Abstract
Immune checkpoint inhibitors (ICIs) have significantly improved overall survival (OS) in metastatic non-small cell lung cancer (m-NSCLC). However, not all patients with m-NSCLC benefit from ICIs, and resistance to ICIs is an emerging challenge. The tumour microenvironment (TME) is immunosuppressive, and provides a myriad of mechanisms to facilitate escape of cancer cells from immune surveillance. The TME may also dampen the response to ICIs by inhibiting T cell effector responses. The poor prognosis of m-NSCLC has led to investigation of ICIs combined with other treatments with the intention of modulating the TME and sensitizing tumours to the effects of ICIs. Stereotactic ablative radiotherapy (SABR) in combination with ICIs is an area of intense interest. SABR is thought to evoke a pro-immunogenic response in the TME, with the capacity to turn a “cold”, unresponsive tumour to “hot” and receptive to ICI. In addition to improved local response, SABR is postulated to produce a heightened systemic immune response when compared to conventional radiotherapy (RT). Preclinical studies have demonstrated a synergistic effect of SABR + ICIs, and clinical studies in m-NSCLC showed safety and promising efficacy compared to systemic therapies alone. To optimize ICI + SABR, ICI choice, combinations, dosing and length of treatment, as well as sequencing of ICI + SABR all require further investigation. Appropriate sequencing may depend on the ICI(s) being utilized, with differing sites of metastases possibly eliciting differing immune responses. Single versus multisite radiation is controversial, whilst effects of irradiated tumour volume and nodal irradiation are increasingly recognized. Taken together, there is strong preclinical and biological rationale, with emerging clinical evidence, supporting the strategy of combining SABR + ICIs in m-NSCLC.
| Original language | English |
|---|---|
| Pages (from-to) | 2766-2778 |
| Number of pages | 13 |
| Journal | Translational Lung Cancer Research |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 01 Jun 2021 |
| Externally published | Yes |
Bibliographical note
Funding Information:ICMJE uniform disclosure form (available at http:// dx.doi.org/10.21037/tlcr-20-1117). The series “Lung cancer and the immune system” was commissioned by the editorial office without any funding or sponsorship. PJN reports grants from BMS, Roche Genentech, Allergan, and Compugen, outside the submitted work. TJ reports personal fees from Astra Zeneca, BMS, Novartis, MSD, Merck-Sorrono, Boehringer-Ingelheim, Roche, and Pfizer, outside the submitted work. GGH reports personal fees from Astra Zeneca, outside the submitted work. SS reports grants from Varian Industries, Merck-Sharp-Dohme, Astra Zeneca, and Bayer Pharmaceuticals, outside the submitted work. SS reports personal fees from Bristol Meyer Squibb, Astellas, Reflexion, Astra Zeneca, Roche, and Varian, outside the submitted work. The authors have no other conflicts of interest to declare.
Publisher Copyright:
© 2021 AME Publishing Company. All rights reserved.
Keywords
- Immune checkpoint inhibitors (ICIs)
- Non-small cell lung cancer (NSCLC)
- Radiotherapy
- Stereotactic body radiation therapy (SBRT)
- Lung Cancer
- Immunotherapy
ASJC Scopus subject areas
- Oncology
Access to Document
- A narrative review of combined stereotactic ablative radiotherapy and immunotherapy in metastatic non-small cell lung cancer
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