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Jump to Key Points A 6-year follow-up of patients with early-stage non-small cell lung cancer (NSCLC) treated with the addition of immunotherapy to stereotactic ablative radiotherapy (I-SABR) provides possible evidence of a survival benefit with the treatment approach in this population.
This is a follow-up to the phase 2, randomized I-SABR trial, which included patients with early-stage NSCLC who had been treated with four doses of nivolumab immunotherapy in addition to SABR. It showed overall survival (OS) and sustained event-free survival (EFS) rates that were significantly higher than those in patients treated with SABR alone. Additionally, the researchers saw low rates of grade 3 toxicities related to nivolumab.
“The take-home message for me is that the addition of immunotherapy to SABR is a very promising approach, but we need to wait for positive phase 3 trials before this will change the practice,” said Ben Slotman, MD, PhD, discussant in the session, where the new results were presented at the American Society for Radiation Oncology (ASTRO) 2026 Annual Meeting.
Joe Y. Chang, MD, PhD, corresponding author of I-SABR and thoracic radiation oncologist and professor of radiation oncology in the Department of Radiation Oncology, The University of Texas (UT) MD Anderson Cancer Center in Houston, presented the new OS and EFS findings at the meeting.
- Early-stage NSCLC: I-SABR improved 6-year OS 69% vs 55% with SABR alone.
- 6-year EFS also higher with I-SABR: 55% vs 32%.
- Nivolumab + SABR showed benefit after adjustment for age, sex, tumor size.
- Grade 3 nivolumab-related AEs occurred in 15%; no grade 3 pneumonitis or grade ≥4 toxicity.
- Lower second primary lung cancer rate with I-SABR: 4.5% vs 16%.
While SABR has been the standard of care in the treatment of inoperable early-stage NSCLC, regional as well as distant relapses are common with the treatment, occurring in as many as 42% of patients, the study authors report. Due to increasing evidence suggesting synergistic effects between radiotherapy and immunotherapy, including in the treatment of later-stage NSCLC, the authors evaluated the addition of the PD-1 inhibitor nivolumab in patients with treatment-naive NSCLC who had no distant or regional recurrence.
The patients were randomly assigned to treatment with either SABR alone (n = 75) or SABR plus once-monthly nivolumab 480 mg administered over four doses (n = 66). Exclusion criteria for the study included prior treatment with immune checkpoint inhibitors or contraindications to SABR or immunotherapy.
In the study’s primary analysis, at a median of 33 months, the 4-year EFS rate was 53% vs 77% in the SABR group vs the I-SABR group (hazard ratio [HR], 0.38; P = .0056 in the per-protocol population, and HR, 0.42; P = .0080 in the intention-to-treat population). The OS data at the time of the primary analysis were not mature.
While there were no grade-3 or higher adverse events (AEs) in the SABR group, 10 patients (15%) in the I-SABR group experienced grade 3 immunologic AEs related to nivolumab, with no cases of grade 3 pneumonitis or grade 4 or higher toxicity.
In the current study, the 6-year rate of EFS was 55% vs 32% with I-SABR vs SABR alone (P = .0018). Higher EFS with I-SABR was also seen after adjusting for sex, age, tumor size, and other factors. Significantly greater OS was also seen with I-SABR, with a rate of 69% vs 55% with SABR alone (P = .0214), including after adjustment for sex, age, and tumor size (HR, 0.514; P = .0239).
A further subgroup analysis consistently showed better OS with I-SABR across the board, including among younger patients, smokers, those with different SABR regimens, and those with no previous lung cancer. In other outcomes, rates of the development of a second primary lung cancer were lower among those treated with I-SABR than among those treated with SABR alone (4.5% vs 16%).
“We already have excellent results with SABR alone, so the question is which patients need [the addition of immunotherapy] most,” said Slotman, who is a professor and a chair of the Department of Radiation Oncology at Amsterdam University Medical Center in Amsterdam, Netherlands.
“Some studies have shown that the combination of SABR and immunotherapy can lead to increased toxicity, so we have to be cautious,” he added.
The I-SABR trial received funding from Bristol Myers Squibb and the UT MD Anderson Cancer Center Alliance, and the National Cancer Institute at the National Institutes of Health through a Cancer Center Core Support Grant and Clinical and Translational Science Awards to UT MD Anderson Cancer Center. Chang and Slotman had no disclosures to report.
