Radiotherapy and Immunotherapy Combinations for Lung Cancer
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LUNG CANCER (H BORGHAEI, SECTION EDITOR)
Radiotherapy and Immunotherapy Combinations for Lung Cancer Vishesh Agrawal 1 & Kimberly Thomas Benjamin 2 & Eric C. Ko 1,3 Accepted: 5 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Positive results from recent immunotherapy trials of non-small cell lung cancer (NSCLC) have coincided with a greater appreciation for the impact of radiation therapy (RT) on tumor immunity. Here, we summarize key clinical findings and ongoing efforts to combine immunotherapy and RT for the treatment of NSCLC. Recent Findings The role of immunotherapy for NSCLC has expanded significantly following the pivotal approvals of nivolumab and pembrolizumab for metastatic NSCLC, maintenance durvalumab in unresectable stage III NSCLC, and atezolizumab for metastatic NSCLC. Several small early-phase trials have demonstrated the ability of RT to elicit clinically significant tumor immunity. These positive findings support current trial efforts combining RT with immunotherapy for NSCLC. Summary Recently initiated trials of RT and immunotherapy hold significant promise in expanding the therapeutic options for NSCLC. Optimization of therapy will require careful patient selection to yield meaningful improvements in clinical outcomes. Keywords Radiation therapy . Immunotherapy . Immune checkpoint blockade . Checkpoint inhibitors . Abscopal effect . Stereotactic body radiation therapy
Abbreviations BED Biologically effective dose CPR Complete pathologic response CTLA-4 Cytotoxic T lymphocyte antigen-4 MPR Major pathologic response NSCLC Non-small cell lung carcinoma ORR Overall response rate OS Overall survival PD-1 Programmed cell death protein 1 PD-L1 Programmed cell death ligand 1 PFS Progression-free survival RT Radiation therapy SABR Stereotactic ablative body radiotherapy SBRT Stereotactic body radiation therapy This article is part of the Topical Collection on Lung Cancer * Eric C. Ko [email protected] 1
Department of Radiation Oncology, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
2
Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
3
Department of Radiation Oncology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
TMB TPS
Tumor mutational burden Tumor proportion score
Introduction Lung cancer is the second most common malignancy in the USA and is the leading cause of cancer-related deaths in both men and women [1]. It is often diagnosed at an advanced or metastatic stage, when treatment options tend to be of limited efficacy. Even when diagnosed and treated early, the clinical course of lung cancer is often characterized by recurrence with distant metastases. Major advances in locally advanced and metastatic lung cancer have been limited until trials of immunotherapy demonstrated responses to checkpoint inhibition in previously treated patients [2–4]. These studies led to multiple FDA-approved therapies
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