Michaël Duruisseaux, MD, PhD Respiratory Department, Hôpital Louis Pradel Hospices Civiles de Lyon Cancer Institute Lyon, France
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.