Adding immunotherapy to radiation did not help early-stage lung cancer survival

Adding the immunotherapy atezolizumab to stereotactic radiotherapy did not improve survival for people with high-risk, early-stage lung cancer who could not have surgery, according to the phase 3 SWOG/NRG S1914 trial published in The Lancet [s1]. The trial was stopped early for futility [s1].

Stereotactic body radiation therapy (SBRT) — high, precisely targeted radiation doses delivered in a handful of sessions — is the standard of care for early-stage non-small-cell lung cancer (NSCLC) in patients who are medically inoperable or decline surgery [s1]. Immunotherapy that unleashes the immune system against tumours has transformed the treatment of advanced lung cancer, and a natural question has been whether giving it earlier, around the time of radiation, could improve cure rates in early-stage disease [s1]. S1914 is the first fully reported phase 3 cooperative-group trial to test that idea in inoperable early-stage NSCLC [s1].

What the trial did

S1914 was a multicentre, open-label, phase 3 randomised trial that enrolled patients from 146 institutions across the United States [s1]. Eligible patients had T1-T3N0M0 NSCLC no larger than 7 cm, were medically inoperable or had declined surgery, and had at least one risk factor suggesting a higher chance of recurrence [s1]. They were randomly assigned to SBRT over three to eight fractions, either alone or with up to eight cycles of neoadjuvant, concurrent and adjuvant atezolizumab given at 1,200 mg intravenously every 21 days, with radiation beginning at the third cycle [s1]. The primary objective was to compare overall survival between the groups, and the trial was registered as NCT04214262 [s1][s2].

What it found

Between 25 March 2020 and 9 September 2024, 417 patients were enrolled and randomly assigned — 210 to atezolizumab plus SBRT and 207 to SBRT alone — of whom 402 were eligible and formed the main analysis population, 201 in each group [s1]. Their median age was 72.8 years, 54% were female and 46% were male [s1].

Accrual was closed at the first interim analysis for futility, with 76 progression events and 41 deaths among 400 eligible participants [s1]. An updated analysis, with 140 progression events, 92 deaths and a median of 24.8 months of follow-up among living patients, confirmed the picture: the overall-survival hazard ratio was 1.04 (95% confidence interval, 0.69 to 1.58; one-sided P=.58), meaning no survival advantage from adding the drug [s1]. Estimated two-year overall survival was 82% in both groups (95% confidence interval, 75 to 87) [s1].

The addition of immunotherapy did add harm. Grade 3 or higher adverse events occurred in 12% of patients given atezolizumab plus SBRT, against 3% with SBRT alone, and there were two grade 5 — that is, fatal — respiratory events in the atezolizumab group [s1].

How to read it

The result is a clean negative: a hazard ratio sitting almost exactly at 1.0, with a confidence interval that includes both meaningful benefit and meaningful harm, and identical two-year survival curves [s1]. Layered on top is a real increase in serious toxicity, including two treatment-era deaths from respiratory events in the immunotherapy arm [s1]. A futility stop at interim analysis means the trial's own monitors judged that continuing was unlikely to reveal a survival benefit [s1].

Funding deserves to be stated plainly. The trial was supported by the US National Institutes of Health and the National Cancer Institute — public funders — together with Genentech, the company that makes atezolizumab [s1]. That a cooperative-group trial with industry co-funding returned, and published, a firmly negative result is itself worth noting: the design and the public sponsorship did their job.

The findings are specific. They describe an older, medically inoperable population, a particular atezolizumab schedule wrapped around radiation, and early-stage disease [s1]. They do not speak to immunotherapy given in other settings or on other schedules, where separate trials continue [s1]. And the trial was open-label, though survival is an outcome that blinding cannot bias [s1].

Why it matters

The pull to extend a class of drugs that has worked spectacularly in advanced cancer into earlier disease is strong, and often justified — but not always. S1914 shows that, in this setting, adding atezolizumab to SBRT does not help patients live longer and does expose them to more harm [s1]. For now, SBRT alone remains the standard for high-risk, inoperable early-stage NSCLC [s1].

For contrast in how targeted lung-cancer therapies can succeed, see our coverage of ivonescimab in EGFR-mutated NSCLC.

This article describes trial results and is not medical advice. Treatment decisions are for patients and their treating clinicians.

Sources

• Induction and consolidation atezolizumab with SBRT versus radiation alone in high-risk, early-stage NSCLC (SWOG/NRG S1914) — The Lancet, 6 September 2026 (primary trial report)
• A Randomized Phase III Trial of Atezolizumab + SBRT Versus SBRT Alone in High Risk, Early Stage NSCLC, NCT04214262 — ClinicalTrials.gov, U.S. National Library of Medicine (trial registration)