On April 19, 2016, the laboratory «Evrogen» sent a report with the results of the molecular profiling of the tumor. BRAF V600E mutation was detected. This disorder had a target therapy: BRAF inhibitors, but they were approved for another diagnosis: melanoma.
Nobody excluded me from the clinical trial. But I was in position where I didn’t have any obvious effect from pembrolizumab and there was «no more than a week» left until the irreversible terminal stage. At the same time a decrease in bilirubin level was acheived (!) due to successful stenting, and at least obstructive jaundice and intoxication from bilirubin receded. At the beginning of May 2016, Dr Valeriy V. Breder suggested not missing this «window of opportunity» in my condition and trying targeted therapy against the detected disorder. The decision was made in consultation with the tumor biologist Andrey R. Zaretskiy, who took into consideration the potential sensitivity of my tumor.
On May 18, 2016, I began targeted therapy with BRAF inhibitors. Despite the difficulties of the first days of taking the medicine, i.e. a sudden unexpected and a severe adverse side effect to ultraviolet, as a result, fever, high temperature, rash; the need for antibiotics, most likely due to the inflammatory process associated with the stent, that targeted therapy had an immediate positive effect. All tumors were reducing before our eyes.
An adverse reaction to ultraviolet occurred while I was taking vemurafenib, BRAF inhibitor (trade name Zelboraf), which I had to start with because dabrafenib, BRAF inhibitor (trade name Tafinlar) was not available in pharmacies. That adverse side effect to ultraviolet is typical of vemurafenib and is described in the package leaflet. I had to stop taking it due to severe rash and uncontrollable fever.
After switching to dabrafinib, the adverse side effects were managed, and my condition returned to normal. Dabrafinib was taken in combination with trametinib, MEK inhibitor (trade name Mekinist). That scheme was the initial goal of the targeted therapy.
Then there had to be taken certain steps in order «to convince» local Authorities of the Ministry of Health that the targeted therapy in my case was «not my personal experiments and creativity», but the treatment I needed. Six months later I was able to arrange the provision of the necessary drugs (see more detailed information below).
At the end of May 2016, I also sent a paraffin block with the tumor tissue to the American Foundation Medicine laboratory for test of 315 genes. They confirmed the presence of the BRAF V600E mutation and also found CDKN2A/B. I suspect that in 2016 I was one of the first Russian patients to send them tumor tissue for testing. Now the organizational process has become much simpler and more accessible, since there are Russian medical institutions and laboratories
that process documents and send biomaterials.
Then there was a long correspondence with the Moscow Department of Health about PET CT. Finally, on July 18, 2018, patients with cholangiocarcinoma were included in the Order for state-funded PET CT.
The stent placed in my bile ducts in April – May 2016 was removed in November 2016.
Currently, there are no evidence of disease progression. The targeted therapy was canceled due to serious adverse side effects to dabrafenib (fever, high temperature that was difficult to bring down, severe joint pains), these did not occur immediately, but after a complete response to the targeted therapy was achieved.