In older or frail patients with stage III non-small cell lung cancer (NSCLC), undergoing reduced radiotherapy (RT) followed by sequential chemo-immunotherapy results in survival outcomes similar to standard RT, indicating its utility in vulnerable populations, suggests a study.
“However, because the study was not powered for noninferiority, we cannot conclude that the two regimens are equivalent,” the researchers said.
Between 30 September 2022 and 30 April 2024, 56 older/frail patients with stage III NSCLC ineligible for concurrent chemoradiotherapy (cCRT) were enrolled in this phase II randomized, open-label, two-cohort trial at a tertiary hospital in China.
Progression-free survival (PFS), the primary endpoint, was estimated using the Kaplan‒Meier method. Other endpoints assessed included overall survival (OS), objective response rate (ORR), and safety.
All patients received at least one dose of the study treatment in the intention-to-treat set. At 1 year, PFS was 84.3 percent (95 percent confidence interval [CI], 70.3‒98.3) in the standard RT group and 70.7 percent (95 percent CI, 54.3‒87.1) in the reduced RT group. [PLoS Med 2026;23:e1005111]
In the per-protocol set that included 53 patients, PFS at 1 year was 82.9 percent (95 percent CI, 68.9‒98.8) in the standard RT group and 73.4 percent (95 percent CI, 58.3‒92.4), with a median follow-up of 24 months.
Safety analysis revealed reduced grade 3/4 adverse events (AEs) with reduced RT relative to standard RT (53.6 percent vs 71.4 percent). One patient (3.6 percent) who received reduced RT and three patients (10.7 percent) treated with standard RT experienced grade 5 AEs.
Unfit patients
“To contextualize these results, it was helpful to view current treatment options for ‘cCRT-unfit’ patients as a spectrum of intensity and efficacy,” the researchers said.
“At one end are regimens for patients deemed unfit for any chemotherapy, such as RT alone followed by consolidation immunotherapy (SPIRAL-RT) or durvalumab after radiotherapy (DUART),” they added. [Eur J Cancer 2023;195:113373; ESMO Open 2025;10:105560]
These strategies put premium on tolerability, with reported median PFS ranging from 9 to 11 months.
At the other end is the PACIFIC-6 paradigm, wherein patients received standard sequential CRT plus durvalumab consolidation in a similarly defined ‘unfit’ population. In this study, 12-month PFS was 49.6 percent with a favourable safety profile. [J Thorac Oncol 2022;17:1415-1427]
The current study explores an intermediate-intensity approach, in which patients received sequential chemo-immunotherapy plus RT concurrently with ICIs. This approach was aligned with that of the DOLPHIN trial but involved prior systemic therapy. [JAMA Oncol 2023;9:1505-1513]
“This positions our reduced-dose RT regimen (50 Gy) as a potentially viable option on this spectrum, offering a balance between the robust efficacy of combined modality therapy and the imperative for reduced toxicity in a frail cohort,” the researchers said.
However, the current study was limited by its noncomparative design, small sample size, and lack of power to establish either superiority or noninferiority.