Trametinib Represents a ‘Major Advance’ for Rare Ovarian Cancer Subtype

February 10, 2022
Colleen Moretti
Colleen Moretti

Colleen Moretti, Assistant Editor for CURE®, joined MJH Life Sciences in November 2020. Colleen is a graduate of Monmouth University, where she studied communication with a focus in journalism and public relations. In her free time, she enjoys learning to cook new meals, spending time with her adopted beagle, Molly, or sitting on the beach with a good book. Email her at cmoretti@curetoday.com

The MEK inhibitor trametinib should be considered a new standard of care for patients with a rare subtype of ovarian cancer, explains an expert from The University of Texas MD Anderson Cancer Center.

Trametinib may improve survival compared with standard of care, which include chemotherapy or endocrine therapy, in patients with recurrent low-grade serous carcinoma compared to standard of care, according to recent data.

The MEK inhibitor, trametinib, resulted in a 13-month progression-free survival (time during and after treatment when the patient lives without disease progression) compared to standard of care at 7.2 months.

Dr. David M. Gershenson, lead author on the study and professor of gynecological oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center in Houston, explained that the number of effective therapies for this rare ovarian cancer subtype is limited, and these results highlight a new option for standard of care.

“It should definitely be considered one of the standard-of-care options, not the only one. The response rate of 26% and the significantly improved median progression-free survival, there’s no other drug that we’re currently using for recurrent low-grade serous carcinoma (that) is producing identical or even similar results,” he said in an interview with CURE®.

Patients in this trial were assigned to received either trametinib (130 patients) or physician’s choice of standard of care (130 patients).

Additional results from the trial, which were published in The Lancet, demonstrated an objective response rate (the rate of a measurable response to treatment) of 26% with trametinib compared with 6% with standard of care. Of note, 59% of patients assigned trametinib had stable disease for at least eight weeks.

Median overall survival was 37.6 months with trametinib and 29.2 months with standard of care. Gershenson mentioned that although this was not statistically different, there will be updated data to come focused on this. In addition, the median duration of response was 13.6 and 5.9 months, respectively.

“The number of effective therapies for this rare subtype is limited,” he added. “Chemotherapy is an option, and there are a number of chemotherapy drugs, but low-grade serous carcinoma, although it’s not totally insensitive or resistant, it’s not as sensitive to chemotherapy. There are a number of endocrine therapy drugs that are available, but MEK inhibitors offer a targeted or precision approach that is very important. If you really look at the results of this trial, we can see that trametinib should really be a new standard of care for these patients.”

The most common severe side effects with trametinib included skin rash (13%), anemia (13%), high blood pressure (12%), diarrhea (10%), nausea (9%) and fatigue (8%). Gershenson mentioned that many patients in this trial did require a dose reduction because of side effects, primarily for those who developed a skin rash.

“Side effects can be tricky.I would say this is not an easy drug to manage,” he said.

He explained that if a patient’s physician does not have experience with trametinib, they may want to seek out another physician who does, especially since it is commonly used in patients with melanoma.

Trametinib is not currently approved by the Food and Drug Administration for this setting; however, it is on the National Comprehensive Cancer Network Compendium. This means that these patients still have access to trametinib and most insurance plans will cover it, Gershenson explained.

“We've not had much of a problem since it did appear on the compendium. Because it has such good efficacy, it's one of the priority options for women who have a recurrence,” he added.

Gershenson concluded that the challenge now is to build on these results, and there are some ongoing trials in this space. In the meantime, he said that findings from this trial may greatly impact this patient population.

“I this this represents a major advance in the treatment of this rare (cancer) subtype,” he concluded.

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