors has paved a new era for the management of non‐small cell lung cancer, which has for many years lacked major clinical breakthroughs. Historically, 5‐year overall survival remained below 5% in individuals with metastatic disease. These novel treatments have led to significant prolongation of survival in the locally advanced and metastatic setting, exceeding 25% in selected populations. However, they present new challenges to clinicians due to their inherently different spectrum of toxicity unique to each specific drug's pharmacodynamic profile. Internists commonly come across these side effects in their daily clinical practice. Their optimal recognition and management are of utmost importance, because it is associated with significant improvements in patient survival outcomes and their quality of life. The aim of this review is to summarize the complications following these novel treatments for non–small cell lung cancer.

There is lack of data addressing the intracranial (IC) efficacy of immune checkpoint inhibitors (ICIs) on brain metastases (BM) in non-small cell lung cancer (NSCLC). This patient category is underrepresented in randomized clinical trials. We retrospectively collected clinical data on patients with non-oncogenic driven NSCLC with BM who were treated with ICIs at two medical oncology institutes in Sweden and Greece from 2016 to 2019. IC efficacy was assessed in patients who had not received local treatment for BM less than three months prior to the initiation of ICIs and had adequate radiological evaluation. We screened 280 patients, of which 51 had BM. BM was an independent predictor for inferior PFS (HR = 2.27; 95% CI, 1.53–3.36) but not OS (HR = 1.58; 95% CI, 0.97–2.60) for the whole patient population. IC response assessment was done on 33 patients. IC objective response rate (ORR) was 24.2%. The presence of neurological symptoms related to BM did not affect IC ORR (p = 0.48). High PD-L1 levels from extracranial biopsies were not a predictive factor for IC ORR (p = 0.13). ICIs are active in NSCLC patients with BM regardless of the presence of neurological symptoms and can achieve durable IC disease stabilization in a subgroup of patients.

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

Asian patients with metastatic non-small cell lung cancer (NSCLC) have a higher prevalence of epidermal growth factor receptor (EGFR) mutations compared to Caucasians, 30-50% and 15%, respectively. Osimertinib is a tyrosine kinase inhibitor approved as first-line therapy in patients with metastatic NSCLC harboring exon 19 or exon 21 EGFR mutations. We report a 68-year-old treatment-naïve Asian male patient with metastatic NSCLC harboring an exon 19 deletion mutation of EGFR treated with osimertinib. The patient developed an osimertinib-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after approximately two months of therapy. Following fluid restriction and osimertinib discontinuation, the hyponatremia improved significantly within one week. The patient was started on second-line erlotinib without any signs of hyponatremia after treatment initiation. There is a lack of published data from randomized prospective clinical trials of osimertinib-induced SIADH in metastatic NSCLC. Further studies to evaluate the potential underlying mechanisms are warranted.