Immunotherapy Alone or in Combination with Chemotherapy as First-Line Treatment of Non-Small Cell Lung Cancer
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Lung Cancer (HA Wakelee and TA Leal, Section Editors)
Immunotherapy Alone or in Combination with Chemotherapy as First-Line Treatment of Non-Small Cell Lung Cancer Puneet Saxena, MD1 Pawan Kumar Singh, MD, DM2 Prabhat Singh Malik, MD, DM3 Navneet Singh, MD, DM1,* Address *,1 Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India Email: [email protected] 2 Department of Pulmonary and Critical Care Medicine, Post Graduate Institute of Medical Sciences (PGIMS), University of Health Sciences, Rohtak, Haryana, India 3 Department of Medical Oncology, Dr. B.R.A.I.R.C.H, All India Institute of Medical Sciences, New Delhi, India
* Springer Science+Business Media, LLC, part of Springer Nature 2020
Puneet Saxena and Pawan Kumar Singh contributed equally to this work. Puneet Saxena and Pawan Kumar Singh are the joint first authors. This article is part of the Topical Collection on Lung Cancer Keywords Immune checkpoint inhibitors I Non small cell lung cancer I First line I Treatment I Immunotherapy I Metastatic I PD-L1 I PD-1 I Pembrolizumab I Atezolizumab
Opinion statement Immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic and selected cases of unresectable advanced non-small cell lung cancer (NSCLC). Importantly for patients, this implies that in the absence of a targetable oncogenic driver [especially epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements] and in the presence of high programmed death-ligand 1 (PD-L1) expression (≥ 50%), they are eligible for mono-therapy with pembrolizumab thereby avoiding chemotherapy as the first line of treatment. This mono-immunotherapy approach for high PD-L1 metastatic NSCLC is associated with improved overall survival (OS) and radiological responses (RR) with lesser toxicity as
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compared with conventional platinum doublet chemotherapy for both non-squamous and squamous histological types. However, majority of NSCLC patients either have no or low expression of PD-L1 (G 50%) and such patients derive greater benefit from a combination of PD-1/PD-L1 ICIs with platinum doublet chemotherapy as compared with chemotherapy alone. Again, benefits are seen for both OS and RRs. However, combining immunotherapy with chemotherapy, in general, does lead to higher toxicity than those seen with either of the two alone. Additionally, for non-squamous NSCLC patients, clinicians should not initiate ICI treatment till the results of common targetable genetic alterations like EGFR mutation, ALK, and ROS1 gene rearrangement testing are known (preferably on broad next generation sequencing) and are negative (even if results of PD-L1 testing are available)—as targeted therapies remain the cornerstone of treatment for patients harboring these oncogenic drivers. It is worth mentioning that PD-1 and PD-L1 ICIs are very expensive, and their usage is associated with occur
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