Immunotherapy given during and after chemoradiation did not improve survival for study participants with limited-stage, small-cell lung cancer (SCLC) according to the results of an international clinical trial, NRG-LU005 , led by NRG Oncology in collaboration with the Alliance for Clinical Trials in Oncology. The results are published in the Journal of Clinical Oncology.
The trial did not meet its primary endpoint as the addition of the immunotherapy agent atezolizumab to chemotherapy and radiation did not significantly improve survival for those with limited-stage SCLC. However, twice-daily radiation therapy was associated with improved survival in this population.
“We are still learning how best to use immunotherapy in limited-stage, small-cell lung cancer. Concurrent immunotherapy with chemoradiotherapy did not improve survival, but we did not find worsened outcomes or unexpected safety signals,” said Helen J. Ross, MD, Professor of Medicine and Director of Research and Clinical Trials at Rush Cancer Center in Chicago, who served as co-principal investigator of LU005 and the Alliance lead investigator.
“Radiation was given either once or twice daily based on investigator’s choice. Although not randomized, our analysis of the radiation fractionation schedule provides indirect evidence that twice-daily radiation therapy may make a difference in outcomes,” Dr. Ross added. “Clinical trials dating to the 1990s showed that twice-daily radiation therapy can improve survival for patients with limited-stage SCLC, but only about 20 percent of patients in the U.S. receive this approach.”
Management of limited-stage, small-cell lung cancer has historically relied on chemotherapy delivered concurrently with radiation therapy. While immunotherapy has improved treatment for extensive-stage SCLC, at the time LU005 was developed, it remained unknown whether moving immunotherapy into earlier, potentially curable stages would offer benefit.
The LU005 study was designed to address this question, while also ensuring rigorous radiation quality assurance and broad patient eligibility. Importantly, unlike previous trials that enrolled only patients who completed chemoradiation without progression, LU005 allowed enrollment after a single cycle of chemotherapy, capturing real‑world patients earlier and ensuring that radiation plans could be centrally reviewed.
LU005 enrolled 544 patients between May 2019 and December 2023 across 218 sites in the United States and Japan. Participants were assigned to receive either standard concurrent chemoradiation alone or chemoradiation plus atezolizumab intravenously every three weeks starting with the first study cycle, which was the second cycle of chemotherapy.
Thoracic radiation was delivered using one of two schedules: 45 Gy administered twice daily over three weeks, or 66 Gy administered once daily over six-and-a-half weeks. The primary endpoint of the study was overall survival, with key secondary endpoints including progression‑free survival, distant metastasis‑free survival, objective response rate, local control, and safety.
The addition of atezolizumab did not improve progression-free or overall survival. The median overall survival was 36.1 months in the chemoradiation‑alone arm and 31.1 months in the chemoradiation plus atezolizumab arm. Median progression‑free survival was 11.4 months for chemoradiation alone and 12.1 months for the atezolizumab group. Both arms demonstrated survival outcomes that exceeded those of earlier landmark trials in this population. The 36.1‑month median overall survival in the standard chemoradiation arm represents one of the longest survival outcomes ever reported in a randomized study in people with limited-stage SCLC.
An interesting finding in LU005 was the consistent survival benefit associated with twice‑daily radiation therapy. Even though twice‑daily radiation is supported by decades of evidence, adoption of the regimen in routine practice remains low, partially due to logistical challenges for patients, caregivers and providers. In LU005, while the choice of fractionation was left to the treating investigators, twice‑daily radiation was associated with substantially better survival than once‑daily radiation, regardless of immunotherapy use.
In the chemoradiation‑alone arm, patients receiving once‑daily radiation had a 51 percent higher risk of death compared to those treated twice daily. A similar trend favoring twice‑daily radiation was also observed in the atezolizumab arm.
