Comparison of PD-L1 expression between paired cytologic and histologic specimens from non-small cell lung cancer patients.

Expression of programmed death ligand 1 assessed on histologic samples is a confirmed predictive biomarker for anti-PD-1 immunotherapy, but its evaluation is not approved for immunocytochemistry. We investigated if PD-L1 expression shows comparable results on paired cytologic and histologic tumor specimens and interobserver variability. Percentage of PD-L1-positive tumor cells of 247 paired samples of non-small cell lung cancer was evaluated by three independent investigators. Samples were compared on the basis of the continuous values and also categorized with the tumor proportion score (TPS). Concordance was defined if continuous values were both within a deviation of 10% and if categorized values were identically grouped. Interobserver variability was assessed by the standard deviation of the mean. Based on continuous values between paired samples, perfect concordance rate was approximately 53%. With categorization of PD-L1 expression based on TPS, category was identical in 74.1%. However, defining the continuous values of PD-L1 expression between paired samples within a deviation of 10% as concordant, concordance rate was 82%. Interobserver variability was significantly higher in evaluation of cytologic specimens. Evaluation of PD-L1 expression in paired histologic and cytologic tumor specimens shows comparable results if a deviation of 10% between the values is tolerated. Interobserver variability demonstrates a much more challenging interpretation of PD-L1 expression for cytologic samples.

[Rebiopsy for Patients with Lung Cancer - Joint Opinion from both the Endoscopic and Thoracic Oncology Sections of the German Society of Pneumology (DGP)]. / Empfehlung der Sektionen 2 und 11 der DGP zur Rebiopsie bei Lungenkarzinomen.

Performing rebiopsies for primary lung cancer and/or their metastases is becoming more and more prominent in daily practice, as the therapeutical spectrum increases and some newer strategies are dependent on immunohistochemical and/or molecular factors. In general, nearly all recurrent lesions or metastases can be reached. However, frequently invasive procedures are necessary with the need to carefully weigh risks and benefits of rebiopsies for the patient in each case. In this review indications for recurrent and progressive disease as well as risks are discussed and alternatives to rebiopsies are shown. This work is the joint opinion from both the endoscopic and thoracic oncology sections of the German Society of Pneumology (DGP).

[Lung cancer : What has been confirmed in therapy?] / Lungenkarzinom : Was ist gesichert in der Therapie?

Metastatic non-small cell lung cancer has now been subdivided into several subtypes. The five basic principles of treatment include chemotherapy, anti-angiogenic therapy, targeted therapy, immunotherapy and early palliative care. The latter should be implemented for all patients with metastatic lung cancer. The use of the other modalities depends on the histological subtype, as well as on the immunohistochemical and molecular features of the tumor.

[Targeted therapy and precision medicine : More than just words in the treatment of lung cancer]. / Targeted Therapy und Precision Medicine : Mehr als nur Schlagworte in der Therapie von Lungenkarzinomen.

Between 10 and 15 % of non-small cell lung cancers (NSCLC) proliferate due to the presence of a so-called driver mutation. This molecular alteration allows the cancer to continue to proliferate and can be deliberately inhibited. In addition to mutations in the epidermal growth factor receptor gene (EGFR) and translocations between the echinoderm microtubule-associated protein-like 4 gene (EML 4) and the anaplastic lymphoma kinase gene (ALK), this applies to ROS1 gene translocations. For the former two alterations, many inhibitors are already available, whereas for ROS1 and other driving mutations the evidence is sparse due to the rare occurrence of these mutations in NSCLC.

[A reduced TKI dosage is not associated with loss of activity in EGFR mutated NSCLC patients]. / Reduzierte Dosis von TKI führt nicht zu Wirkungsverlust bei Patienten mit aktivierender EGFR-Mutation.

BACKGROUND: Patients treated with anti-EGFR tyrosine kinase inhibitors (TKI) may receive dose reduction due to toxicity; however, the impact on treatment efficacy and patient outcome remains unknown. PATIENTS AND METHODS: Patients with stage IV NSCLC harbouring EGFR mutations and treated at our institution were retrospectively analyzed for treatment with TKI in 2012 or later. RESULTS: Thirty patients with EGFR mutated adenocarcinoma were identified meeting the inclusion criteria. Eleven patients received cytotoxic therapy as first line treatment yielding in a response rate of 36 %. All patients were treated with TKI as first or second-line therapy which resulted in disease stabilization (23 %) or response (77 %) in all patients. The median progression-free survival was 21.4 months with 21 patients still on treatment with TKI. For 7 patients, the dose of TKI treatment had to be reduced due to co-morbidities (n = 2) or skin toxicity (rash ≥ grade 3; n = 5). These patients demonstrated a similar response and outcome as compared to patients receiving full dose TKI treatment. CONCLUSION: Patients with EGFR mutated NSCLC and the need for TKI dose reduction seem to benefit in a similar manner from TKI therapy.

