Reference Detail

Ref Type

Journal Article

PMID

(27388325)

Authors

Casadei Gardini A, Chiadini E, Faloppi L, Marisi G, Delmonte A, Scartozzi M, Loretelli C, Lucchesi A, Oboldi D, Dubini A, Frassineti GL, Ulivi P

Title

Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report.

Journal	Vol	Issue	Date	Pages	Journal Short Title
BMC cancer	16		2016 Jul 07	429	BMC Cancer

URL

Abstract Text

Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug.Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity.Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF G469V	lung non-small cell carcinoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with synchronous BRAF wild-type hepatocellular carcinoma (HCC) and non-small cell lung cancer harboring BRAF G469V demonstrated a partial response in primary lung lesions, complete response in the lung metastasis, and stability of the HCC following treatment with Nexavar (sorafenib) (PMID: 27388325).	27388325