NRG-LU005 Trial: Immunotherapy Fails to Improve Survival in Limited-Stage SCLC
Results from the international clinical trial NRG-LU005, led by NRG Oncology and the Alliance for Clinical Trials in Oncology, were published in the Journal of Clinical Oncology.
The trial concluded that immunotherapy given concurrently with and after chemoradiation did not improve survival for participants with limited-stage small-cell lung cancer (SCLC).
Key Findings of NRG-LU005
The NRG-LU005 trial did not achieve its primary endpoint. The addition of the immunotherapy agent atezolizumab to chemotherapy and radiation did not significantly enhance survival for individuals with limited-stage SCLC.
While concurrent immunotherapy with chemoradiotherapy did not improve survival, it also did not lead to worsened outcomes or unexpected safety concerns.
Dr. Helen J. Ross, co-principal investigator of LU005 and Alliance lead investigator
An important associated finding from the study indicated that twice-daily radiation therapy was linked to improved survival within this patient population.
Radiation Therapy Observations
Radiation in the study was administered either once or twice daily, based on investigator choice. Analysis of the radiation fractionation schedule provided indirect evidence suggesting that twice-daily radiation therapy may influence outcomes positively.
Clinical trials from the 1990s previously indicated that twice-daily radiation therapy could improve survival for limited-stage SCLC patients. Despite this evidence, its adoption in the U.S. remains low.
Trial Design and Outcomes
Historically, management of limited-stage SCLC has relied on concurrent chemotherapy and radiation therapy. While immunotherapy has shown benefits for extensive-stage SCLC, its efficacy in earlier, potentially curable stages was unconfirmed prior to LU005.
The LU005 study enrolled 544 patients between May 2019 and December 2023 across 218 sites in the United States and Japan. Participants were randomized to receive either:
- Standard concurrent chemoradiation alone
- Chemoradiation plus atezolizumab intravenously every three weeks
Thoracic radiation schedules included 45 Gy administered twice daily over three weeks, or 66 Gy administered once daily over six-and-a-half weeks.
The addition of atezolizumab did not improve progression-free or overall survival.
- Median overall survival: 36.1 months in the chemoradiation-alone arm and 31.1 months in the chemoradiation plus atezolizumab arm.
- Median progression-free survival: 11.4 months for chemoradiation alone and 12.1 months for the atezolizumab group.
Both treatment arms exhibited survival outcomes that surpassed those of earlier landmark trials in this population. The 36.1-month median overall survival in the standard chemoradiation arm is among the longest reported in a randomized study for individuals with limited-stage SCLC.
Strong Validation for Twice-Daily Radiation
The study observed a consistent survival benefit associated with twice-daily radiation therapy. Despite decades of supporting evidence, routine adoption of this regimen is low, partly due to logistical challenges.
In LU005, twice-daily radiation was associated with substantially better survival than once-daily radiation, irrespective of immunotherapy use.
Specifically, in the chemoradiation-alone arm, patients receiving once-daily radiation had a 51% higher risk of death compared to those treated twice daily. A similar trend favoring twice-daily radiation was noted in the atezolizumab arm.
"LU005's findings, supported by contemporary trial methodology and stringent quality assurance, provide strong modern validation that 45 Gy delivered twice daily should remain the preferred thoracic radiation schedule for patients with limited-stage SCLC."
Dr. Helen J. Ross