Preface
Michaël Duruisseaux, MD, PhD Respiratory Department, Hôpital Louis Pradel Hospices Civiles de Lyon Cancer Institute Lyon, France
Dear Colleagues,
The struggle against the devastating consequences of lung cancer is ongoing at many levels and appears to have reached important milestones, including effective combinations of novel drug classes and the targeting of an increasing number of driver aberrations. Immunotherapy was again a major aspect at this year’s annual congress of the European Society for Medical Oncology (ESMO) that took place at Barcelona, Spain, from 27th September to 1st October. Meanwhile, the activity of immune checkpoint inhibitors has been well documented, although of course only a certain percentage of patients will benefit from treatment. Biomarker research has thus become a major focus in the further development of these drugs. Besides PD-L1 expression, other parameters such as tumor mutational burden are being explored, with mixed results.
Immunotherapy improves outcomes when administered together with other therapies such as cytotoxic agents, but also appears to combine well with antiangiogenic drugs based on synergy at the tumor microenvironment level. These insights might fuel new therapeutic algorithms, particularly in patients without driver mutations. On the other hand, in the setting of EGFR-mutant lung cancer, angiogenesis-targeted drugs are also potential combination partners for EGFR tyrosine kinase inhibitors. Studies conducted with combined frontline regimens have revealed convincing findings in this area. More importantly, new evidence has also been generated on the topic of the ideal treatment sequence in patients with EGFR-positive disease. The use of third-generation EGFR TKI emerges as the preferred therapeutic strategy in the first-line setting for EGFR-positive patients.
Another important field of research is the identification and targeting of rare fusions such as those of the ALK, ROS1, NTRK, RET and NRG1 genes. Despite low prevalence rates, this is worth the effort as it can enable very successful treatment in a setting where other options might not elicit meaningful responses. Novel and known agents are being assessed for their activity in rare aberrations.
Finally, essential steps have been taken by eventually improving survival in patients with small-cell histology. Immunotherapy has established new horizons in small-cell tumors, with recent analyses showing that these benefits are independent of the biomarker status.
In their entirety, these new insights will hopefully contribute to improving treatment and adding precious time and quality of life to our patients’ lives.
More posts
Even infrequent actionable drivers are important
NRG1 fusions are oncogenic events, i.e., transforming events that occur in all tumor types, although in fairly low frequencies. Their prevalence is less than 1 % throughout all tumor types. Some reports have estimated the NRG1 fusion prevalence at approximately 0.2 %. Although NRG1 fusions are not a common event, they represent an important actionable driver.
CNS disease does not preclude successful treatment
Brain metastases occur in approximately 35 % of patients with metastatic NSCLC and are associated with a variety of neurological symptoms, as well as poor prognosis. However, little is known about the prognostic impact of the symptomatic burden of CNS lesions at the time of diagnosis. This was assessed by an analysis based on a real-life cohort of 1,608 NSCLC patients from the Vienna Brain Metastasis Registry with newly diagnosed brain metastases.
Innovations in the setting of rare mutations: ALK, ROS1, NTRK, NRG1
Oncogene-directed treatment requires molecular testing, but, as is known, limitations related to tissue collection and tissue-based testing can represent a serious obstacle in clinical practice. Blood-based next generation sequencing (NGS) has the potential to overcome some of these limitations.
Exploring synergy between anti-angiogenic drugs and immunotherapy
In the setting of non-squamous advanced NSCLC without actionable driver mutations, the advent of immune checkpoint inhibitor therapy has led to the implementation of new standards. Synergistic effects can be expected from anti-angiogenic treatment. The vascular endothelial growth factor (VEGF) has been shown to create an immunosuppressive tumor microenvironment by modifying immune cell function besides promoting angiogenesis.
Frontline combinations of EGFR- and angiogenesis-targeted agents
In patients with untreated EGFR-mutant tumors, it has been shown that the addition of the anti-VEGF antibody bevacizumab to first-generation EGFR TKIs induces PFS benefits with an acceptable toxicity profile. The open-label, randomized, multicenter, phase III ARTEMIS (CTONG 1509) study is the first phase III trial to test bevacizumab plus erlotinib in Chinese NSCLC patients.
EGFR-positive tumors: the issue of optimal therapy across several lines
In patients with advanced, EGFR-positive NSCLC, EGFR tyrosine kinase inhibitors (TKIs) represent the frontline treatment standard. Three generations of TKIs are widely available, but the ideal sequence is currently unknown. The phase III, double-blind, randomized FLAURA trial compared the third-generation EGFR TKI osimertinib with the first-generation agents gefitinib and erlotinib in the frontline setting.