Off label use of Mekinist (Trametinib)

[Graham49]

I came across this in chapter 43 of the Dr Mark Sholz book The Key to Prostate Cancer. It's only anecdotal evidence of course. Anybody considering taking it, should do it with agreement of their MO.

Mekinist is a Mek inhibitor and used to treat melanoma, thyroid cancer and non small lung cancer.

Patient Bill summarized from the book. Diagnosed late 2010 PSA 4.2 with Gleason 3+4, underwent surgery and upgraded to Gleason 4+5. PSA did not drop to zero. Radiotherapy but PSA only remained low for brief period. Lupron but resistance developed within year. Over next 3 years Provenge, Zytiga, Xtandi and Taxotere. By summer 2014 extensive in bone marrow. Xofigo started in Feb 2014. Became anemic and could only be kept alive with monthly blood transfusions. Xofigo stopped in August. PSA over 120. Bills chance of living another 6 months bleak. Started Mekinist. Bill purchased it at $10,000 per month. By December 2014 PSA had dropped to 18. Blood functioning again and did not need transfusions. He returned to full time work and took trips with family to Europe. Mekinist was well tolerated. Resistance eventually developed and cancer progressed and he succumbed in early 2016'.

Not a perfect ending but he got some extra quality time.

I searched for studies that might support the use of Mekinist for PCa and found a few papers. The best one is probably this.

MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer

Prostate cancer and prostatic diseases 22(4), 531-538, 2019

"ERK1 is the immediate downstream target of MEK1/2, which is druggable with trametinib, an approved therapeutic for melanoma."

The conclusions mention "an ongoing Phase II trial"

[cesces]

1. Thanks

2. Under what circumstances would you elect to use Mekinist in the place of, or addition to, more conventional therapy.

[Graham49 in reply to cesces]

I would probably have to be fairly desperate as Bill was. I will go along with SOC and supplements as long as it works and does not cause me much discomfort. I will then consider things like COC and other off label drugs. Mekinist is quite expensive, although not as expensive as when Bill was taking it. There is no generic trametinib yet.

[cesces in reply to Graham49]

But other than desperation, are there specific scenarios that specifically call out for the use of Mekinist?

[Graham49 in reply to cesces]

The science around MEK inhibitors and BRAF mutations is fairly new, so I look forward to new studies on this.

It appears that MEK inhibitors work best for cancers with BRAF mutations. There are also BRAF inhibitors such as dabrefenib. BRAF mutations are somatic and appear to be fairly rare (7%) for prostate cancer, if the 2020 study below is anything to go by.

Eradication of BRAF k601E mutation in metastatic castrate-resistant prostate cancer treated with Cabazitaxel and Carboplatin: A Case Report

This paper reports 2 cases with the mutation. Both progressed on hormonal treatments. One patient refused further chemotherapy after 6 doses of doceaxel and died. The other patient has had a prolonged and clinically meaningful response to Cabazitaxel and Carboplatin.