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Clinical Trial
. 2023 Sep 9;402(10405):871-881.
doi: 10.1016/S0140-6736(23)01384-3. Epub 2023 Jul 18.

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

Joe Y Chang  1 , Steven H Lin  2 , Wenli Dong  3 , Zhongxing Liao  2 , Saumil J Gandhi  2 , Carl M Gay  4 , Jianjun Zhang  4 , Stephen G Chun  2 , Yasir Y Elamin  4 , Frank V Fossella  4 , George Blumenschein  4 , Tina Cascone  4 , Xiuning Le  4 , Jenny V Pozadzides  4 , Anne Tsao  4 , Vivek Verma  2 , James W Welsh  2 , Aileen B Chen  2 , Mehmet Altan  4 , Reza J Mehran  5 , Ara A Vaporciyan  5 , Stephen G Swisher  5 , Peter A Balter  6 , Junya Fujimoto  7 , Ignacio I Wistuba  7 , Lei Feng  3 , J Jack Lee  3 , John V Heymach  4
Affiliations
Clinical Trial

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

Joe Y Chang et al. Lancet. .

Erratum in

  • Department of Error.
    [No authors listed] [No authors listed] Lancet. 2023 Sep 9;402(10405):850. doi: 10.1016/S0140-6736(23)01852-4. Lancet. 2023. PMID: 37689410 No abstract available.

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 (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.

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.

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Conflict of interest statement

