Biomarkers may help identify lung cancer patients who benefit most from perioperative immunotherapy

UT MD Anderson Research News August 12, 2026

• Phase 3 CheckMate 77T trial demonstrated improved outcomes from immunotherapy given before and after surgery, called perioperative immunotherapy
• Patients receiving nivolumab before surgery were nearly twice as likely to have no detectable tumor DNA in their blood at the time of surgery
• Patients with cleared tumor DNA also were more likely to achieve a pathologic complete response, meaning no viable cancer was present in tumor and lymph nodes at the time of surgery

HOUSTON, AUGUST 12, 2026 ― Biomarkers including circulating tumor DNA (ctDNA) clearance and molecular residual disease (MRD) status may help identify which patients with resectable non-small cell lung cancer (NSCLC) get the greatest benefit from immunotherapy given before and after surgery (perioperative), according to new research led by The University of Texas MD Anderson Cancer Center.

The study, published today in Nature analyzed biomarkers and clinical outcome data from the Phase 3 CheckMate 77T trial, which previously demonstrated improved outcomes with perioperative immunotherapy. The researchers found that the best indicators of a positive outcome were ctDNA clearance before surgery and achieving a pathologic complete response, meaning no remaining cancer was detected at surgery.

“Perioperative immunotherapy has transformed care for many patients with resectable lung cancer, but we still need better markers to understand who benefits most from treatment,” said Tina Cascone, M.D., Ph.D., associate professor of Thoracic/Head and Neck Medical Oncology. “These results suggest that monitoring ctDNA before surgery may provide important insights into treatment response and long-term outcomes, bringing us closer to more personalized approaches.”

Why are biomarkers important in resectable lung cancer?
Patients with resectable NSCLC often face a substantial risk of recurrence after surgery. Therefore, researchers have been investigating whether biomarkers can help identify residual disease earlier and predict which patients are most likely to experience long-term benefits from immunotherapy.

ctDNA consists of fragments of tumor DNA that can be detected in a blood sample. A reduction or disappearance of ctDNA during treatment may indicate that therapy is eliminating cancer cells. Conversely, the presence of ctDNA after treatment can indicate the presence of MRD, meaning cancer cells remain in the body but are not detectable by conventional methods.

In this study, researchers evaluated ctDNA dynamics, MRD status and tumor genomic alterations in 190 patients enrolled in the CheckMate 77T trial.

What are the other key findings of the study?
In this study, patients who received chemotherapy plus nivolumab treatment were nearly twice as likely to have ctDNA clearance before their surgery compared with those in the chemotherapy plus placebo group (66% vs. 38%). The study also found that patients who received nivolumab were more likely to have a pathologic complete response at surgery compared to those who were treated with placebo (50% vs. 12%).

Researchers also found that patients who remained MRD-negative following surgery had better outcomes. All patients with detectable MRD after surgery experienced cancer recurrence, suggesting that MRD may serve as an early indicator of cancer recurrence.

Patients whose tumors harbored genetic alterations typically associated with poor outcomes, including alterations in the KEAP1, STK11, CDKN2A and SMARCA4 genes, also appeared to benefit from perioperative nivolumab. These patients were able to clear ctDNA, undergo surgery and achieve complete responses, suggesting that perioperative immunotherapy may provide benefit even among patients whose tumors harbor these higher-risk genetic alterations.

What are the implications for future lung cancer treatment?
After more than three years of follow-up, nivolumab continued to improve event-free survival compared with placebo without compromising patients' quality of life. The findings suggest blood-based biomarkers such as ctDNA clearance and MRD may help doctors better monitor treatment response and identify patients at higher risk of recurrence. However, this was an exploratory study, and additional research is needed before these tools can be routinely used in clinical practice.

***

This study was funded by Bristol Myers Squibb. A full list of collaborating authors and disclosures can be found with the full paper in Nature.