Nature Medicine retracts lung cancer trial over integrity concerns

Nature Medicine retracted a randomized phase 3 lung cancer trial, LungTIME-C01, on June 24. The paper studied 210 patients with treatment-naive stage III-IV non-small cell lung cancer at Hunan Cancer Hospital in Changsha, China, and tested whether sintilimab or pembrolizumab plus chemotherapy worked better when infused before 3 p.m. than later in the day.

The February 2 report drew wide attention for its chronotherapy claim in oncology. The early-treatment group had a median progression-free survival of 11.3 months, compared with 5.7 months in the later-treatment group, and a median overall survival of 28.0 months versus 16.8 months.

The retraction note cited substantial changes to the study registration on ClinicalTrials.gov, including inconsistently reported or modified endpoints, eligibility criteria, sample size and study design. It also flagged discrepancies between the original Chinese protocol and translated versions submitted to the journal. The translated protocol published with the manuscript was dated 2022 but cited studies from 2023 and 2024, and the authors called some changes administrative errors rather than prospectively documented amendments.

The source data raised statistical and procedural concerns. Randomization was performed on the day of treatment for almost all patients. Other red flags included an unusually smooth progression-free survival curve, no censoring in the first year, no adverse events leading to treatment discontinuation, similar immune-related adverse event rates despite very different efficacy, and deviations from fixed-calendar imaging schedules because of COVID-19 delays and cycle-based assessments.

Nature Medicine had already added a caution notice after publication and opened an investigation into the inconsistencies. The corresponding authors agreed with the retraction, while several other authors did not respond to the journal’s correspondence.