“By combining contemporary trial methodology, a robust sample size, and stringent quality assurance requirements, LU005 provides one of the strongest modern validations that 45 Gy delivered twice daily should remain the preferred thoracic radiation schedule for patients with limited-stage SCLC,” Dr. Ross said.
In addition to Rush University, investigators on the study included researchers from the City of Hope in Atlanta; City of Hope National Medical Center in Duarte, Calif.; Dana-Farber/Harvard Cancer Center in Boston; Duke University Medical Center in Durham, N.C.; Emory University Winship Cancer Institute in Atlanta; First Health of the Carolinas/SCOR NCORP in Pinehurst, N.C.; Henry Ford Cancer Institute in Detroit; Heartland NCORP in Springfield, Ill.; Johns Hopkins University in Baltimore; Marshfield Clinic Health System in Weston, Wis.; MD Anderson Cancer Center in Houston; Miami Cancer Institute/Baptist Health South Florida in Miami; NRG Oncology Statistics and Data Management Center in Philadelphia; Rutgers Cancer Institute in New Brunswick, N.J.; Saitama Medical University International Medical Center in Yamane, Hidaka City, Japan; The Ohio State University Comprehensive Cancer Center in Cleveland; Trinity Health Cancer Center in Ann Arbor, Mich.; UCSF Medical Center in San Francisco; University Hospitals Seidman Cancer Center and Case Western Reserve University Medical Center in Cleveland; University of Maryland Greenebaum Cancer Center in Baltimore; University of Rochester in Rochester, N.Y.; University of Pennsylvania in Philadelphia; Virginia Commonwealth University in Richmond; and the American College of Radiology in Philadelphia.
This study was supported by grants from the National Cancer Institute and Genentech.
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References: Journal of Clinical Oncology : Chemoradiation ± Atezolizumab in Limited-Stage Small-Cell Lung Cancer: Results of NRG Oncology/Alliance LU005
NRG/Alliance LU005 : Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab
The Alliance for Clinical Trials in Oncology is a national leader in advancing cancer research, uniting more than 25,000 cancer specialists at 115 main institutions and 1,400 affiliates across the U.S. and Canada. As part of the National Clinical Trials Network and a leading research base for the NCI Community Oncology Research Program, the Alliance conducts pioneering, practice-changing clinical trials that improve outcomes and reshape standards of care. Its work has led to multiple FDA approvals, influenced national guidelines, and produced hundreds of high-impact publications. More than 40,000 participants have taken part in Alliance studies, and its growing biospecimen repository now includes more than 1.5 million samples, collected over the past 30 years. Learn more at www.AllianceforClinicalTrialsinOncology.org .
Journal of Clinical Oncology
Randomized controlled/clinical trial
People
Chemoradiation ± Atezolizumab in Limited-Stage Small Cell Lung Cancer: Results of NRG Oncology/Alliance LU005
13-Jan-2026
