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
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 chemoradioth...
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| Published in | The Lancet (British edition) Vol. 402; no. 10405; pp. 871 - 881 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
09.09.2023
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Summary: | 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.
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 (TanyNanyM0 before definitive surgery or chemoradiotherapy) were included in this trial. Participants were randomly assigned (1:1; using the Pocock & Simon method) to receive SABR with or without four cycles of nivolumab (480 mg, once every 4 weeks, with the first dose on the same day as, or within 36 h after, the first SABR fraction). This trial was unmasked. The primary endpoint was 4-year event-free survival (local, regional, or distant recurrence; second primary lung cancer; or death). Analyses were both intention to treat (ITT) and per protocol. This trial is registered with ClinicalTrials.gov (NCT03110978) and is closed to enrolment.
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.
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.
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. |
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| Bibliography: | SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Undefined-1 content type line 23 ObjectType-Article-3 IIW: Investigation, methodology, project administration, resources and writing– review & editing SJG: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing PAB: Investigation, methodology, resources and writing– review & editing GB: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing VV: Formal analysis/interpretation, investigation, methodology, validation, visualisation, writing – original draft, and writing– review & editing WLD: Data/sample curation/collection, formal analysis/interpretation, investigation, methodology, project administration, resources, validation, visualisation, writing – original draft, and writing– review & editing AAV: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing CONTRIBUTORS JF: Investigation, methodology, project administration, resources and writing– review & editing FVF: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing JVP: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing SHL: Data/sample curation/collection, formal analysis/interpretation, investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing YYE: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing AT: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing RJM: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing MA: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing CMG: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing SGS: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing JVH: Conceptualisation/study design, formal analysis/interpretation, funding acquisition, investigation, methodology, project administration, resources, patient screen/enrollment, supervision, validation and writing– review & editing TC: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing JWW: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing ZXL: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing JYC: Conceptualisation/study design, data/sample curation/collection, formal analysis/interpretation, funding acquisition, investigation, methodology, project administration, resources, patient screen/enrollment, supervision, validation, visualisation, writing – original draft, and writing– review & editing SGC: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing JYC, WLD, LF, JJL and JVH had full access to all the data in the study and had final responsibility for the decision to submit for publication, and directly accessed and verified the underlying data reported in the manuscript. LF: Conceptualisation/study design, data/sample curation/collection, formal analysis/interpretation, investigation, methodology, project administration, resources, and writing– review & editing JJL: Conceptualisation/study design, data/sample curation/collection, formal analysis/interpretation, investigation, methodology, project administration, resources, and writing– review & editing JZ: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing ABC: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing XL: Investigation, methodology, project administration, resources, patient screen/enrollment and writing– review & editing |
| ISSN: | 0140-6736 1474-547X 1474-547X |
| DOI: | 10.1016/S0140-6736(23)01384-3 |