Reference Detail

Ref Type

Journal Article

PMID

(28514312)

Authors

Zick A, Peretz T, Lotem M, Hubert A, Katz D, Temper M, Rottenberg Y, Uziely B, Nechushtan H, Meirovitz A, Sonnenblick A, Sapir E, Edelman D, Goldberg Y, Lossos A, Rosenberg S, Fried I, Finklstein R, Pikarsky E, Goldshmidt H

Title

Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Medicine	96	20	2017 May	e6931	Medicine (Baltimore)

URL

Abstract Text

Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients. Here, we report a clinical service offering mutation detection of archived samples using the ion Ampliseq cancer panel coupled with clinical consultation.A multidisciplinary think tank consisting of oncologists, molecular-biologists, genetic counselors, and pathologists discussed 67 heavily pretreated, advanced cancer patient cases, taking into account mutations identified using ion Ampliseq cancer panel, medical history, and relevant literature.The team generated a treatment plan, targeting specific mutations, for 41 out of 64 cases. Three patients died before results were available. For 32 patients, the treating oncologists chose not to include the panel recommendation in the treatment plan for various reasons. Nine patients were treated as recommended by the panel, 5 with clinical benefit, and 4 with disease progression.This study suggests that routine use of massive parallel tumor sequencing is feasible and can judiciously affect treatment decisions when coupled with multidisciplinary team-based decision making. Administration of personalized based therapies at an earlier stage of disease, expansion of genetic alterations examined, and increased availability of targeted therapies may lead to further improvement in the clinical outcome of metastatic cancer 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
ATM mut NRAS Q61R	melanoma	predicted - sensitive	Binimetinib	Case Reports/Case Series	Actionable	In a clinical case study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312).	28514312
PIK3CA I391M	uterine cancer	predicted - sensitive	Sirolimus	Case Reports/Case Series	Actionable	In a clinical case study, a uterine cancer patient harboring PIK3CA I391M demonstrated stable disease when treated with Rapamune (sirolimus) (PMID: 28514312).	28514312
ABL1 G250R ABL1 G251D	oral cavity cancer	no benefit	Nilotinib	Case Reports/Case Series	Actionable	In a clinical case study, Tasigna (nilotinib) treatment resulted in no benefit in a patient with oral cavity cancer harboring ABL1 G250R and G251D (PMID: 28514312).	28514312
BRAF V600E TP53 Q192K	colon cancer	predicted - sensitive	Panitumumab + Vemurafenib	Case Reports/Case Series	Actionable	In a clinical case study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 28514312).	28514312
KIT D816V NRAS Q61R	melanoma	no benefit	Pembrolizumab + Trametinib	Case Reports/Case Series	Actionable	In a clinical case study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312).	28514312