New BRAF/MEK inhibitors coming to market

[Lisa Kottschade]

I am curious what your practices might be doing in terms of choice of therapy with a 3rd in class BRAF/MEK inhibitor combo likely coming to market very soon? What factors would sway you to one product over another?

Also- do you think this will help to drive down cost of these oral agents?

Looking forward to everyone’s insights.

[Virginia Seery]

I hate to say it, but we tend to start the combination that we are most familiar with – dabrafenib/trametinib. However, if someone develops side effects, we certainly think about vem/cobi.
Factors that would sway me to switch would be a better side effect profile and improved efficacy. It looks like the data for encorafenib and binimetinib will meet those qualifications so it is very exciting.

I suspect a third combination will help bring down the costs of these meds as they each look to protect or gain their market share. What a whirlwind for new drug approvals in melanoma! It is exciting and challenging all at the same time.

[Mollie Reed]

We tend to be creatures of habit as well and really only look to switch to other BRAF-MEK combos if there might be decreased incidence of side effects. For example, if someone has horrid fevers from Taf-Mek, we’ve tried Vem-cobi. I do believe that this newer (third) combo coming to market has a lower incidence of certain AEs with similar efficacy, so it can likely find its place and be utilized. And I hope that competition will help control costs -always an issue and one we deal with so commonly with oral meds.

[Kathleen Madden]

Well said ladies, I certainly echo your points on the clinical decsision making. It is going to be great to have another option to enable continuation of therapy. Somtimes this can be confusing for patients, in justifying a switch of therapy, I usually use the analogy of changing blood pressure medications such as a betablocker, within the same category, that usually helps as that analaogy tends to be relatable.

Additionally, I think the role of pt support programs can play a role of initial choice of therapy.

[Krista Rubin]

Glad we are all on the same page.
Cost/copay is another to consider. The more competition, the better the prices. So hopefully more on the market means more patients are able to afford what can be astronomical copays in some cases.

I will say, however, my experience with the investigational BRAF/MEKi (encorafenib + binimetinib) has been quite positive. My understanding is this combo has not seen the pyrexia as the others are. IF indeed true, this would be a notable & important difference and may very much sway usage.

[Rajni Kannan]

Has anyone heard an update on when the FDA will be approving these medications? We have a few patients whose Pyrexia on danrafenib and tramatenib is really signicant and even with various interventions we are not able to keep them consistently on drugs.

[Krista Rubin]

Totally agree Rajni. The pyrexia can be a HUGE issue.

The FDA has until June 16th to make final decision…however, the rumor mill suggests within a month we may have new options!

[Kathleen Madden]

Rumor mill update- hearing that early June is when the new combo therapy will be available. Behind the scenes sounds very ready for launch and immediate availability of meds for pts. That’s what I am hearing.

[Krista Rubin]

Exciting news that encorafenib + binimetinib were FDA approved yesterday for metastatic melanoma with an identified BRAF v600E/K mutation. This combination has SIGNIFICANTLY less pyrexia than other regimens (notably D + T), and also has the added benefit if minimal photosensitivity over vemurafenib. For those patients intolerant of dabrafenib + trametinib due to pyrexia, they now have an opportunity to switch to enco/bini and hopefully, be able to stay on the meds.

One other advantage is both enco and bini can be taken with OR without food! That makes scheduling so much easier for patients.

[Rajni Kannan]

We were so excited to hear about the approval! We have had several patients who have been waiting for the approval due to intolerability with Dabrafenib and Tramatenib. We just now need to wait for insurance to update their system to be able to get access to these drugs. The main issue is going to be the same as we see with the other targeted therapies which is high copays for our patients with Medicare part D. Finding sources or assistance programs to help with patients donut holes is always difficult.

[Kathleen Madden]

We have transitioned about 8 patients from other braf / mek agents to the Braf-tovi & Mek-tovi & they are doing very well in regard to tolerablitliy and not having reoccurrences of the AE’s that were dlt’s & drug holds on prior therapies.
Have you transitioned any patients?
How are patients doing on BRAFtovi & Mektovi?
Thoughts on how you will proceed with starting BRAF/ Mek therapies as we move forward?

[Mollie Reed]

This was such exciting news. We haven’t taken anyone off of their current BRAF/MEK therapy, but if they develop side effects, we will certainly consider transitioning them to another. Also, we will certainly consider this combo front line now depending upon the patient circumstances.

[Kathleen Madden]

Any one else transition patients from tag/mek or zelb/cobi over to braf/mek-tovi?
So far the paients that we transitioned are all doing quite well. there are 2 patients who have had stroing GI toxicities & flu like sx within a month of starting tx who required drug holiday & dose reduction after 2 attempts to restart full dose & they are doing better on the reduced dose.

[Kathleen Madden]

This past week I have had 2 more patients on Braf/Mek- tovi’s experience febrile toxicities preceeded by several days of mild anorexia. While the drugs were placed on hold, some of the symptoms proceeded to get worse or persist about 3-5 days later, I am attributing this to the long half life. Febrile work ups have been negative, no other clinical sx of infection. Low dose steroids have been most effective for these cases.
Next step plan is to get to back to baseline & dose reduce & restart.
Any similar experiences?

[Suzanne McGettigan]

Hi Kathy–
Yes, I have a few patients who were switched from an alternate BRAF/MEK combination to encorafenib/binimetinib who have experienced fever, flu like symptoms, complex pyrexia. I have utilized the processes that we have previously used and were recently published by the Australlian group including holding both therapies, starting with non-steroidal anti-inflammatories, but quickly moving to corticosteroids if not responding to the non-steroidal alternatives, or not effectively responding. Also, making sure that in this setting that patients are staying adequately hydrated with water as well as electrolyte rich beverages. Once they are fever free for ~ 48 hours, then resuming full dose.
I haven’t had to dose reduce anyone yet, but that may be coming.
I have had some patients experience GI side effects from these combo regimens. In my practice, it has seemed to wax and wane a little over the course of their therapy and has generally responded to anti-diarrheal and anti-emetic therapies temporarily.
Great discussion!
Suzanne

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