Chemoradiation ± Atezolizumab in Limited-Stage Small Cell Lung Cancer: Results of NRG Oncology/Alliance LU005 The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Kristin A. Higgins Employment: city of hope Stock and Other Ownership Interests: Picture Health Consulting or Advisory Role: AstraZeneca, Reflexion Medical, Janssen, Daiichi Sanyko Research Funding: Reflexion Medical, Jazz Pharmaceuticals Travel, Accommodations, Expenses: AstraZeneca Chen Hu This author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Consulting or Advisory Role: Johnson & Johnson Enterprise Innovation Inc, Belay Diagnostics LLC, Health Catalyst Helen J. Ross Consulting or Advisory Role: GlaxoSmithKline, AstraZeneca, IDEOlogy Health Research Funding: Roche (Inst) Salma K. Jabbour Consulting or Advisory Role: Merck Sharp & Dohme, AstraZeneca, Radialogica, Advarra Research Funding: Merck Sharp & Dohme (Inst), NCI (Inst), Beigene (Inst), Guardant Health (Inst), Haystack Oncology (Inst) Expert Testimony: deichert Travel, Accommodations, Expenses: Merck, AstraZeneca David E. Kozono Consulting or Advisory Role: Genentech Taofeek K. Owonikoko Stock and Other Ownership Interests: Cambium Medical Technologies, Taobob LLC, GenCart, Coherus Biosciences Consulting or Advisory Role: Novartis, Abbvie, Eisai, G1 Therapeutics, Takeda, Bristol Myers Squibb, MedImmune, BerGenBio, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Bayer, Merck, Jazz Pharmaceuticals, Ipsen, Eisai, Roche/Genentech, Janssen, Exelixis, BeiGene, Triptych Health Partners, Daichi, Coherus Biosciences, Heat Biologics, Puma Biotechnology, Xcovery, Meryx Pharmaceuticals, Gilead Sciences Research Funding: Novartis (Inst), Bayer (Inst), Regeneron (Inst), AstraZeneca/MedImmune (Inst), Abbvie (Inst), G1 Therapeutics (Inst), Bristol Myers Squibb (Inst), Corvus Pharmaceuticals, Amgen (Inst), Loxo/Lilly (Inst), Pfizer (Inst), Incyte (Inst), Merck (Inst), Oncorus (Inst), GlaxoSmithKline (Inst), Calithera Biosciences (Inst), Roche/Genentech (Inst), Meryx Pharmaceuticals (Inst), Boehringer Ingelheim (Inst), Bayer (Inst), Cardiff Oncology (Inst), Puma Biotechnology (Inst), Daiichi Sankyo/Astra Zeneca (Inst), Ymabs Therapeutics Inc (Inst) Patents, Royalties, Other Intellectual Property: Overcoming Acquired Resistance to Chemotherapy Treatments Through Suppression of STAT3 (Inst), Selective Chemotherapy Treatments and Diagnostic Methods Related Thereto (Inst), DR4 Modulation and its Implications in EGFR-Target Cancer Therapy Ref:18089 PROV (CSP) United States Patent Application No. 62/670,210 June 26, 2018 (Co-Inventor) (Inst), Soluble FAS ligand as a biomarker of recurrence in thyroid cancer; provisional patent 61/727,519 (Inventor) (Inst) Travel, Accommodations, Expenses: AstraZeneca, Janssen Other Relationship: Roche/Genentech, EMD Serono, Novartis Uncompensated Relationships: Reflexion Medical Open Payments Link: https://openpaymentsdata.cms.gov/physician/253457 Timothy A. Ritter Employment: VCU Terence M. Williams Employment: City of Hope Honoraria: Reflexion Medical Speakers' Bureau: Reflexion Medical Research Funding: RefleXion Medical (Inst) Patents, Royalties, Other Intellectual Property: Albumin-bound chemotherapies developed at the Ohio State University (patent pending) Travel, Accommodations, Expenses: Reflexion Medical James Welsh Employment: MD Anderson Cancer Center Stock and Other Ownership Interests: MolecularMatch, Alpine Immune Sciences, Checkmate Pharmaceuticals, Nanorobotix, Oncoresponse, Reflexion Medical, Reflexion Medical, Welsh DV8, OligoImmune Honoraria: Nanobiotix, Reflexion Medical, Alpine Immune Sciences, Varian Medical Systems Consulting or Advisory Role: Reflexion Medical, Checkmate Pharmaceuticals, Nanorobotix, Oncoresponse, Nanobiotix, Genentech, Kezar Life Sciences, Novocure, McKesson Speakers' Bureau: Accuray, Taiwan Lung Cancer Society, The Radiosurgery Society, Roche Molecular Diagnostics, McKesson/US Oncology Network Research Funding: Bristol