Immune Checkpoint Inhibitors in Patients With NSCLC and Brain Metastases

Immune checkpoint inhibitors (ICI) targeting PD-1 and PD-L1 are a standard treatment for metastatic non-small cell lung cancer (NSCLC) across multiple lines of therapy for patients who do not possess targetable driver mutations. While as many as 40% of patients with advanced NSCLC will develop brain metastases during the course of their disease, patients with brain metastases were often excluded from key trials of ICIs in NSCLC. A recently published retrospective analysis evaluated the efficacy of ICI in 1025 patients with NSCLC treated in 6 European centers, which included patients with brain metastases. Patients who received ICI in combination with chemotherapy and those with leptomeningeal metastases were not included in the analysis.

A total of 255 patients (24.9%) had brain metastases at the start of ICI treatment. Brain metastases were associated with younger patients, adenocarcinoma, performance status (PS) ³2, more frequent use of corticosteroids, and a higher median number of metastatic sites. Among patients with brain metastases, 39.2% had new and/or growing lesions (active), 14.3% were symptomatic, and 27.4% were receiving steroids. Disease-specific Graded Prognostic Assessment (ds-GPA) was known for 94.5% of patients. A score of 0-1, which indicates poor prognosis, was found in 35.7% of patients, and none of the patients had a score of 3.5-4, which is associated with best prognosis. Patients with lower ds-GPA more often used steroids.

At a median follow-up of 15.8 months from initiation of ICI therapy, there were no significant differences in objective response rate between patients with brain metastases and those without brain metastases (20.6% vs 22.7%; P = .484). The intracranial ORR was 27.3%, and the intracranial disease control rate (DCR) was 60.3%. Among the 23 patients with active brain metastases for whom PD-L1 expression information was available, PD-L1 expression ³1% was associated with an ORR of 35.7%, while those with PD-L1 of <1% had an ORR of 11.1%.

Median progression-free survival (PFS) was 1.7 months in patients with brain metastases, compared to 2.1 months in patients without brain metastases (P = .0009). Median PFS for patients with ds-GPA 0-1, 1.5-2.5 and 3 was 1.4 months, 2.4 months, and 5.5 months, respectively. Among patients with brain metastases, brain progression was more common in patients with active metastases compared to those with stable metastases (54.2% vs 30%; P<.001). The median OS was 8.6 months and 11.4 months for patients with and without brain metastases, respectively (P = .035). Median OS was 4.4 months for patients with ds-GPA scores of 0-1, which was significantly shorter than the 13.7 months seen in both patients with ds-GPA 1.5-2.5 (P<.001) and those with ds-GPA 3 (P = .010). Previous cranial radiotherapy was not associated with PFS and OS. A multivariate analysis identified corticosteroid use as a factor predicting for poorer OS in patients with brain metastases, while stable metastases and higher ds-GPS score were both associated with prolonged survival. Presence of brain metastases was not identified as a factor associated with poorer survival on ICI.

The investigators concluded that presence of brain metastases does not influence response or survival on ICI therapy for patients with NSCLC, and these agents can be successfully used in this population. Best outcomes on ICI for patients with brain metastases are in those with stable metastases and good ds-GPA scores. The authors also stressed that patients with untreated brain metastases, a good ds-GPA classification, and no need for corticosteroids, should not be excluded from clinical trials.

J Thorac Oncol. 2019 Feb 16. [Epub ahead of print.]
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