Clinically meaningful improvements in longer-term quality of life were achieved with the addition of atezolizumab immunotherapy to chemoradiation in patients with limited-stage small cell lung cancer (LS-SCLC), according to patient-reported outcome findings from the NRG LU005 trial presented during the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract LBA 08).
“While this study was not randomized between twice-daily vs once-daily radiation, these quality-of-life findings suggest that, relative to once-daily radiation, twice-daily radiation is associated with quality-of-life advantages from the patient perspective,” stated study Quality-of-Life Chair Benjamin Movsas, MD, Medical Director of Henry Ford Cancer, and Chair of Radiation Oncology at Henry Ford Health in Detroit.
Background and Study Analyses Methods
The phase III NRG LU005 trial enrolled 544 patients who were randomly assigned to receive standard chemoradiotherapy of platinum/etoposide every 3 weeks for four cycles plus thoracic radiotherapy at 45 Gy twice daily or 66 Gy daily starting with the second cycle of chemotherapy with or without atezolizumab every 3 weeks for a year starting with the second cycle of chemotherapy.
Results of the primary endpoint analysis, which were presented at the 2024 ASTRO Annual Meeting, showed that the addition of atezolizumab did not lead to an improvement in overall survival over chemoradiotherapy alone in patients with limited-stage small cell lung cancer. However, an exploratory analysis from the study did show a survival benefit for twice-daily vs daily radiotherapy of 35.4 months vs 28.3 months, respectively. But the difference in received radiation doses was not subject to randomization.
Patient-reported outcome analyses were planned to explore how the regimens impacted quality of life. Patient-reported outcome tools included FACT-TOI, EQ-5D-5L for quality-adjusted survival, and PROMIS-Fatigue. These measurements were administered at baseline; after chemoradiotherapy; and at 3, 6, 16, and 21 months after chemoradiotherapy. Clinically meaningful declines were defined as a 5-point decline from baseline in FACT-TOI.
PRO Findings
At baseline, compliance with patient-reported outcome questionnaires was over 85% and was 60% to 68% through 21 months after chemoradiotherapy. Higher completion rates correlated with better baseline performance status and pulmonary function.
During chemotherapy, declines in FACT-TOI were observed in both arms. However, they improved by 3 months after treatment and remained stable or improved from baseline levels by 6 to 21 months after treatment.
At 21 months, fewer patients in the added atezolizumab arm had clinically meaningful declines in FACT-TOI than in the standard chemoradiotherapy alone arm (25% vs 38%). Quality-adjusted survival measurements were similar in both treatment arms. PROMIS-Fatigue showed that immunotherapy did not increase fatigue levels.
Twice-daily radiotherapy, which was received by about 50% of all patients, was associated with better quality-of-life metrics than daily radiotherapy at all timepoints assessed. Clinically meaningful declines were significantly lower with twice-daily radiotherapy at the end of chemoradiotherapy (36% vs 60%), at 15 months (28% vs 41%), and at 21 months (22% vs 39%).
Multivariable assessment showed that twice-daily radiotherapy, cisplatin use, and immunotherapy were all significant predictors of lower, clinically meaningful declines.
Disclosure: The study was supported by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit amportal.astro.org.
