An exploratory analysis in operable lung cancer links the disappearance of detectable tumour DNA from blood to longer event-free survival, supporting further study of relapse-risk markers.
Patients whose tumour DNA became undetectable in blood had longer event-free survival in an exploratory analysis from the NeoCOAST-2 lung cancer trial. The association suggests a possible way to assess relapse risk, but does not show that DNA clearance itself caused better outcomes.
Patients with non-small-cell lung cancer that can be removed surgically remain at high risk of relapse despite treatment around surgery. The peer-reviewed report, published in Nature on 25 October 2026, examines whether blood and tissue responses can help distinguish patients with different risks.
NeoCOAST-2 is a randomised phase 2 platform trial, a design that tests several treatment combinations. It enrolled patients with operable stage IIA–IIIB non-small-cell lung cancer and tested treatments given around surgery. Each of the three reported groups received standard chemotherapy and durvalumab, an antibody targeting the PD-L1 protein, plus a different additional drug.
This report gives the first results for two secondary outcomes specified in advance: event-free survival and circulating tumour DNA clearance. Event-free survival measures time without events defined by a trial, such as relapse. Circulating tumour DNA, or ctDNA, is tumour-derived DNA in the bloodstream; clearance means it becomes undetectable by the test, not proof that all cancer has disappeared.
| Trial group | Additional drug | Patients | 24-month event-free survival | ctDNA clearance | Pathological complete response |
|---|---|---|---|---|---|
| Arm 1 | Oleclumab | 76 | 70.5% | 50.9% | 20.3% |
| Arm 2 | Monalizumab | 72 | 75.7% | 54.5% | 25.7% |
| Arm 4 | Datopotamab deruxtecan (Dato-DXd) | 54 | 77.9% | 72.5% | 35.2% |
The Dato-DXd combination had the highest numerical event-free survival and tissue-response rates. The authors say those results warrant further evaluation; they do not establish that this combination is superior to the others.
Analysis
Across the reported groups, patients with ctDNA clearance had longer event-free survival than those without clearance: the pooled hazard ratio was 0.22, with a 95% confidence interval of 0.11–0.45. A hazard ratio compares how quickly events occur during follow-up; a value below 1 favours the clearance group. It is a relative comparison, not an absolute increase in the percentage of patients surviving.
The researchers also examined pathological complete response, or pCR: no remaining cancer detected in tissue examined after treatment. Patients with both ctDNA clearance and pCR had more favourable event-free survival than those with neither response, with a hazard ratio of 0.10 and a 95% confidence interval of 0.02–0.42.
These links between test responses and later outcomes were exploratory, unlike the secondary outcomes specified before the analysis. The authors suggest that assessing blood clearance and tissue response together may improve risk stratification—sorting patients into groups with different risks of relapse.
Several authors have affiliations with AstraZeneca’s oncology research and development teams, including Lara McGrath and Gozde Kar. The published abstract gives no safety findings, so the response and survival figures alone cannot establish the balance of benefits and harms for these combinations.
The findings also do not establish that choosing treatment on the basis of the combined blood and tissue results improves patient outcomes. The authors call for further evaluation of the Dato-DXd combination; whether the combined response measures can guide treatment remains an open clinical question.
The NIH–NASA competition seeks better measurements in laboratory drug-safety models, with submissions scheduled to open on 15 December 2026.
2 min
The programme brings together national laboratories, universities and industry partners, with plans for a sensor-equipped test bed and self-adjusting pilot production lines.
2 min
Previously seen only through its infrared heat, the dusty feature is visible in reflected starlight, allowing researchers to test a possible collision origin.
4 min
