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Newly FDA-Approved Drug Elahare May Be Effective Treatment For Patients With A Particularly Aggressive Form Of Ovarian Cancer

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November 22, 2022

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Contributed by Dr. Muneeb Niazi, Medical Fellow at SurvivorNet.

 

  • Ovarian cancer cells commonly carry folate receptor alpha (FRα) protein on their surface. Up to 80% of new and recurrent ovarian cancers may carry this protein. Generally, FRα levels tend to be high in more aggressive ovarian cancers.
  • Oncologists can order FRα testing for their ovarian cancer patients through NeoGenomics at no cost; FRα can be targeted by the new drug, Elahare. It is a unique drug, which is part antibody, part chemotherapy.
  • Up to one-third of the patients receiving Elahare may experience a clinically meaningful reduction in the amount of ovarian cancer in their bodies. This effect may last for 6-7 months on average.
  • Common side effects associated with Elahare include fatigue, nausea, diarrhea, and visual disturbances. More rarely, significant damage to the eyes and lungs may occur. At least 1 death has been attributed to Elahare so far.

Ovarian cancer, especially when it is diagnosed at later stages, is especially difficult to treat. Part of the reason is that it can be resistant to traditional, platinum-based chemotherapies leaving patients with very few other treatment options. A newly FDA-approved drug, Elahare (mirvetuximab soravtansine) may offer hope to patients with such resistant cancers. Elahare, which targets the folate receptor alpha (FRα) protein present on the tumor cell surface, was tested in a rigorous clinical trial called SORAYA and showed effectiveness at suppressing cancer growth in at least one third of patients.

“This accelerated approval of mirvetuximab soravtansine for recurrent, platinum resistant, folate receptor alpha positive recurrent ovarian cancer is incredibly meaningful for patients who have this cancer,” says Dr. Ursula A. Matulonis, chief of the Division of Gynecologic Oncology at Dana-Farber and Co-Principal Investigator of the SORAYA study. “There have been no approved therapies for platinum resistant ovarian cancer since 2014, so today’s action by the FDA is a very significant milestone.”

An essential component of ovarian cancer treatment is platinum-based chemotherapy, such as carboplatin and cisplatin. 25% of women, however, have ovarian cancers that are resistant to these therapies at the time of their initial diagnosis. Even if the cancer is initially responsive to such therapies, it tends to become resistant to them over time. Such platinum-resistant ovarian cancers carry a grim prognosis. There is a very limited number of treatment options for these, and such patients live fewer than 12 months on average. All of this speaks to a great need for efficacious treatment options for these patients.

After showing promising results in a trial, Elahare is poised to address just this need. Given that there has been no new, efficacious drug for these patients since 2014, the FDA approval of Elahare is a momentous development.

“Patients will have a response rate of approximately 30% and on average this response will last about 7 months,” said Dr. Dana Chase, a gynecologic oncologist at Arizona Oncology. “This is an improvement on prior therapies available for this platinum-resistant group.”

Who Can Receive Elahare?

To be eligible to receive Elahare, a woman would have to be on platinum therapy that has failed or for whom it did not work, according to experts

“This an exciting new regimen for platinum resistant ovarian cancer patients whose tumors have the FOLR1 (or FRα) expression,” Dr. Bobbie Rimel, a gynecologic oncologist at Cedars-Sinai told SurvivorNet. “Targeted agents for ovarian cancer are a great opportunity for patients who otherwise would have only cytotoxic chemotherapy.”

FRα is a protein expressed on the surface of ovarian cancer cells. Almost 70% of ovarian cancers carry this protein at the time of diagnosis. If a patient has a recurrence, meaning that their cancer returned after initial treatment, this number increases to 80%. An overabundance of this protein on the cancer cell surface is usually an indication of aggressive disease that is likely to result in poor clinical outcomes for the patients.

Are Ovarian Cancers Regularly Tested For Folate Receptor α?

FRα protein levels are quantified using a special test called immunohistochemistry (IHC). As of now, IHC may not be routinely performed as part of ovarian cancer workup. However, ImmunoGen has partnered with the cancer laboratory testing company, NeoGenomics, to launch a free-of-cost FRα testing program, called FR-ASSIST.

