Nature Medicine retracts lung cancer study on morning immunotherapy

Nature Medicine Springer Nature Group on Tuesday retracted a phase 3 clinical trial that reported patients with advanced lung cancer who received immunotherapy before 3 p.m. lived nearly a year longer than those treated later in the day — removing the only prospective evidence that time-of-day scheduling could improve immunotherapy outcomes.nature+2

The retraction of the LungTIME-C01 trial, led by Zhe Huang of Hunan Cancer Hospital in China, came after a four-month investigation prompted by concerns raised online shortly after the paper's February 2026 publication. The editors stated that "due to the amount and nature of the problems identified, the editors no longer have confidence" in the integrity of the results.medpagetoday+2

A Study That Drew Immediate Scrutiny

The trial, which randomized 210 patients with advanced non-small cell lung cancer to receive anti-PD-1 immunochemotherapy either before or after 3 p.m., reported hazard ratios of roughly 0.40 for both progression-free survival and overall survival — an effect size that many oncologists flagged as implausibly large. Median overall survival was 28 months in the early group versus 16.8 months in the late group.aaox2.substack+2

Within days of publication, researchers raised questions about statistical inconsistencies in the data. STAT News reported in February that Nature Medicine had opened an investigation into the paper. Critics noted that the effect size was larger than what is typically seen when comparing active immunotherapy to chemotherapy alone, let alone comparing two identical drug regimens given at different hours.medscape+2

Broader Implications for Chronotherapy

The retraction leaves the question of whether treatment timing matters for immunotherapy largely unresolved. A large propensity-matched analysis from the ETOP-Roche i-TIMES study, presented at the European Lung Cancer Congress in March 2026, found no survival difference between morning and afternoon immunotherapy administration across eight randomized trials.oncologynewscentral

"The current evidence is insufficient to support adopting early-time-of-day immune checkpoint inhibitor dosing in routine clinical practice," said Jeffrey Gray, one of the i-TIMES investigators, at the conference.oncologynewscentral

Oncologist Paolo Tarantino of Dana-Farber Cancer Institute wrote on X following the retraction: "The only prospective evidence that time-of-day matters for immunotherapy is now gone."x

Earlier retrospective studies had suggested a possible circadian effect on immunotherapy response, but none demonstrated the dramatic survival differences reported by the now-retracted trial. The retraction underscores the role of post-publication scrutiny in identifying problematic research, even in high-profile journals.medscape