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.

The Combined Therapy of Cabozantinib, Crizotinib, and Osimertinib in a Lung Cancer Patient with Acquired MET Amplification and Resistance Mutations.

EGFR-mutant lung cancers develop a wide range of potential resistance alterations under therapy with the third-generation EGFR tyrosine kinase inhibitor osimertinib. MET amplification ranks among the most common acquired resistance alterations and is currently being investigated as a therapeutic target in several studies. Nevertheless, targeted therapy of MET might similarly result in acquired resistance by point mutations in MET, which further expands therapeutic and diagnostic challenges.

NSCLC with uncommon EGFR mutations treated with atezolizumab plus bevacizumab and chemotherapy.

Objectives: For refractory NSCLC patients with EGFR mutations, recent studies have demonstrated a favorable response to the combination of anti-angiogenic therapy and checkpoint inhibition but included only very few patients with uncommon EGFR mutations for which treatment options are still limited despite new targeted treatments.

Materials And Methods: Sixteen stage IV NSCLC patients with uncommon EGFR mutations from 9 different German centers were treated in first or further line with Atezolizumab, Bevacizumab, Carboplatin and (nab-)Paclitaxel (ABCP). PFS was evaluated from start of ABCP and OS from time of initial diagnosis of stage IV.

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers.

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.

Diagnostic, Clinical and Post-SARS-CoV-2 Scenarios in Cancer Patients with SARS-CoV-2: Retrospective Analysis in Three German Cancer Centers.

Oncologists face challenges in the management of SARS-CoV-2 infections and post-SARS-CoV-2 cancer treatment. We analyzed diagnostic, clinical and post-SARS-CoV-2 scenarios in patients from three German cancer centers with RT-PCR confirmed SARS-CoV-2 infection. Sixty-three patients with SARS-CoV-2 and hematologic or solid neoplasms were included.

Comparison of Resistance Spectra after First and Second Line Osimertinib Treatment Detected by Liquid Biopsy.

Since 2009, several first, second, and third generation tyrosine kinase inhibitors (TKI) have been approved for targeted treatment of mutated metastatic non-small lung cancer (NSCLC). A vast majority of patients is improving quickly on treatment; however, resistance is inevitable and typically occurs after one year for TKI of the first and second generation. Osimertinib, a third generation TKI, has recently been approved for first line treatment in the palliative setting and is expected to become approved for the adjuvant setting as well.

KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315).

Objectives: After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany.

Patients And Methods: A total of 1039 patients with advanced KRAS-mutant or -wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019 by 98 centers in Germany.

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP.

Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.

Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and safety from the German expanded-access program (EAP).

Background: Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.

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.

Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer.

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies.

Efficacy of the irreversible ErbB family blocker afatinib in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-pretreated non-small-cell lung cancer patients with brain metastases or leptomeningeal disease.

Introduction: Afatinib is an effective first-line treatment in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) and has shown activity in patients progressing on EGFR-tyrosine kinase inhibitors (TKIs). First-line afatinib is also effective in patients with central nervous system (CNS) metastasis. Here we report on outcomes of pretreated NSCLC patients with CNS metastasis who received afatinib within a compassionate use program.

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer.

Background: Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients.

Methods: Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups.

First-line systemic treatment with gefitinib in stage IV non-small cell lung cancer.

Lung cancer has a high mortality rate and is often diagnosed in locally advanced or metastatic stages. A new therapeutic option for patients with non-small cell lung cancer (NSCLC) in these stages with progress or relapse after platinum-based chemotherapy exists in the inhibitors of the epidermal growth factor receptor (EGFR) tyrosine-kinase. EGFR tyrosine-kinase inhibitor treatment might also be an option for patients ineligible for surgery and conventional chemotherapy.

Preoperative chemotherapy with and without additional radiochemotherapy: benefit and risk for surgery of stage III non-small cell lung cancer.

Objective: Multi-modality approaches are increasingly employed to improve prognosis in surgically treated stage III non-small cell lung cancer (NSCLC). Risk and benefit of the preoperative therapeutic chemotherapy or combined radiochemotherapy on surgical morbidity and mortality are still a matter of debate.

Methods: In 1995, a national phase III trial was started to compare (arm A) preoperative chemotherapy followed by twice-daily chemoradiation and consecutive surgery, with (arm B) preoperative chemotherapy alone followed by surgery and consecutive radiotherapy.

Signal transduction pathways as novel therapy targets in lung cancer.

Cytotoxic therapy for lung-cancer patients has only moderately improved during the last decades. Simultaneously, efforts of intensive research to increase our understanding of the molecular basis of lung cancer have been undertaken. The cancer cell has been characterised by several genetic changes that lead to altered cellular functions.

Non-small-cell lung cancer: multimodality approach in stage-III resectable disease.

The long-term results of surgery +/- radiotherapy in patients with operable disease of locally advanced non-small-cell lung cancer are discouraging. In the vast majority, disseminated microscopic disease, resulting in the later occurrence of distant metastases, contributes substantially to this poor long-term outcome. The further development of multimodality treatment approaches in randomised trials, including effective systemic therapy, is necessary.

Combined modality treatment for locally advanced non-small cell lung cancer: preoperative chemoradiation does not result in a poorer quality of life.

The German Lung Cancer Cooperative Group (GLCCG) is assessing the impact of chemoradiation in addition to chemotherapy in the neoadjuvant treatment of stage III NSCLC. After three cycles of cisplatin/etoposide patients receive either hyperfractionated radiotherapy (RT) with concurrent carboplatin/vindesine and then surgery (arm A) versus surgery and then conventional RT (arm B). Quality of life (QL) was assessed throughout therapy using the EORTC QLQ-C30 and EORTC QLQ-LC 13.