Any patient with a diagnosis of ovarian cancer without prior FRα testing who resides and receives treatment within the USA is eligible to receive a free IHC for the protein through NeoGenomics. However, your oncologist may need to request this test for you by filling out a simple form.

As the importance of FRα testing becomes more clinically useful, this test may become a part of the routine workup for all ovarian cancer patients.

How Does Elahare Work?

Elahare is an antibody-drug conjugate. It consists of the antibody, mirvetuximab bound to the chemotherapy drug, soravtansine.

Mirvetuximab is an antibody against the FRα protein carried by ovarian cancer cells. An antibody is a protein molecule that binds to another unique protein molecule within the body. Thus, mirvetuximab specifically binds to the FRα protein, which causes the tumor cell to internalize the conjugate drug.

Once inside the tumor cell, soravtansine is released, which then targets tubulin and microtubules. These molecules and structures are responsible for maintaining the tumor cell structure and play an important role in its growth and propagation. Once they have been disrupted by soravtansine, the tumor cells can no longer survive.

What Does The Trial Show?

SORAYA evaluated the benefit and safety of Elahare in 106 patients with folate receptor alpha (FR α)-high, platinum-resistant ovarian cancer who have received one to three prior systemic therapies. At least one of these therapies should be Avastin. Avastin is an antibody that binds to a protein called the vascular endothelial growth factor (VEGF). VEGF promotes the development of blood vessels that feed and nourish the tumor. By binding to it, Avastin prevents new blood vessels from forming, thereby starving and eventually killing the tumor.

The patients in the trial received Elahare via IV infusions once every three weeks. Treatment continued until the drug stopped working or the patients could not tolerate it due to toxicity.

It is a phase III study, meaning that it offers the highest level of evidence in medicine. However, it must be noted that this drug was not compared to any other drug in the trial. Rather, the ability of this drug to cause a clinically meaningful response, termed objective response rate (ORR), in the patients was thoroughly evaluated using standardized criteria. The duration of this response (DOR) and progression-free survival (PFS) were also evaluated. PFS is the length of time a patient can live without a worsening of their disease.

ORR was observed in 31.7% of the patients. 4.8% of the patients had complete responses, which means that all of the observable tumors completely disappeared. A partial response was observed in 26.9% of these patients. Partial response signals a decrease in the amount of but not complete disappearance of disease on imaging scans. The average duration of this response was almost 6-7 months. These results may change with time, as some patients included in the trial continue to receive Elahare.

What Are The Risks?

Elahare is usually a well-tolerated drug. Nonetheless, it does have side effects that need to be managed. Across various clinical studies, the most common side effects are diarrhea, blurry vision, tiredness and fatigue, and nausea. Other less common side effects include an elevation of liver enzymes, which can indicate liver damage, damage to the cornea of the eyes, dry eyes, numbness, pain, or tingling in the hands and feet and decreased blood cell counts.

Drug side effects are graded on a scale of 1-5, with 1 being mild side effects that do not require any intervention and 5 indicating death. Elahare side effects were mostly grade 2 or lower, meaning that they were bothersome to the patients but could easily be managed with medications. However, sometimes these side effects did impact the quality of life of a patient to such a degree that they chose to discontinue treatment.

Sometimes, Elahare can cause serious, grade 3 or higher side effects. The impact on the eyes is the most often reported severe side effect. Up to 10% of the patients may experience grade 3 eye side effects, and around 0.2% may experience eye damage that requires hospitalization. Serious lung side effects have also been reported. Severe lung inflammation may occur in 0.3% of patients. Only 1 death has been attributed to lung toxicity from Elahare so far.

Can Patients Get Elahare Through Their Oncologist?

Given the FDA approval, if you meet the eligibility criteria for Elahare, you should be able to get it through your local oncologist.

“Elahere should be used when your ovarian, fallopian tube, or primary peritoneal cancer has recurred within 6 months of your last platinum-based chemotherapy and if your tumor has the biomarker folate receptor-alpha,” said Dr. Chase.

What Does The Future Hold For Elahare?

It is important to note that the SORAYA did not compare Elahare’s efficacy and safety to other drugs that are used to treat this cancer. To fully establish its clinical benefit and/or superiority, it needs to be tested against another treatment that is already in use. Such trials are currently enrolling patients and their results should be available in the coming years.