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GNA11 Mutation: Consider MEK Inhibitors and Yervoy

You have indicated that your patient's tumor has a mutation in the GNA11 gene. The GNA11 gene is often mutated in uveal (eye) melanoma. The most common GNA11 aberration at codon 209 can activate the MAPK pathway (Van Raamsdonk, et al. 2010).

There are several potential treatment approaches to consider for your patient.

MEK inhibitor combinations are supported by preclinical studies. Combinations of MEK inhibitors with either PI3K or mTOR inhibitors have show efficacy in GNAQ- and GNA11-mutant melanomas (Ho, et.al, 2012, Khalili, et. al., 2012). MEK inhibition in combination with CDK2/CDK4 or Mdm2 inhibition has also been effective suppressing melanoma growth in preclinical studies (Jalili A, et al. 2012, Ji Z, et al. 2012). Trials are mounting this year testing these combinations in melanoma patients. Check the clinical trials table below.

Another option also supported by preclinical data involves inhibition of protein kinase c (PKC) with the PKC inhibitor, sotrastaurin (AEB071) (Wu, et. al., 2012).

Immunotherapy drugs may be a good treatment option to consider for your patient. These include the approved CTLA-4 inhibitor, Yervoy, the investigational PD-1 inhibitor, nivolumab (BMS-936558/MDX-1106), and the investigational PD-L1 inhibitor, BMS-936559. Results of a Phase 1 trial with BMS-936559 revealed long-lasting objective responses (6 to 17%) in 9 of 52 melanoma patients (Brahmer, et.al, 2012). Results of a trial with nivolumab revealed a positive impact on overall survival (1- and 2-year survival rates were 62 and 43% respectively) and long-lasting objective responses in 33 of 107 patients with advanced melanoma receiving nivolumab (Topalian, et al. 2014). Immunotherapy trials for this patient are included in the trials table below.

 References

Clinical Trials

Details of your patient's condition will determine eligibility for any specific trial. We encourage shared decision-making between patients and physicians.
The selected criteria return 60 trials.

ECOG score

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Potentially Relevant Drugs

Drug Other names Drug Target Manufacturer Status
The information above is selected based upon the information you provided and the guidance of our editorial board. It is not necessarily comprehensive and may not reflect information that is not publicly available. The specifics of your patient's situation may suggest options not included here, or may exclude some options that we have shown.
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