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Introduction: Lung cancer is most common in older patients; despite this, older patients are historically under-represented in clinical studies. Here we present data from GIDEON, a study undertaken in Germany in patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) receiving first-line afatinib. GIDEON enrolled a high proportion of patients aged ≥70 years, providing an opportunity to study afatinib use in older patients., Materials and Methods: In GIDEON (NCT02047903), a prospective non-interventional study, patients with EGFRm+ NSCLC received first-line afatinib in routine clinical practice until disease progression, death or intolerable adverse events. Key objectives were twelve-month progression-free survival (PFS) rate and objective response rate (ORR). Overall survival (OS) and safety were also assessed. This post hoc analysis explores outcomes of patients grouped by age (≥70 and <70 years)., Results: In the 152 patients enrolled in GIDEON (69.7% female, 64.5%/22.4%/13.2% with Del19/L858R/other exon 18-21 mutations, 33.6% with brain metastases), the median age was 67 years (range 38-89) and 43.4% were aged ≥70 years. In the ≥70 years age group and the <70 years age group, twelve-month PFS rate was 58.9% and 43.9%, median PFS was 17.2 months and 10.6 months, ORR was 72.0% and 76.5%, twelve-month OS rate was 79.1% and 79.2%, 24-month OS rate was 52.0% and 61.7%, and median OS was 30.4 months and 27.4 months, respectively. In the ≥70 years age group and the <70 years age group, grade ≥3 adverse drug reactions (ADRs) were observed in 34.8% and 40.7% of patients, respectively; the most common were diarrhea (13.6% and 14.0%), acneiform dermatitis (7.6% and 7.0%), stomatitis (1.5% and 4.7%) and maculopapular rash (1.5% and 4.7%)., Discussion: Patients with EGFRm+ NSCLC aged ≥70 years showed clinical benefit from first-line afatinib with no unexpected safety signals, supporting the use of afatinib in this setting., Competing Interests: Declaration of Competing Interest Wolfgang M. Brueckl reports receiving lecture and educational event (personal) fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Pfizer, Roche Pharmaceuticals, and Takeda; receiving congress (personal) fees from Boehringer Ingelheim, AstraZeneca, and Roche Pharmaceuticals; and receiving advisory board fees (personal) from AstraZeneca, Boehringer Ingelheim, Novartis, Merck Sharp & Dohme, Lilly Pharma, Bristol Myers Squibb, and Roche. Martin Reck reports serving on advisory councils or committees and receiving consulting fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Sanofi; and receiving speaker honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Kai Neben reports receiving honoraria (personal fees) from Roche, Takeda, Amgen, Janssen, Pfizer, Bayer, Merck Sharp & Dohme, Bristol Myers Squibb, and Chugai. Frank Griesinger reports receiving support for scientific research from ASTRA, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, GlaxoSmithKline, and Janssen; receiving honoraria for presentations from ASTRA, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Ariad, Abbvie, Siemens, Amgen, GlaxoSmithKline, Janssen, and Sanofi; and advisory board participation for ASTRA, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Ariad, Abbvie, Siemens, GlaxoSmithKline, Janssen, and Sanofi. Justyna Rawluk reports serving on advisory councils or committees for AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, and Takeda; and receiving consulting fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, and Takeda. Stefan Krüger reports receiving honoraria and grants or funds from Boehringer Ingelheim. Joachim H. Ficker reports receiving speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Aventis, and Bristol Myers Squibb. Miriam Möller reports receiving consulting fees (consulting or advisory role) from Boehringer Ingelheim and Roche; and receiving payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Boehringer Ingelheim, Roche, AstraZeneca, and Merck Sharp & Dohme. Andrea Schueler is an employee of Boehringer Ingelheim Pharma GmbH & Co KG. Eckart Laack, Konrad Kokowski and Harald Schäfer report no potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immune checkpoint inhibitors (ICI) either alone or in combination with chemotherapy have expanded our choice of agents for the palliative treatment of non-small cell lung cancer (NSCLC) patients. Unfortunately, not all patients will experience favorable response to treatment with ICI and may even suffer from severe side effects. Therefore, prognostic and predictive markers, beyond programmed death ligand 1 (PD-L1) expression status, are of utmost importance for decision making in the palliative treatment. This review focuses on clinical, laboratory and genetic markers, most of them easily to obtain in the daily clinical practice., Results: Recently, a number of prognostic and predictive factors in association to palliative ICI therapy have been described in NSCLC. Besides biometric parameters and clinical characteristics of the tumor, there are useful markers from routine blood sampling as well as innovative soluble genetic markers which can be determined before and during ICI treatment. Additionally, the level of evidence is noted., Conclusions: These factors can be helpful to predict patients' outcome and tumor response to ICI. They should be implemented prospectively in ICI based clinical trials to develop reliable algorithms for palliative NSCLC treatment.

