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Understanding Treatment of Leptomeningeal Disease in NSCLC


Researchers assessed treatment patterns and outcomes of patients with non-small cell lung (NSCLC) cancer and leptomeningeal disease exposed to osimertinib.

Recent study findings suggest prior exposure to osimertinib—an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor—may have favorable impacts on the natural history of leptomeningeal (LM) disease among patients with EGFR mutated non-small cell lung cancer (NSCLC) and LM disease.

Writing in Clinical Lung Cancer, researchers explained results also showed any systemic therapy after LM disease diagnosis was associated with longer survival and did not increase health care utilization. However, more research is warranted to determine if osimertinib-containing regimens confer a survival benefit after LM disease diagnosis among patients who received prior osimertinib, they said.

LM disease is associated with late NSCLC, confers a poor prognosis, and has been previously linked with EGFR mutated NSCLC as opposed to wild-type EGFR. It also affects between 9% and 10% of patients with the mutated disease. In the past, diagnostic challenges have hindered efforts to identify prognostic factors for LM disease.

Osimertinib is approved as first-line treatment for metastatic EGFR mutated NSCLC.

To better elucidate systemic treatment strategies and health care utilization in those with EGFR mutated NSCLC and LM disease, investigators assessed electronic medical record (EMR) data of 54 patients who received treatment at a single center in Seattle, Washington between January 2000, and March 2020.

Mean patient age at NSCLC diagnosis was 59 years while the majority of patients (70%) were female.

Analyses revealed:

Median time from NSCLC diagnosis to development of LM disease was 21.0 months (95% CI, 16.7-26.3 months)

Median time to LM disease diagnosis was 33.3 months (95% CI, 21.5-48.0 months) in patients that received osimertinib 80 mg daily at any time prior to LM disease development, vs 18.4 months (95% CI, 11.7-22.1 months) in those without osimertinib exposure before LM disease

Patients who received osimertinib 80 mg were more likely to have EANO ESMO type I LM disease (42% vs 11%; P <.05)

Radiographic appearance of LM disease was more likely to be mixed (42% vs. 31%) or linear (37% vs. 29%), and less likely to be nodular (0% vs. 26%) in patients that received osimertinib prior to LM disease (P = .20)

Patients that received any post-LM disease systemic therapy had a lower risk of death relative to those that did not (HR 0.17, P < .001), with a suggestion that osimertinib-containing regimens result in longer median overall survival

Emergency department, hospital and hospice utilization were not associated with receipt of post-LM disease systemic therapy

Overall, “data suggest that osimertinib favorably alters the natural history of LM disease toward a delayed, less symptomatic and less functionally compromising presentation.” However, “this also suggests that presentation of LM disease among patients on osimertinib can be subtle and thus difficult to diagnose,” authors added.

Future research is warranted to better understand the both the impact of post-LM disease systemic therapy on survival in this patient population and the optimal therapy regimen.

The observational nature of the study, in addition to its small sample size, mark limitations. In addition, although researchers assessed a 20-year time frame, osimertinib was only approved as a first-line treatment as of 2018. It was also challenging to capture clinically relative endpoints from the EMR data.

“Osimertinib given prior to the development of LM disease in EGFR mutated advanced NSCLC is associated with longer time to LM disease diagnosis, fewer symptoms and less functional compromise relative to other pre-LM disease systemic treatments,” researchers concluded.


Merkhofer CM, Eastman B, Densmore I, Halasz LM, McGranahan T, Baik C. Systemic treatment patterns and outcomes in patients with EGFR mutated non-small cell lung cancer and leptomeningeal disease. Clin Lung Cancer. Published online April 28, 2022. doi:10.1016/j.cllc.2022.03.013

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