Open, randomized, multi-center phase II study comparing efficacy and tolerability of Erlotinib vs. Carboplatin/Vinorelbin in elderly patients (>70 years of age) with untreated non-small cell lung cancer.

BACKGROUND: Targeting the epidermal-growth-factor-receptor (EGFR) in non-small cell lung cancer (NSCLC) is an established treatment option with less toxicity compared to conventional chemotherapy. This study was undertaken to determine whether Erlotinib is non-inferior compared to chemotherapy as a first-line therapy in unselected elderly patients. MATERIALS AND METHODS: Patients ≥ 70 years with untreated, metastatic NSCLC were randomized to Erlotinib (E), 150 mg/day or Carboplatin (AUC5) plus Vinorelbine (25mg/m(2) on days 1 and 8) every three weeks (CV). Primary endpoint was progression-free survival (PFS). After progression, crossover was strongly recommended. Secondary endpoints were duration of response, 1-year survival, overall survival (OS), response rate (RR), quality of life (FACT-L), assessment of comorbidities by simplified comorbidity score (SCS) and Charlsons' comorbidity score, safety and assessment of molecular markers. RESULTS: Between June 2006 and August 2008 284 pts were randomized to E (144) and CV (140). PFS was significantly inferior with E (median PFS 2.4 versus 4.6 months [HR 1.6, 75% CI 1.22-2.09, p: 0.0005]) as well as RR (7.8% v 28.3%, p: 0.0001). No significant difference in OS appeared (median E: 7.3 months versus CV: 8.4 months, HR: 1.24 [75% CI 0.9-1.71]). In never smokers PFS (median PFS: 3.7 v 4.3 m, E v CV, HR 0.72, 75% CI 0.35-1.48) and OS (median: 16.5 versus 17 months, HR 0.99 [75% CI 0.38-2.57]) were comparable. More skin toxicity and diarrhea was seen with E compared to more myelotoxicity, neurotoxicity and constipation with CV. Less severe adverse events were observed with E (81 v 102, E v CV). CONCLUSION: CV had an increased efficacy compared with E in an unselected population of elderly patients with advanced NSCLC.

[Treatment of non-small cell lung cancer]. / Behandlung des nichtkleinzelligen Lungenkarzinoms.

Within recent years, the treatment of non-small cell lung cancer has become increasingly heterogeneous and complex. New cytotoxic agents and drugs against molecular targets have been developed. Moreover, new indications for therapy such as maintenance therapy have been explored. In addition, by assessing defined molecular markers, it is possible to identify patients who may likely respond to a given treatment. This approach will continue in the future; thus, it will be possible to characterize patient into subgroups based on molecular, histological, or clinical markers. This review will summarize the current state of the art in the treatment of non-small cell lung cancer.

Palliative care concepts in respiratory disease.

Many respiratory diseases besides lung cancer are still not curable. There is an unmet need for palliative care, especially in non-malignant conditions. In this article we focus on symptomatic treatment of typical symptoms in respiratory disease beyond causal treatment.

[Palliative care in respiratory medicine]. / Palliativmedizin in der Pneumologie.

Palliative care should be part of respiratory medicine for two reasons: first, many respiratory diseases--besides thoracic tumours--need palliative care in the late stages of the disease. Second, dyspnoea is a common symptom in advanced, primary extrapulmonary diseases and the knowledge of respiratory specialists can be beneficial in the treatment of this symptom. In this paper we describe frequent symptoms of advanced pulmonary diseases and their treatment. Moreover, we focus on the structure of palliative care in Germany.

[Chemotherapy of malignant pleural mesothelioma: have we made any progress?]. / Systemtherapie des malignen Pleuramesothelioms: Gibt es Fortschritte?

Chemotherapy of malignant mesothelioma is of great importance because most patients with malignant pleural mesothelioma are diagnosed for the first time with widespread or advanced disease. Due to the small number of patients in clinical trials and due to difficulties in tumour assessment in the last 20 years, validation criteria for efficacy could only be defined with major limitations. After the introduction of modern antifolates in the chemotherapy for malignant mesothelioma and after the establishment of standardised response criteria, a significant prolongation of survival time by combination chemotherapy was shown in two randomised phase III trials. The combination of pemetrexed and cisplatin is the current standard of chemotherapy in malignant mesothelioma. Besides first-line therapy, there are also data to support the efficacy of chemotherapy in pretreated patients. In spite of the various results of preclinical trials which support the prognostic significance of certain targeted structures of intra- and intercellular signal transduction, no relevant efficacy could be shown for targeted therapies in mesothelioma up to now.