Background: In this prospective non-interventional study, the effectiveness and tolerability of erlotinib in elderly patients with non-small-cell lung cancer (NSCLC) after ≥1 platinum-based chemotherapy were assessed., Methods: A total of 385 patients ≥65 years of age with advanced NSCLC receiving erlotinib were observed over 12 months. The primary endpoint was the 1-year overall survival (OS) rate., Results: Patients were predominantly Caucasian (99.2%), a mean of 73 years old; 24.7% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Most common tumor histologies were adenocarcinoma (64.9%) and squamous cell carcinoma (22.3%). Of 119 patients tested, 15.1% had an activating epidermal growth factor receptor gene (EGFR) mutation. The 1-year OS rate was 31% (95% CI 25-36) with a median OS of 7.1 months (95% CI 6.0-7.9). OS was significantly better in females than males (p = 0.0258) and in patients with an EGFR mutation compared to EGFR wild-type patients (p = 0.0004). OS was not affected by age (p = 0.3436) and ECOG PS (p = 0.5364). Patients with squamous NSCLC tended to live longer than patients with non-squamous EGFR wild-type tumors (median OS: 8.6 vs 5.5 months). Cough and dyspnea improved during the observation period. The erlotinib safety profile was comparable to that in previous studies with rash (45.2%) and diarrhea (22.6%) being the most frequently reported adverse events., Conclusions: Erlotinib represents a suitable palliative treatment option in further therapy lines for elderly patients with advanced NSCLC. The results obtained under real-life conditions add to our understanding of the benefits and risks of erlotinib in routine clinical practice., Trial Registration: BfArM ( https://www.bfarm.de ; ML23023); ClinicalTrials.gov (NCT01535729; 20 Feb 2012).

Background: Lung cancer can be described by histological subtype, of which small cell, squamous cell and adenocarcinoma are the most common. International data show that adenocarcinoma is becoming the dominant histological subtype of lung cancer although the relative risk due to smoking has been found to be smaller than that for other histological subtypes., Objective: The aim of the analysis was to describe the time trends in incidence of lung cancer among women and men in Germany according to histological subtype., Materials and Methods: All lung cancer cases (ICD-10 C33-C34) newly diagnosed between 2003 and 2012 and collected by the epidemiologic cancer registries of the German federal states with average completeness of registration of at least 90% were considered and grouped into histologic subtypes. If data on tumor histology were not microscopically verified or unspecific, multiple imputation techniques were applied to estimate the histologic subtype., Results: Among women age-standardized lung cancer rates increased considerably between 2003 and 2012 (annual percent change APC = 2.7%), mostly driven by a rising adenocarcinoma incidence (APC = 4.7%). Among men overall lung cancer rates decreased during the same time (APC = -1.7%). Still, a slight increase in adenocarcinoma incidence was also observed in men (APC = 1.0%)., Conclusion: The rising incidence of adenocarcinoma of the lung is alarming. The cancer registry data do not allow risk factor analysis. In the international discussion, the introduction of filter cigarettes as well as the changing composition of cigarettes has been hypothesized as being responsible. Further epidemiologic studies are strongly needed.

Background: Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has become important since the development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut-offs have been used in different trials to predict response to these drugs, thus comparison of those studies is difficult. We compared PD-L1 mRNA expression measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we investigated the impact of different tumour tissue acquisition methods on the reliability of PD-L1 measurement techniques., Materials and Methods: NSCLC cases (N=22), including n=9 mediastinal lymph node biopsies acquired by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and n=5 metastases, were evaluated prospectively for PD-L1 protein on tumor cells (TC) and immune cells (IC) using E1L3N and 28-8 antibodies and PD-L1 mRNA using the CheckPoint TYPER® assay., Results: In primary NSCLC tissues, agreement between PD-L1 mRNA and TC staining using the 28-8 antibody was excellent (ĸ=0.85, p=0.0002). Comparing both PD-L1 antibodies against each other showed a kappa value of 0.58 (p=0.0106). In EBUS-TBNA, PD-L1 mRNA correlated perfectly with the 28-8 antibody (ĸ=1.0, p=0.0023). PD-L1 mRNA levels significantly differed when comparing 28-8 TC staining of tumours >49% with 1-49% and 0% (p=0.0040; p=0.0081, respectively). In metastatic lesions, differences between PD-L1 mRNA and IHC became apparent (ĸ=0.2, p=0.2525)., Conclusion: Testing of PD-L1 mRNA and 28-8 IHC showed an excellent agreement in NSCLC samples including mediastinal lymph node biopsies. Since PD-L1 expression in >50% TC detected by 28-8 IHC can be reliably detected by RT-qPCR, quantitative PD-L1 mRNA determination should be considered as an alternative to IHC as there is no interobserver variability in RNA results., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Afatinib is a tyrosine kinase inhibitor (TKI), that has been approved for treating patients with epidermal growth factor receptor (EGFR) mutated advanced non-small-cell lung cancer (NSCLC). Stevens-Johnson syndrome (SJS) related to EGFR directed TKIs is a rare adverse event., Case Presentation: We report a case of a 79-year-old white female with EGFR-mutated, metastatic non-small-cell lung cancer treated with afatinib as first-line palliative treatment, who developed a SJS after two months of treatment. Discontinuation of the TKI and systemic glucocorticoid treatment led to improvement of symptoms and recovery., Conclusion: Severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes during treatment with afatinib should alert clinicians to suspect SJS and react appropriately., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)