Declaration of interests ABC reports grants from Blue Halo, Proteus Consortium/Pfizer, and Novocure. YYE reports consulting fees from Takeda, Bristol-Myers Squibb, AstraZeneca, Spectrum, and Sanofi. AT reports consulting fees from Ariad, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, Seattle Genetics, Gilead Sciences, and Summit Therapeutics. PAB reports grants from Raysearch and Varian; and is a member of the advisory board for Raysearch/Raycare. CMG reports grants from AstraZeneca; royalties from UpToDate; honoraria from AstraZeneca, BeiGene, MJH Healthcare, and Targeted Oncology; patents pending related to small cell lung cancer; and advisory board payments from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, G1 Therapeutics, Jazz Pharmaceuticals, and MonteRosa Therapeutics. TC reports funding from Bristol-Myers Squibb; grants from Bristol-Myers Squibb, MedImmune/AstraZeneca, and EMD Serono; consulting fees from MedImmune/AstraZeneca, Bristol-Myers Squibb, Regeneron, EMD Serono, Merck, Genentech, Arrowhead Pharmaceuticals, and Mark Foundation for Cancer Research; honoraria from Bristol-Myers Squibb and IDEOlogy Health; travel grants from IDEOlogy Health, Bristol-Myers Squibb, and Dava Oncology; and advisory fees from MedImmune/AstraZeneca, Bristol-Myers Squibb, Regeneron, EMD Serono, Merck, Genentech, and Arrowhead Pharmaceuticals. SGC reports grant funding from the National Institutes for Health (R50CA275822); consulting fees from AstraZeneca, CurioScience, and Norton Healthcare; honoraria from Binaytara Foundation; and travel grants from ViewRay and AstraZeneca. GB reports grant funding from Amgen, Bayer, Adaptimmune, Elelixis, Daiichi Sankyo, GlaxoSmithKline, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, Torque, AstraZeneca, Bristol-Myer Squib, Celgene, Genentech, MedImmune, Merck, Novartis, Roche, Sanofi, Xcovery, Tmunity Therapeutics, Regeneron, BeiGene, Repertoire Immune Medicines, Verastem. CytomX Therapeutics, Duality Biologics, Mythic Therapeutics, Takeda, and Aulos Bioscience; consulting fees from AbbVie, Adicet, Amgen, Ariad, Bayer, Clovis Oncology, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Instil Bio, Genentech, Genzyme, Gilead, Lilly, Janssen, MedImmune, Merck, Novartis, Roche, Sanofi, Tyme Oncology, Xcovery, Virogin Biotech, Maverick Therapeutics, BeiGene, Rgeneron, Cytomx Therapeutics, Intervenn Biosciences, Onconova Therapeutics, Seagen, and Scorpion Therapeutics; advisory fees from Maverick Therapeutics and Virogin Biotech; stock or stock options in Virogin Biotech; and has an immediate family member employed by Johnson & Johnson (Janssen). XL reports grants from Eli Lilly, EMD Serono, Boehringer Ingelheim, and Regeneron; and consulting fees from EMD Serono, AstraZeneca, Spectrum Pharmaceutics, Novartis, Eli Lilly, Boehringer Ingelheim, Hengrui Therapeutics AstraZeneca, Janssen, Blueprint Medicines, Sensei Biotherapeutics, Daiichi Sankyo, Regeneron, AbbVie, and AMVent. SJG reports grants from Bristol-Myers Squibb, Nanobiotix, and Bristol-Myers Squibb Foundation; and travel grants from AstraZeneca. JZ reports funding from the National Cancer Institute of the National Institutes for Health Research Project Grant (R01CA234629), the AACR-Johnson & Johnson Lung Cancer Innovation Science Grant (18-90-52-ZHAN), the MD Anderson Physician Scientist Programme, and the MD Anderson Lung Cancer Moon Shot Programme; consulting fees from Johnson and Johnson, AstraZeneca, and Novartis; honoraria from Novartis, Bristol Myers Squibb, AstraZeneca, GenePlus, Innovent, and Hengrui; advisory fees from Novartis, AstraZeneca, GenePlus, and Catalyst; and receipt of other services from Novartis, Johnson and Johnson, and Merck. JJL reports grant funding from the National Cancer Institute (P30CA016672). SHL reports grants from Nektar Therapeutics, Beyond Spring Pharmaceuticals, and STCube Pharmaceuticals; consulting fees from XRAD Therapeutics; travel grants from AstraZeneca; advisory fees from AstraZeneca and Merck; and stock or stock options from SEEK Diagnostics. MA reports research funding from Genentech, Nektar Therapeutics, Merck, GlaxoSmithKline, Novartis, Jounce Therapeutics, Bristol Myers Squibb, Eli Lilly, Adaptimmune, Shattuck Lab, and Gilead; consulting fees from GlaxoSmithKline, Shattuck Lab, Bristol Myers Squibb, and AstraZeneca; honoraria from AstraZeneca, Nektar Therapeutics, and the Society for Immunotherapy of Cancer; and advisory fees from Nanobiotix-MDA Alliance, and Hengenix. JWW reports grant funding from Alkermes, Nanobiotix, Merck, GlaxoSmithKline, Checkmate Pharmaceuticals, Varian, Bristol Myers Squibb, Reflexion, Artidis, Takeda, Gilead, HotSpot Therapeutics, and Kiromic; travel grants from Ventana, Aileron, Nanobiotix, Varian, and Reflexion; advisory fees from Alpine Immune Sciences, Reflexion, Aileron, Molecular Match, OncoResponse, Checkmate Pharmaceuticals, and Marvu Pharmaceuticals; a consultant role for Alpine Immune Sciences, Reflexion, Merck, Molecular Match, OncoResponse, Checkmate Pharmaceuticals, Marvu Pharmaceuticals, Incyte, Nanobiotix, Aileron, GI Innovation, Legion Healthcare, Roche, and Ventana Medical Systems; and stock options in Alpine Immune Sciences, Reflexion, Legion Healthcare, Molecular Match, OncoResponse, and Nanorobotix. IIW reports research funding from 4D Molecular Therapeutics, Adaptimmune, Adaptive Biotechnologies, Akoya Biosciences, Amgen, Bayer, EMD Serono, Genentech, Guardant Health, HTG Molecular Diagnostics, Lovance Biotherapeutics, Johnson & Johnson, Karus Therapeutics, MedImmune, Merck, Novartis, OncoPlex Diagnostics, Pfizer, and Takeda; personal fees from Asuragen, Genentech/Roche, Bristol-Myers Squibb, AstraZeneca/MedImmune, HTG Molecular, Merck, Guardant Health, Oncocyte, Daiichi-Sankyo, Pfizer, and Bayer; and consulting fees from Asuragen, Genentech/Roche, Bristol-Myers Squibb, AstraZeneca/MedImmune, Bayer, GlaxoSmithKline, Guardant Health, HTG Molecular Diagnostics, Merck, MSD Oncology, OncoCyte, Novartis, Flame, Pfizer, Regeneron, Merus, G1 Therapeutics, and AbbVie. ZL reports grant funding from the National Institutes for Health and National Cancer Institute (5 R01 HL157273-03 and P01 CA261669). JVH reports research funding from Bristol-Myers Squibb; and advisory fees from Bristol-Myers Squibb. All other authors declare no competing interests.

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References

    1. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015;16:630–637. - PMC - PubMed
    1. Chang JY, Mehran RJ, Feng L, et al. Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery. Lancet Oncol 2021;22:1448–1457. - PMC - PubMed
    1. Ball D, Mai GT, Vinod S, et al. Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. Lancet Oncol 2019;20:494–503. - PubMed
    1. Sun B, Brooks ED, Komaki R, et al. Long-term outcomes of salvage stereotactic ablative radiotherapy for isolated lung recurrence of Non-Small Cell Lung Cancer: A phase II clinical trial. J Thorac Oncol 2017;12:983–992. - PMC - PubMed
    1. Timmerman RD, Hu C, Michalski JM, et al. Long-term results of stereotactic body radiation therapy in medically inoperable stage I non-small cell lung cancer. JAMA Oncol 2018;4:1287–1288. - PMC - PubMed

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