ASCO: Cleveland Clinic shares new ideas for targeted therapy of brain metastasis

At ASCO 2016, Cleveland Clinic researchers examined the impact of the number of brain metastases on overall survival for two common cancer types: Non-small cell lung cancer and gastroesophageal cancer.


Recent research on brain metastasis from two disparate primary malignancies (non-small cell lung cancer and gastroesophageal cancer) may impact patient care in each case. Abstracts presented by Cleveland Clinic researchers at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago this weekend communicated related findings.

“Brain metastases is a significant and serious complication of systemic cancers — 10 times more common than primary malignant brain tumors, so this is an important clinical problem we see in clinic every day,” said Dr. Manmeet Ahluwalia, director of Cleveland Clinic’s Brain Metastasis Research Program and a study author.

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In non-small-cell lung cancer brain metastasis, Ahluwalia said targeted therapies changed outcomes of certain patients. 

Historically, the number of BMs has been considered a key factor. And, in wild-type non-small cell lung cancer, patients who had one BM generally did better than those who had two-to-three, or four or more. However, emerging evidence suggests that, in some ways, BM in patients with mutations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) is different.

“We found in our cohort that the number of brain metastases did not impact the overall survival rate for NSCLC patients with activating mutations in the EGFR gene and the ALK gene,” Dr. Ahluwalia said in describing the study. This is contrary to the earlier knowledge where the number of brain metastases significantly impacts survival.

With IRB approval, Cleveland Clinic’s Neuro-Oncology Center database was used to identify patients treated between 2000 and 2014 for NSCLC BM with mutational status (EGFR/ALK/wild).

In the updated analysis for the ASCO meeting, researchers identified a total of 1,078 NSCLC BM patients treated in that time period. Among 348 with mutational analysis, 91 were positive for mutations.

Highlights from the results included:

  • Median overall survival for ALK and EGFR plus NSCLC BM was 19.93 months vs. 9.87 months for wild type.
  • The number of BMs in the mutation-positive group didn’t significantly impact overall survival, whereas fewer metastases in wild type had significantly better OS on multivariate analysis, excluding extracranial metastases.

“This analysis showed that in patients with EGFR- and ALK-positive lung cancer, the number of brain metastases did not impact survival,” Ahluwalia said. “The analysis also highlighted that the outcomes for patients with brain metastases with EGFR-positive and ALK-positive mutational status are significantly better than for patients who do not have these mutations.”

Recent National Comprehensive Cancer Network guidelines on NSCLC have been updated to reflect advancing knowledge with respect to EGFR-positive and ALK-positive disease, Ahluwalia said.

Ahluwalia and his co-authors also presented a second abstract on prognostic factors and outcomes in patients with BMs from gastroesophageal cancer. Although BM occurs in less than 4 percent of all tumors of the GI tract, the incidence of BM from gastrointestinal cancers may be rising, in part due to more effective systemic treatments and prolonged survival.

Not much is known about the outcomes of these patients, according to Ahluwalia. The Disease Specific Graded Prognostic Assessment — which is based solely on the KPS — is a commonly used prognostic index in patients with BM.

Cleveland Clinic’s Brain Tumor and Neuro-Oncology Center database was used to identify 63 gastroesophageal cancer patients who were treated between 2002 and 2014.

The main highlight from the study was that, on multivariate analysis, the number of brain metastases and the presence of symptoms were independent predictors of overall survival, in addition to KPS.

“This analysis of this research shows that there are a number of other factors which impact the outcomes of these patients that include a number of brain metastases, presence of lung or liver metastases and performance status,” Ahluwalia said.