Abstract
Recent clinical trials evaluating the combination of chemotherapy with immune checkpoint inhibition for the primary treatment of lung cancer showed increased progression-free and overall survival compared with chemotherapy alone. However, the combination of these two modalities is less than additive and the mechanisms of resistance to this therapeutic intervention are discussed here. So far, the conventional biomarkers for immunotherapy, namely programmed death-ligand 1 expression or tumor mutational burden are poor predictors of the efficacy of immunochemotherapy, and the optimal sequence of chemotherapy and immunotherapy has yet to be defined.
Highlights
Lung cancer shows the highest incidence of tumor-related mortality and accounts for approximately 2 million new cases per year worldwide[1]
Immunotherapy is applied frequently for lung cancer patients in a primary or secondary setting, but again, marked benefits are limited to approximately 15% of patients, mostly characterized by high immune checkpoint www.cdrjournal.com
Regarding immune checkpoint-directed antibodies, similar results were obtained for chemotherapy combinations employing atezolizumab or nivolumab and are to be expected for other antibodies with the same specificity
Summary
Lung cancer shows the highest incidence of tumor-related mortality and accounts for approximately 2 million new cases per year worldwide[1]. Regarding immune checkpoint-directed antibodies, similar results were obtained for chemotherapy combinations employing atezolizumab or nivolumab and are to be expected for other antibodies with the same specificity The approval of this type of chemotherapy - immunotherapy combination is based on the phase III KEYNOTE-189 trial which randomized 616 patients with advanced, PD-L1-unselected, non-squamous NSCLC in a 2:1 ratio to chemotherapy (cisplatin/carboplatin with pemetrexed) with or without pembrolizumab[3,15,16]. The rate of severe AEs (≥ grade 3) was not significantly different for the pembrolizumab-combination and placebo groups (67% vs 66%) These results corroborated findings of the earlier phase II KEYNOTE-021 trial, which had randomized 123 stage III B or IV non-squamous NSCLC patients in a 1:1 ratio to chemotherapy with or without pembrolizumab and reported improved ORR (55% vs 29%) and median PFS (13.0 vs 8.9 months)[16].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