Myers Squibb, Nanobiotix, Artidis, Reflexion Medical, Takeda, Hotspot Therapeutics, Gilead Sciences, Kiromic, Novocure, Genentech, Bayer, Varian Medical Systems, SciClone, Nurix Patents, Royalties, Other Intellectual Property: MolecularMatch, MP470 (amuvatinib), MRX34 regulation of PDL1, XRT technique to overcome immune resistance Travel, Accommodations, Expenses: IASLC, AACR, Shandong Cancer Hospital, Turkish Society of Lung Cancer, Aileron Therapeutics, MedAustron, Reflexion Medical, Gustave Roussy Cancer Center, Radiation Research Society, Nanobiotix, The Korean Society for Radiation Oncology, American Society for Radiation Oncology, Ventana Medical Systems, Artidis Jeffry P. Simko Stock and Other Ownership Interests: Protean Biodiagnostics, Alpenglow biosciences, Triopsy Medical Inc Consulting or Advisory Role: Uro-1 Research Funding: Intuitive Surgical (Inst) B Movsas Employment: Henry Ford Hospital Stock and Other Ownership Interests: biolife, Abbvie, Acrivon Therapeutics, metlife, United Therapeutics Research Funding: Philips Healthcare (Inst), Siemens/Varian (Inst) Patents, Royalties, Other Intellectual Property: Lung phantom for image guidance, MR-CT imaging related patent for radiation oncology Travel, Accommodations, Expenses: Alpha Tau, Siemens Healthineers Kyoichi Kaira Speakers' Bureau: AstraZeneca, Ono Pharmaceutical, Bristol-Myers Company, Chugai Pharma Research Funding: AstraZeneca/Daiichi Sankyo (Inst) Amit K. Gupta Stock and Other Ownership Interests: Moderna Therapeutics, Revolution Medicines Pranshu Mohindra Employment: University Hospitals Cleveland Medical Center, University Hospitals Cleveland Medical Center (I) Travel, Accommodations, Expenses: IBA Proton Therapy, Inc Open Payments Link: https://openpaymentsdata.cms.gov/physician/942373 Jeremy Brownstein Honoraria: AstraZeneca, DAVA Pharmaceuticals, MDoutlook Consulting or Advisory Role: Varian Medical Systems Stephen Chun Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Nektar, National Cancer Institute Travel, Accommodations, Expenses: AstraZeneca Rupesh Kotecha Honoraria: Elekta, BrainLAB, Novocure, Telix Pharmaceuticals, InSightec, GT Medical Technologies Consulting or Advisory Role: Novocure, GT Medical Technologies Speakers' Bureau: Novocure, GT Medical Technologies (I) Research Funding: Medtronic (Inst), Blue Earth Diagnostics (Inst), Novocure (Inst), GT Medical Technologies (Inst), AstraZeneca (Inst), Exelixis (Inst), ViewRay (Inst), BrainLAB (Inst), Cantex Pharmaceuticals, Inc (Inst), IBA (Inst), Kazia Therapeutics (Inst) Travel, Accommodations, Expenses: Elekta, Novocure, BrainLAB, GT Medical Technologies Other Relationship: GT Medical Technologies Data Safety Monitoring Board, Plus Therapeutics Data Safety Monitoring Board, InSightec Advisory Board Thomas E. Stinchcombe This author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript. Consulting or Advisory Role: Takeda, Gilead Sciences, Coherus Biosciences, Boehringer Ingelheim, Pfizer, Janssen Oncology Research Funding: Seagen (Inst), Mirati Therapeutics (Inst), Nuvalent, Inc (Inst), Boehringer Ingelheim (Inst) Travel, Accommodations, Expenses: Pfizer Other Relationship: GlaxoSmithKline, Genentech, Merck, Pfizer Jeffrey D. Bradley Employment: University of Pennsylvania Abramson Cancer Center Honoraria: Mevion Medical Systems Consulting or Advisory Role: Mevion Medical Systems Travel, Accommodations, Expenses: AstraZeneca Uncompensated Relationships: Genentech, IBA No other potential conflicts of interest were reported.