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March 1, 2019Clinical Cancer Research722 citationsOpen Access

Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes

DDDeborah B. DoroshowMSMiguel F. SanmamedKHKatherine Hastings

Key Points

  • To review clinical advances in immune-checkpoint inhibitors for non-small cell lung cancer and evaluate the predictive utility of emerging biomarkers.
  • Synthesized clinical trial outcomes evaluating PD-1 pathway inhibitors as monotherapy and in combination with chemotherapy across lines of treatment in advanced NSCLC.
  • Assessed predictive biomarkers, including PD-L1 expression levels, tumor mutational burden, and novel markers of tumor inflammation.
  • Immune-checkpoint inhibitor monotherapy improved overall survival compared with chemotherapy in the first-line setting for patients with PD-L1 expression on at least 50% of tumor cells, as well as in second-line or later therapy.
  • Combining immune-checkpoint inhibitors with chemotherapy prolonged overall survival in both squamous and nonsquamous NSCLC regardless of baseline PD-L1 expression.
  • PD-L1 expression and tumor mutational burden have not served as straightforward predictive biomarkers, driving ongoing investigation into novel tumor inflammation markers.

Abstract

Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non-small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.

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Cite This Study

Doroshow et al. (2019) studied this question.

synapsesocial.com/papers/69fe9b3e6018b8d0892d5803https://doi.org/10.1158/1078-0432.ccr-18-1538
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