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PIK3CA mutation linked to brain metastases in large cell neuroendocrine carcinoma

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PIK3CA mutation defined a distinct phenotype of large cell neuroendocrine carcinoma of the lung characterized by brain metastases, according to study results presented at the International Association for the Study of Lung Cancer World Conference on Lung Cancer.

Genomic characterization of large cell neuroendocrine carcinoma — an aggressive form of non-small cell lung cancer — has revealed several putative oncogenic drivers. However, the clinical relevance of these drivers is largely unknown.

Mian Xie , MD, PhD, physician-in-chief at Guangzhou Medical University in Guangdong, China, and colleagues conducted comprehensive genomic profiling — which including next-generation sequencing — of 68 patients with stage IV large cell neuroendocrine carcinoma of the lung to analyze differences in the clinical characteristic between patients with KRAS (n = 15; median age, 72 years) and PIK3CA (n = 15, median age, 65 years) mutations, the two major disease subtypes. The other patients (median age, 69 years) had different mutations.

Results showed patients with PIK3CA mutations had more aggressive disease. These patients had shorter median OS (7.9 months vs. 18.6 months; P = .002), greater metastatic burden (> 3 organs, 15.2% vs. 4.7%; P = .029) and greater incidence of brain metastases (19% vs. 2.3%; P = .001).

Researchers then conducted whole-exome sequencing of paired lung primaries and brain metastases from four patients. These analyses showed that the primary tumor gave rise to brain metastases that harbored PIK3CA mutations.

Pictilisib (GDC-0941, Genentech), a PI3K inhibitor, induced significant tumor growth inhibition in a large cell neuroendocrine carcinoma of the lung xenograft model with PIK3CA mutation.

“The result may be relevant for targeted therapy and prophylaxis of NSCLC brain metastases,” the researchers wrote.” – by Alexandra Todak

Reference:

Xie M, et al. Abstract JCSE 01.15. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Oct. 15-18, 2017; Yokohama, Japan.

Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of reporting.