How Is Oligoprogressive Disease Managed in Patients With EGFR-Positive NSCLC?

A recent study demonstrated that most patients with EGFR-positive (EGFR+) non-small cell lung cancer (NSCLC) who were treated with osimertinib did not receive local therapy despite presenting with oligoprogressive disease.

In addtion, the study showed that this occurred “regardless of age, number of sites, or mutational profile, although patients with longer time to progression on osimertinib were more likely to receive local therapy.”

Chelsea Lau, MD, of Northwestern University, and colleagues conducted the study and presented their findings during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting in Chicago, Illinois.

It was important to conduct the study because consideration of local therapy, either radiation or surgical resection, is recommended by National Comprehensive Cancer Network (NCCN) guidelines for patients with EGFR+ NSCLC who experience oligoprogressive disease while receiving treatment with osimertinib, but “the degree to which local therapy is used in oligoprogressive disease in current practice is not well described.”

To explore management strategies in this patient population, investigators performed a retrospective review of electronic medical records of 161 patients with metastatic EGFR+ NSCLC who received treatment at Northwestern Memorial Hospital between January 1, 2016, and January 1, 2025. Defining oligoprogressive disease as five lesions or less, they evaluated progression pattern, tumor genomics, and therapy prior to and following progression. Additionally, they employed Fisher’s exact test to assess the association between variables and therapeutic strategy.

The researchers identified 60 patients with oligoprogressive disease who were treated with osimertinib at the time of disease progression. At the time of progression, 53.4% of patients underwent a change in systemic therapy without local therapy, and among these patients, 58.1% transitioned to treatment without osimertinib. Furthermore, 13.8% of patients with oligoprogressive disease were reported to have a change in systemic therapy in addition to receiving local therapy.

Among the 24.1% of patients who received local therapy (50% stereotactic body radiotherapy, 43% stereotactic radiosurgery of the central nervous system, 7% surgical resection) without a change in systemic therapy, the mean time to change in systemic therapy after local therapy was reported as 10.3 months (95% CI, 5.0-15.6).

The investigators also highlighted that patients with time to disease progression on osimertinib of 24 months or more were “significantly more likely to receive local therapy without change in systemic therapy (41.6% vs 19.6%; P=0.02).” In addition, the researchers observed that age, number of sites, and tumor genomics, including EGFR mutation, had no significant impact on therapeutic strategy.

In reflecting on the results, the investigators emphasized that “local therapy in oligoprogressive disease in EGFR+ NSCLC has been associated with improved outcomes, but current implementation may be limited.”

“While our study is limited as a single center analysis, our results suggest further study is needed for evidence-based guidelines development for local therapy implementation in oligoprogressive disease,” the researchers concluded.