Radiotherapy plus immune checkpoint blockade in PD(L)-1-resistant metastatic NSCLC

Jonathan D Schoenfeld and colleagues1 report the findings of a randomised phase 2 clinical trial, in which two radiotherapy regimens known to modulate immune response in preclinical models were tested in patients with metastatic non-small-cell lung cancer (NSCLC) that was resistant to previous PD-(L...

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Bibliographic Details
Published in:The lancet oncology 2022-04, Vol.23 (4), p.e157-e157
Main Authors: Ochoa-de-Olza, Maria, Bourhis, Jean, Coukos, George, Herrera, Fernanda G
Format: Article
Language:English
Subjects:
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - radiotherapy
Clinical trials
Humans
Immune checkpoint
Immune Checkpoint Inhibitors
Immune response
Immunology
Inflammation
Lung Neoplasms - drug therapy
Lung Neoplasms - radiotherapy
Lymphocytes T
Metastases
Metastasis
Non-small cell lung carcinoma
Patients
PD-1 protein
Radiation Oncology
Radiation therapy
Small cell lung carcinoma
Tumors
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Summary:Jonathan D Schoenfeld and colleagues1 report the findings of a randomised phase 2 clinical trial, in which two radiotherapy regimens known to modulate immune response in preclinical models were tested in patients with metastatic non-small-cell lung cancer (NSCLC) that was resistant to previous PD-(L)1 inhibitor therapy. Unfortunately, the occurrence of abscopal effects might have been overestimated in patients, and randomised clinical trials have now convincingly proved that they are inherently incidental. [...]alternative approaches should be sought to leverage the immune effects of radiotherapy for combination treatments. [...]T-cell reinvigoration by anti-PD1 should be carefully timed to coincide with the peak of tumour antigen release following radiotherapy.5 Because therapy sequencing and schedule seem to be particularly important, it is possible that the widely spaced delivery of radiotherapy used by Schoenfeld and colleagues was insufficient to maintain the proinflammatory effects of radiotherapy.
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(22)00154-1