Stereotactic Ablative Radiotherapy With or Without Immunotherapy for Early-Stage or Isolated Lung Parenchymal Recurrent Node-Negative Non-Small-Cell Lung Cancer: An Open-Label, Randomised, Phase 2 Trial

Authors

Joe Y Chang
Steven H Lin
Wenli Dong
Zhongxing Liao
Saumil J Gandhi
Carl M Gay
Jianjun Zhang
Stephen G Chun
Yasir Y Elamin
Frank V Fossella
George Blumenschein
Tina Cascone
Xiuning Le
Jenny V Pozadzides
Anne Tsao
Vivek Verma
James W Welsh
Aileen B Chen
Mehmet Altan
Reza J Mehran
Ara A Vaporciyan
Stephen G Swisher
Peter A Balter
Junya Fujimoto
Ignacio I Wistuba
Lei Feng
J Jack Lee
John V Heymach

Publication Date

9-9-2023

Journal

Lancet

Abstract

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC.

METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older with histologically proven treatment-naive stage IA-IB (tumour size ≤4 cm, N0M0), stage IIA (tumour size ≤5 cm, N0M0), or stage IIB (tumour size >5 cm and ≤7 cm, N0M0) as per the American Joint Committee on Cancer version 8 staging system or isolated parenchymal recurrences (tumour size ≤7 cm) NSCLC (T

FINDINGS: From June 30, 2017, to March 22, 2022, 156 participants were randomly assigned, and 141 participants received assigned therapy. At a median 33 months' follow-up, I-SABR significantly improved 4-year event-free survival from 53% (95% CI 42-67%) with SABR to 77% (66-91%; per-protocol population, hazard ratio [HR] 0·38; 95% CI 0·19-0·75; p=0·0056; ITT population, HR 0·42; 95% CI 0·22-0·80; p=0·0080). There were no grade 3 or higher adverse events associated with SABR. In the I-SABR group, ten participants (15%) had grade 3 immunologial adverse events related to nivolumab; none had grade 3 pneumonitis or grade 4 or higher toxicity.

INTERPRETATION: Compared with SABR alone, I-SABR significantly improved event-free survival at 4 years in people with early-stage treatment-naive or lung parenchymal recurrent node-negative NSCLC, with tolerable toxicity. I-SABR could be a treatment option in these participants, but further confirmation from a number of currently accruing phase 3 trials is required.

FUNDING: Bristol-Myers Squibb and MD Anderson Cancer Center Alliance, National Cancer Institute at the National Institutes of Health through Cancer Center Core Support Grant and Clinical and Translational Science Award to The University of Texas MD Anderson Cancer Center.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Chronic Disease, Immunotherapy, Lung Neoplasms, Neoplasm Staging, Nivolumab, Recurrence, Small Cell Lung Carcinoma, Treatment Outcome, Adolescent, Adult, Non-small cell lung cancer, stereotactic ablative radiotherapy, stereotactic body radiotherapy, immunotherapy, recurrence

DOI

10.1016/S0140-6736(23)01384-3

PMID

37478883

PMCID

PMC10529504

PubMedCentral® Posted Date

9-9-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes