Emily Graham, PharmD, MS, BCOP, an Oncology Clinical Pharmacy Specialist at Allegheny Health Network in Pittsburg, Pennsylvania, discusses the potential outcomes of mirvetuximab for patients with platinum-resistant ovarian cancer.
PT Staff: Mirvetuximab soravtansine-gynx (Elahere; ImmunoGen) was recently approved for platinum-resistant ovarian cancer. Can you briefly review what this drug is and its specific indication?
Emily Graham, PharmD, MS, BCOP: So I will just refer to it as mirvetuximab because that is a mouthful. It's a folate receptor alpha (FRα) targeted antibody drug conjugate. The monoclonal antibody portion is chimeric and it's directed against FRαthat is conjugated to small molecule anti-tubulin agent (DM4) which is a maytansine derivative. The antibody binds to the surface of cells expressing FRα, and then it's internalized and intracellularly releases DM4. That agent then disrupts the microtubules within the cell resulting in cell cycle arrest and apoptosis. Mirvetuximab is FDA-approved for patients with platinum-resistant cancer, as you mentioned, and they do have to be FRα-positive and have received 1 to 3 prior lines of systemic therapy.
So this population does include our epithelial ovarian fallopian tube and primary peritoneal cancer patients. And I think it's important to note that here, FRα-positivity is defined as 75% or more of cancer cells staining was 2-plus intensity on immunohistochemistry. So this positive overall result has to be confirmed prior to a patient starting on this drug.
PT Staff: Why is this indication so important?
Emily Graham, PharmD, MS, BCOP: This indication is important because prior to this, these pretreated platinum-resistant patients mostly just had single agent options that elicited response rates of less than 20%. So even combination regimens, such as those evaluated in the AURELIA trial looking at Bevacizumab plus single-agent chemotherapy, only evoked response in less than 30% of patients. Mirvetuximab was found to have an overall response rate (ORR) of about 32% in patients who were FRα-positive, and it's estimated that at least 35% of patients with ovarian cancer are, so this is very promising for this subgroup of our platinum-resistant patients who have been historically very difficult to treat.
PT Staff: The approval was based on results from the SORAYA study. Can you review some of the key highlights from these findings?
Emily Graham, PharmD, MS, BCOP: So SORAYA was a phase two single-arm trial that included patients with platinum-resistant ovarian fallopian tube and primary peritoneal cancers with high FRα expression that had received 1 of the prior lines of therapy. As the indication reflects, the primary endpoint was ORR, which I mentioned earlier, and it was found to be about 32%. They also observed 5 complete responses (CRs). Secondary endpoints included median duration of response (DoR), which was 6.9 months, median progression free survival (PFS), which was 4.3 months, and also overall survival (OS), which was 13.8 months. And then the FDA granted accelerated approval based on these findings from SORAYA. However, a confirmatory trial called MARISOL is currently ongoing.
PT Staff: Mirvetuximab does have some significant adverse effects. What should pharmacists know about these?
Emily Graham, PharmD, MS, BCOP: Some of the more common adverse effects (AEs) that we saw with mirvetuximab were fatigue, increased liver function, so aspartate transferase (AST) and alanine transaminase (ALTE), cytopenia, nausea, abdominal pain and constipation, peripheral neuropathy and pulmonary toxicity, as well as ocular toxicity, [which] has also occurred and were more serious. So that FRα is expressed throughout our eyes and this drug was found to be particularly toxic to eye tissues for that reason. And they even adjusted how doses were calculated to lessen these toxicities during their phase 1 studies. Even with this dose calculation adjustment, these ocular AEs were still found to occur and over 50% of patients, and some of which were grade 3—they included visual impairment, keratopathy or keratitis, dry eye, photophobia, and eye pain. It's important for us as pharmacists to know that the use of supportive therapy is a central throughout treatment.
PT Staff: In particular, why does it affect the eyes?
Emily Graham, PharmD, MS, BCOP: When they were just first developing this drug, they figured out very quickly that it was very toxic to the eyes since they did express so much of that (folate). They basically made it so that everybody would have a little bit of a lower dose. They were calculating it using actual bodyweight and now we're using this adjusted this version of adjusted bodyweight that makes our doses lower.
PT Staff: Why is supportive care so important for patients receiving this drug?
Emily Graham, PharmD, MS, BCOP: So supportive care is important because prevention is critical for some of these more serious AEs. There's a significant amount of eye care that must be initiated once a patient is started on mirvetuximab. Exams need to be done at baseline and then prior to every other dose for at least the first 8 cycles. And then corticosteroid and lubricating eyedrops such as prednisone and hypromellose are recommend throughout therapy, and the use of contacts even should be avoided.
On top of these ocular toxicities, this drug also has a risk of infusion-related reactions given the chimeric nature of the antibody. And it was also found to be moderately emetogenic. So it is recommended to pre-medicate with acetaminophen and Benadryl as well as a 5-hydroxytryptamine 3 (5-HT3) receptor antagonists and dexamethasone prior to each dose.
PT Staff: With such an intense drug and treatment regimen, how can pharmacists play an educational role with patients?
Emily Graham, PharmD, MS, BCOP: It's important for us, as you mentioned, to educate on signs and awareness of our AEs of interest, and to encourage patients to let their healthcare team know of anything new or worrisome is going on. The eye care can be especially cumbersome for people. Those prednisone eyedrops need to be used 6 times a day starting the day prior to treatment and continue through day 4 of each cycle. And then on days 5 through 8, patients need to install the drops for 4 times a day. On top of that, the lubricating drops are to be used 4 times a day and is needed. This schedule can be very confusing, and it requires a lot of education. I think too as pharmacists, we can serve as a good reference for the health care team as well. On the other components of AE prevention that go into this regimen, like the premedication for nausea and infusion-related reactions, this drug is also titrated to reduce that risk of reaction. Any assistance or education we can provide to nurses would be beneficial to patients so I think just appreciate knowing possibilities of what they can expect once they get started. And providing things such as our resources [and] such as a calendar and checklist to assist with the eye care regimen would probably be very helpful to them as well.
PT Staff: Is there anything you want to add?
Emily Graham, PharmD, MS, BCOP: Yes, 1 other thing I wanted to mention. Working in this field and with a lot of these patients with ovarian cancer, I did want to add that the SORAYA trial did include patients who had been previously treated with a poly (ADP-ribose) polymerase (PARP) inhibitor.
This is a question that comes up a lot for us because a lot of our currently available date on ovarian cancer did not include those people because these drugs are relatively new. So those patients that had prior PARP inhibitor in the SORAYA study did have a similar response rate to everyone else— that [was an] over 30% response rate. I think this is relevant to point out just given their frequency of use nowadays. For all my colleagues that work in thegynecologic oncology world, I wanted to mention that because I think it's a useful tip to know.