Publications by authors named "David Heigener"

Palliative medicine is an essential part in the treatment of patients with advanced or metastatic NSCLC. A structured palliative approach beginning from diagnoses improves quality of life and maybe even prolong survival. Besides symptom control, the disease trajectory and prognosis should regularly be re-evaluated and discussed with the patient and his loved ones.

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Alternative sources of tumour information need to be explored in patients with non-small cell lung cancer (NSCLC). Here, we compared programmed cell death ligand 1 (PD-L1) expression on cytology imprints and circulating tumour cells (CTCs) with PD-L1 tumour proportion score (TPS) from immunohistochemistry staining of tumour tissue from patients with NSCLC. We evaluated PD-L1 expression using a PD-L1 antibody (28-8) in representative cytology imprints, and tissue samples from the same tumour.

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Immune checkpoint inhibition of programmed-death receptor 1 (PD-1) or its ligand (PD-L1) has become a standard in the treatment of metastatic non-small cell lung cancer, either as monotherapy or in combination. Recently, it could be shown that immunotherapy works as consolidation after chemoradiotherapy in locally advanced disease if the tumours express PD-L1. A significant and meaningful survival benefit for consolidation with durvalumab after chemoradiotherapy compared to chemoradiotherapy alone was observed in the PACIFIC trial.

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Despite the highly immunogenic potential of small cell lung cancer (SCLC), progress in evaluating the therapeutic value of immune checkpoint agents has lagged behind that of non-small cell lung cancer. Results from a number of phase I-III clinical trials that specifically address the use of anti-PD-1, anti-PD-L1 and anti-CTLA-4 agents in SCLC have now been reported. This review will focus on the available evidence for immune checkpoint blockade in SCLC and review current biomarker strategies with the aim of providing perspective and interpretation of this data for clinical practice.

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Metastatic non-small-cell lung cancer is still a devastating disease; however, treatment options have diversified dramatically in the past two decades. From unselected platinum-based chemotherapy for all patients, several different treatment groups have evolved, that is, those with "druggable" targets, those with a promising immune signature, and those without any predicting factors outlined in this article. Challenge includes the intersections between these groups and the optimal treatment path.

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Crizotinib.

Recent Results Cancer Res

November 2018

Crizotinib is an ATP-competitive small-molecule inhibitor of the receptor tyrosine kinases (RTK) C-Met, ALK and ROS1. There is a robust effectiveness in non-small-cell lung cancer (NSCLC) harbouring EML4-ALK-rearrangements resulting in constitutional activation of the ALK-RTK. The drug is approved for this entity, which represents no more than 3-5% of all NSCLC.

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PD-L1 and PD-1 inhibitors were both developed to combat a huge array of cancers. Both classes of agents block the PD-1/PD-L1 pathway. Unlike PD-1 inhibitors, PD-L1 inhibitors do also block the B-7.

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Background: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months.

Objective: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT.

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 Elderly patients (70 years or older) with non-small cell lung cancer (NSCLC) do benefit from systemic chemotherapy as shown in many studies. We prospectively collected multicentric data on therapeutic decisions from patients 70 years or older to reflect the reality in the German health care system.  Patients 70 years or older with NSCLC Stage IIIB or IV were eligible.

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Background: Guidelines provide treatment recommendations for advanced non-small-cell lung cancer (NSCLC), but physicians must also consider other factors. We surveyed physicians treating NSCLC to determine their therapy goals, drivers of treatment choice, current prescribing behavior, and therapy expectations.

Materials And Methods: In 2015, an online survey was conducted of 500 pulmonologists/oncologists treating lung adenocarcinoma in Germany, France, Italy, Spain, and the United Kingdom, comprising screening and therapy decision questions.

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Quality of life (QoL) is important to cancer patients and is increasingly included as a trial end point. The methodologies/findings of randomized controlled trials evaluating the efficacy and safety of second-line treatments approved for use in the EU in patients with advanced/metastatic NSCLC, without known targetable mutations, were evaluated. Seven trials were identified; five compared active treatments and two compared active treatment to placebo.

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Treatment for small-cell lung cancer (SCLC) has changed little over the past few decades; available therapies have failed to extend survival in advanced disease. In recent years, immunotherapy with treatments such as interferons, TNFs, vaccines and immune checkpoint inhibitors has advanced and shown promise in the treatment of several tumor types. Immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab, durvalumab, tremelimumab and ulocuplumab are at the forefront of immunotherapy and have achieved approvals for certain cancer types, including melanoma (ipilimumab, nivolumab and pembrolizumab), non-SCLC (nivolumab and pembrolizumab) and renal cell carcinoma (nivolumab).

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Background: Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naïve (TKI-naïve) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown.

Materials And Methods: In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled.

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The MAP-kinase pathway, consisting of the kinases RAS, RAF, MEK, and ERK, is crucial for cell proliferation, inhibition of apoptosis, and migration of cells. Direct inhibition of RAS is not yet possible, whereas inhibition of RAF is already established in malignant melanoma and under investigation in non-small-cell lung cancer (NSCLC). Due to their structure and function, the MEK proteins are attractive targets for cancer therapy and are also under investigation in NSCLC.

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Immune evasion is recognized as a key strategy for survival and progression of several cancer entities including non-small cell lung cancer. Hence, various approaches to restore anti-tumor immune responses are currently investigated. In particular, agents targeting immune checkpoint receptors, such as the cytotoxic T-lymphocyte antigen-4 receptor and programmed death-1 receptor have shown promise in early clinical trials.

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Purpose Of Review: The fact that growth and spread of tumours are dependent on angiogenesis has led to the investigation of the role of antiangiogenic agents in the therapeutic strategies for thoracic tumours such as nonsmall cell lung cancer (NSCLC). This review summarizes and evaluates the recent developments in this field.

Recent Findings: Bevacizumab, an antivascular endothelial growth factor antibody, has been approved for the treatment of patients with advanced NSCLC of nonsquamous histology in combination with a platinum-containing chemotherapy.

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Immune evasion is recognized as a key strategy for cancer survival and progression. With increased understanding of immune escape mechanisms, the development of immunotherapies to restore anti-tumor immune responses has flourished. Immuno-oncology (I-O) agents targeting checkpoints in the immune regulation cascade currently form the mainstay of approaches of cancer immunotherapy.

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The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance.

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An unmet need remains for effective, well-tolerated treatment options in advanced non-small-cell lung cancer that can alleviate the disease burden for a broad selection of patients. Nintedanib (Vargatef) is a potent, oral, triple angiokinase inhibitor of three distinct pro-angiogenic pathways. A recent Phase III trial of second-line nintedanib plus docetaxel met the primary end point of progression-free survival and demonstrated significant benefit in the key secondary end point of overall survival, with median overall survival greater than 1 year for patients with adenocarcinoma histology.

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Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately differentiated neoplasms. They comprise a large variety of rare and heterogeneous tumors with an estimated incidence of 3-5/100,000/year.

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Crizotinib.

Recent Results Cancer Res

September 2014

Crizotinib is an ATP-competitive small-molecule inhibitor of the receptor tyrosine kinases (RTK) c-Met, anaplastic lymphoma kinase (ALK), and ROS1. There is convincing clinical evidence for the effectiveness in non-small-cell lung cancer (NSCLC) harboring EML4-ALK rearrangements resulting in constitutional activation of the ALK-RTK. The drug is approved for this entity, which represents no more than 3-5% of all NSCLC.

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