Top Takeaways from ASCO: Brain metastases and genetic profiles

Brain metastases in non–small cell lung cancer, melanoma and breast cancer exhibit similar genetic landscapes with limited but important differences when compared with primary tumors, aligning more with a linear progression model of cancer metastasis, according to researchers.

The findings suggest primary tumors and brain metastases would respond to similar chemotherapeutics with consideration for blood-brain barrier penetration, with small molecule inhibitors of EGFR and topoisomerase inhibitors etoposide (VePesid, Bristol-Myers Squibb) or irinotecan (Camptosar, Pfizer) among the potential options to be particularly effective in treating brain metastases.

Santosh Kesari

“Using multiplex tumor profiling to compare brain metastases with the original tumors in non-small cell lung cancer, breast cancer and melanoma, we were able to reveal similarities and differences that potentially carry important therapeutic implications,” Santosh Kesari, MD, PhD, chair of the department of translational neuro-oncology and neurotherapeutics at John Wayne Cancer Institute at Providence Saint John’s Health Center in Santa Monica, Calif., told Healio.com. “These data provide rationale for selecting drugs for metastatic brain tumors based on molecular information from primary tumor data; however there were exceptions with several biomarkers in breast cancer.”

Kesari and colleagues profiled tumor samples using a multiplatform service (Caris Life Sciences) that analyzed sequencing, protein expression and amplification.

The investigation included 5,391 NSCLC (293 brain metastases and 5,098 lung), 3,595 breast cancer (99 brain metastases and 3,496 breast) and 761 melanoma (101 brain metastases and 660 skin) unpaired samples.

The researchers detected no substantial differences between brain metastases and primary tumor sites in 48 genes by looking at their mutations, with the exception of PIK3CA in breast cancer; this gene showed less mutation in brain metastases compared with breast samples (10% vs. 26%, P = .02).

Conversely, by using immunohistochemistry and in-situ hybridization to look at protein expression and gene amplification, respectively, brain metastases demonstrated greater expression of TOP2A, TOPO1 and TS, as well as EGFR amplification, compared with primary tumor sites.

“These findings are important because there are therapies that are available to target these aberrations, including etoposide, irinotecan, etc., that may be particularly relevant to treat cancers with brain metastases,” Kesari said.

He underscored the hypotheses warrant further investigation in clinical trials and may shed light on treatment choices for brain metastases.

“Larger prospective studies using paired specimens will be informative to confirm these findings,” Kesari said. – by Allegra Tiver

For more information: Kesari S, et al. Abstract 2060. Presented at: ASCO Annual Meeting. May 29-June 2, 2015; Chicago.

Disclosure: Kesari reports serving on an advisory board for Caris Life Sciences.