Activity of afatinib in patients with NSCLC harboring novel uncommon mutations with or without co-mutations: a case report.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent first-line standard of care in unresectable mutation-positive (m+) non-small cell lung cancer (NSCLC). However, 10-20% of patients with m+ NSCLC have uncommon variants, defined as mutations other than L858R substitutions or exon 19 deletions. NSCLC harboring uncommon mutations may demonstrate lower sensitivity to targeted agents than NSCLC with L858R or exon 19 deletion mutations.

Older patients with EGFR mutation-positive non-small cell lung cancer treated with afatinib in clinical practice: A subset analysis of the non-interventional GIDEON study.

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.

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV.

Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI.

Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program.

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown.

Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021.

Afatinib as first-line treatment in patients with -mutated non-small cell lung cancer in routine clinical practice.

Background: Lung cancer is a leading cause of cancer-related death in Germany and worldwide. Non-small cell lung cancer (NSCLC) comprises ~80% of lung cancer diagnoses; in White patients, around 10% of NSCLC cases are epidermal growth factor receptor mutation-positive (m+). Head-to-head clinical trials have demonstrated superior efficacy with second-/third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first-generation EGFR TKIs in m+ NSCLC.

Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program.

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib.

Patients And Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed.

Results: In total, 52 patients were included [median age 57 years (range 32-81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively.

Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV.

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV.

Capmatinib in Exon 14-Mutated or -Amplified Non-Small-Cell Lung Cancer.

Background: Among patients with non-small-cell lung cancer (NSCLC), exon 14 skipping mutations occur in 3 to 4% and amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation.

Methods: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with -dysregulated advanced NSCLC.

Efficacy and safety analysis of the German expanded access program of osimertinib in patients with advanced, T790M-positive non-small cell lung cancer.

Purpose: Osimertinib, a third-generation irreversible mutant-selective inhibitor of EGFR kinase activity was clinically evaluated in the AURA trials, where it showed high clinical efficacy and a favorable toxicity profile in patients with acquired exon 20-EGFR pT790M mutation. We provide the clinical data of the German expanded access program that further characterizes the efficacy and safety of osimertinib in a heterogeneous patient population outside clinical trials.

Methods: We performed a retrospective data analysis on patients who were included into the German osimertinib EAP.

Corrigendum: Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

[This corrects the article on p. 449 in vol. 8, PMID: 28507545.

Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized.

Experience with afatinib in patients with non-small cell lung cancer progressing after clinical benefit from gefitinib and erlotinib.

Background: Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP).

PARAMOUNT: Descriptive subgroup analyses of final overall survival for the phase III study of maintenance pemetrexed versus placebo following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

Introduction: The PARAMOUNT phase III trial demonstrated that pemetrexed continuation maintenance significantly reduced the risk of disease progression (hazard ratio = 0.62) and death (hazard ratio = 0.78) versus placebo in patients with advanced nonsquamous non-small-cell lung cancer.

PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

Purpose: In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.

Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial.

Background: Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin.

Methods: In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated.

Everolimus in combination with pemetrexed in patients with advanced non-small cell lung cancer previously treated with chemotherapy: a phase I study using a novel, adaptive Bayesian dose-escalation model.

Introduction: Pemetrexed is an established second-line therapy for non-small cell lung cancer (NSCLC). Everolimus has previously been shown to have some clinical activity when used as a single agent in NSCLC. The aim of this phase I study was to evaluate the safety and feasibility of combining pemetrexed with everolimus in patients with NSCLC who had disease progression after one previous treatment.

Miliary never-smoking adenocarcinoma of the lung: strong association with epidermal growth factor receptor exon 19 deletion.

Miliary pattern of pulmonary metastases is a rarity in patients with lung cancer. We report five cases of patients with a never-smoking adenocarcinoma of the lung with such a pattern of metastases. In the tumor cells of all five patients, epidermal growth factor receptor (EGFR) mutation gene sequencing identified a deletion in exon 19 of the EGFR gene, and all five patients had a dramatic response to EGFR tyrosine kinase inhibitors.

Lessons learnt from gefitinib and erlotinib: Key insights into small-molecule EGFR-targeted kinase inhibitors in non-small cell lung cancer.

Improving treatment options and patient outcomes for those with non-small cell lung cancer (NSCLC) represents a significant worldwide challenge. Although traditional treatment strategies are widely accepted and initially successful, many tumors still fail to respond to available drugs. Therapeutic options for patients with NSCLC are therefore moving towards more individual and personalized treatment strategies.

Elevated pretreatment serum concentration of YKL-40-An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer.

Background: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL-40 has not been established in nonsmall cell lung cancer (NSCLC).

Single-center management of 136 patients with cancer of unknown primary site (CUP syndrome) over a period of 10 years.

Background: Cancer of unknown primary site (CUP syndrome) is a particular challenge in oncology which occurs in about 5-10% of cancer patients. Here, we investigated clinicopathological and prognostic factors in patients with CUP syndrome in a retrospective analysis.

Patients And Methods: 136 patients with CUP syndrome who were treated in our Department of Oncology and Hematology were analyzed over a period of 10 years.

Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study.

Background: Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance therapy in patients with this disease.

Methods: This randomised double-blind study was undertaken in 83 centres in 20 countries.

Expression of CEACAM-1 in pulmonary adenocarcinomas and their metastases.

Background: CEACAM-1 is involved in intercellular adhesion and is expressed in a variety of human tissues. In cases of malignant transformation, a down-regulation or loss of CEACAM-1 has been shown. In contrast, CEACAM-1 is not expressed in normal lung tissue or melanocytes.

Epidermal growth factor receptor-related tumor markers and clinical outcomes with erlotinib in non-small cell lung cancer: an analysis of patients from german centers in the TRUST study.

Introduction: Relationships between clinical outcomes and epidermal growth factor receptor (EGFR)-related tumor markers were investigated in patients with advanced non-small cell lung cancer.

Methods: Patients with stage IIIB/IV non-small cell lung cancer (0-2 prior regimens) received erlotinib (150 mg PO per day). Response and survival were evaluated, and tumor samples were assessed by immunohistochemistry (EGFR, phosphorylated mitogen-activated protein kinase, and phosphorylated AKT protein expression), fluorescence in situ hybridization (FISH; EGFR gene copy number), and DNA sequencing (EGFR, KRAS gene mutations).

A pilot study of docetaxel and trofosfamide as second-line 'metronomic' chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC).

Background: The aim of this pilot study was to evaluate the efficacy and safety of a chemotherapy containing docetaxel and oral trofosfamide as a 'metronomic' secondline treatment of patients with metastatic non-small cell lung cancer (NSCLC).

Patients And Methods: 21 patients with stage IV disease NSCLC who had progressed under first-line chemotherapy were enrolled. Previous chemotherapy was platinum-based in 15 patients (71.

Adjuvant chemotherapy after complete resection of non-small cell lung cancer.

Introduction: In non-small cell lung cancer (NSCLC) surgical resection is the treatment of choice in stages I and II of the disease; but even of this selected group of patients, almost half suffer recurrence following complete resection, usually in the form of distant metastases. The role of adjuvant systemic chemotherapy has been investigated extensively in the last two decades.

Methods: Selective literature review of randomized phase III trials.