David R. Gandara, MD Professor of Medicine UC Davis Comprehensive Cancer Center Sacramento, California, USA
Remarkable data in the field of lung cancer with potentially practice-changing impact have been presented at this year’s ESMO Congress that took place in Madrid, Spain, from 8th to 12th September, 2017. Immunotherapeutic approaches again constituted a major topic, as clinical researchers are tirelessly exploring the multitude of conditions and limitations determining the optimal use of these drugs.
This issue of memo inOncology delineates analyses of the OAK and POPLAR trials that confirmed the activity of the PD-L1 inhibitor atezolizumab regardless of PD-L1 expression and showed that assessment of tumour mutational burden in patient blood is feasible and correlates with treatment benefits. The PD-L1 inhibitor durvalumab excelled in the PACIFIC trial in patients with stage III lung cancer, thus providing an answer to a significant unmet need. Further analyses related to the activity of the PD-1 inhibitor nivolumab in the elderly and the optimal treatment duration with nivolumab.
Likewise, immunostimulation with the toll-like receptor 9 agonist lefitolimod is a promising approach in patients with extensive-disease small-cell lung cancer. Another indication suitable for the use of immunotherapeutic agents appears to be mesothelioma, which is known to confer poor prognosis. Several analyses presented at the ESMO 2017 Congress suggested clinically meaningful benefits of various immunotherapeutic agents in patients with malignant pleural mesothelioma.
In the area of targeted therapies, the debate on sequencing of drugs is gaining momentum, as head-to-head comparisons have shown superiority of potent later-generation drugs over established first-line compounds. This is true for the EGFR tyrosine kinase inhibitor osimertinib, which outperformed gefitinib and erlotinib in EGFR-mutant lung cancer, as well as for the ALK inhibitor alectinib that gave rise to improvements in progression-free survival and central nervous system outcomes when compared to crizotinib in the ALK-positive setting. The optimal succession of agents across several treatment lines, which is crucial for the achievement of the maximum survival benefit, still needs to be determined.
Last but not least, progress has been made with regard to targeted approaches that are under investigation for patients with rare driver mutations such as BRAF. When administered in a combined fashion, the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib showed substantial anti-tumour activity as a first-line strategy in BRAF-positive lung cancer patients.