Pembrolizumab Shows Benefit for NSCLC Patients with Brain Metastases


The results showed that even patients with disease that has spread to the brain should be considered for immunotherapy.

Patients with non-small cell lung cancer (NSCLC) with brain metastases demonstrated similar survival benefit to those without when treated with pembrolizumab (Keytruda), according to study findings presented at the International Association for the Study of Lung Cancer (IASLC) 2019 North America Conference on Lung Cancer.

The results showed that even patients with disease that has spread to the brain should be considered for immunotherapy, said Lova Sun, MD, from the University of Pennsylvania, in an interview with CancerNetwork. Data showing how well immunotherapy works for non-small-cell lung cancer (NSCLC) that is metastatic and has spread to the brain is limited, since most clinical trials exclude such patients.

“We hypothesized that, similar to patients with (metastatic) NSCLC without brain metastases, patients with brain metastases may also benefit from pembrolizumab therapy, even though they were excluded from prior trials,” said Sun. “We were trying to show that brain metastases should not be a contraindication to pembrolizumab therapy, since these patients did just as well as patients without brain metastases.”

In the retrospective single-center study 239 patients were treated at the University of Pennsylvania between 2013 and 2017, and all were diagnosed with metastatic NSCLC. The median age was 65 years, and it was evenly split between males and females. Adenocarcinoma accounted for 164 (69%) of the cases. The majority (n = 209; 87%) were former or current smokers.

The primary outcomes were progression-free survival (PFS) and overall survival (OS), based on Kaplan-Meier methodology.

Pembrolizumab was given as a first-line treatment in 134 (56%) of the cases. Fifty-nine of the patients (44%) received pembrolizumab monotherapy and 75 (56%) received pembrolizumab in combination with chemotherapy.

Just 66 (28%) of the patients had brain metastases at baseline. Among those, the brain metastases were locally pretreated in 32 (48%) of those cases, split between stereotactic radiosurgery (n = 24; 75%), whole brain radiotherapy (n = 6; 19%), or surgical resection (n = 2; 6%). Patients with brain metastases were more likely to have adenocarcinoma and be never-smokers.

Next-generation sequencing (NGS) of the baseline tissue DNA were available for 172 (72%) of the patients. Mutations in TP53 (39%), KRAS (27%), and EGFR (8%) were identified.

The median follow-up, at the time of the data cutoff at the end of 2018, was 15 months.

Between the brain metastases and non-brain metastases groups, there was no difference in the median PFS (9.0 vs. 7.9 months; HR, 0.93, P = .7) and OS (18 vs. 21 months; HR, 1.03, P = .8).

Sun said there were clinical implications that could be drawn from the findings. She and the other researchers hope to investigate outcomes in other patients with metastatic NSCLC treated with other immunotherapy agents, as well as different treatment strategies, looking at factors including timing of local therapy in relationship to systemic therapy.

“The major clinical implication/benefit is that patients with brain metastases should be considered for immunotherapy; i.e. that brain metastases should not be considered a contraindication to immune therapy even though they were often excluded from clinical trials,” she said. “Again, we hope this data lends support to the clinical practice of considering and using immune therapy in (metastatic) NSCLC patients with brain metastases who were historically excluded from clinical trials.”


Sun L, Davis C, Marmarelis M, et al. Outcomes of Patients with Metastatic Non-Small-Cell Lung Cancer (MNSCLC) with Brain Metastases Treated with Pembrolizumab. Presented at: IASLC 2019 North America Conference on Lung Cancer; October 12, 2019; Chicago, Ill. Abstract OA03.02.

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