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Immunotherapy Alone or in Combination with Chemotherapy as First-Line Treatment of Non-Small Cell Lung Cancer

  • Lung Cancer (HA Wakelee and TA Leal, Section Editors)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

A Correction to this article was published on 12 September 2020

This article has been updated

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 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 (< 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 occurrence of immune-related adverse events (irAEs) which occasionally can be severe. Hence, it is important to discuss efficacy, toxicity, and cost-related to ICI treatment with each and every patient at diagnosis in order to help them decide if they are willing to go ahead with this form of therapy either singly (for high PD-L1 expressors) or in combination with chemotherapy (for others).

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Change history

  • 12 September 2020

    The original version of this article unfortunately contained mistakes. In Table 2, under the column 'Lead to death' in Row 5 [CheckMate-026], the figures should read as '0.7' for Experimental Arm and '1.1' for Comparator. Right now, these are printed as 0.007 and 0.011 respectively.

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  1. Puneet Saxena and Pawan Kumar Singh contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India

    Puneet Saxena MD & Navneet Singh MD, DM

  2. Department of Pulmonary and Critical Care Medicine, Post Graduate Institute of Medical Sciences (PGIMS), University of Health Sciences, Rohtak, Haryana, India

    Pawan Kumar Singh MD, DM

  3. Department of Medical Oncology, Dr. B.R.A.I.R.C.H, All India Institute of Medical Sciences, New Delhi, India

    Prabhat Singh Malik MD, DM

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Correspondence to Navneet Singh MD, DM.

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Saxena, P., Singh, P.K., Malik, P.S. et al. Immunotherapy Alone or in Combination with Chemotherapy as First-Line Treatment of Non-Small Cell Lung Cancer. Curr. Treat. Options in Oncol. 21, 69 (2020). https://doi.org/10.1007/s11864-020-00768-2

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