Elahere Shows Promise in New Trial
- Ovarian cancer is difficult to treat and often comes back even after successful treatment. When it does, it tends to be more aggressive and resistant to traditional platinum-based chemotherapies.
- Ovarian cancer cells commonly carry folate receptor alpha (FRÎ±) protein on their surface. Up to 80% of new and recurrent ovarian cancers may carry this protein. Generally, FRÎ± levels tend to be high in more aggressive ovarian cancers.
- Oncologists can order FRÎ± testing for their ovarian cancer patients through NeoGenomics at no cost; FRÎ± can be targeted by the new drug, Elahere. It is a unique drug, which is part antibody, part chemotherapy. Due to promising new data, the drug is expected to get regular approval in the U.S.
- In a phase III trial, more than one-third of patients receiving Elahere (who had previously been treated with a drug called bevacizumab) experienced improved progression-free survival (time without symptoms worsening) and one-fourth experienced improved overall survival.
- Common side effects associated with Elahere 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 Elahere so far.
Elahere was given accelerated approval by the FDA earlier this year. It targets the folate receptor alpha (FRÎ±) protein present on the tumor cell surface. The accelerated approval was based on a rigorous clinical trial called SORAYA, which showed effectiveness at suppressing cancer growth in at least one-third of patients.Read More
‘Practice-changing’ Results“Now we’ve shown that Elahere is better than the available therapies. … We have longer progression-free survival, which means the patients are living longer without their cancer progressing. And most importantly, we have demonstrated that patients are living longer,” Anna Berkenblit, Chief Medical Officer at biotech company Immunogen, which sponsored the MIRASOL trial, told SurvivorNet. “…This is unprecedented and it is practice changing.” The findings indicate that patients with ovarian cancer should speak to their doctors about testing for the FRÎ± protein and see if they are eligible for this ground-breaking new treatment.
Dr. Ursula A. Matulonis, chief of the Division of Gynecologic Oncology at Dana-Farber and Co-Principal Investigator of the SORAYA study, expressed excitement at Elahere’s potential after the accelerated approval.
“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,” she said. “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.”
What Is Ovarian Cancer?
Ovarian cancer is one of the deadliest cancers. Of all the women who will be diagnosed with ovarian cancer, only 47% will be alive 5 years after their diagnosis. In the US, around 20,000 women will be diagnosed with ovarian cancer in 2022, and it will result in around 13,000 deaths.
The reasons for these poor outcomes are many. Firstly, there is no screening test for ovarian cancer.
Secondly, and perhaps more importantly, the early stages of this cancer may produce no symptoms or only vague symptoms that are often misdiagnosed. These symptoms can include pain in the abdomen, nausea, bloating, feeling full after eating small amounts of food, tiredness, and a change in bowel habits, among other things.
These symptoms can also occur in many other conditions, most of which are benign. Thus, it is not uncommon for these cancers to go undiagnosed well into the later stages, such as stage 3 or 4.
Unfortunately, the later the stage, the more challenging its treatment. Even if the cancer is caught and treated at early stages, the chance of it returning in the future at almost 80%.
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 trials, Elahere 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 Elahere 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 Elahere?
To be eligible to receive Elahere, 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 FRÎ±) 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.”
FRÎ± 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 Î±?
FRÎ± 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 FRÎ± testing program, called FR-ASSIST.
Any patient with a diagnosis of ovarian cancer without prior FRÎ± 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 FRÎ± testing becomes more clinically useful, this test may become a part of the routine workup for all ovarian cancer patients.
How Does Elahere Work?
Elahere is an antibody-drug conjugate. It consists of the antibody, mirvetuximab bound to the chemotherapy drug, soravtansine.
Mirvetuximab is an antibody against the FRÎ± 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 FRÎ± 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 Do The Trials Show?
SORAYA evaluated the benefit and safety of Elahere in 106 patients with folate receptor alpha (FR Î±)-high, platinum-resistant ovarian cancer who have received one to three prior systemic therapies. It was 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.
The results of the SORAYA trial were promising enough that the drug was given emergency approval by the FDA and the MIRASOL trial added to that, making a full FDA approval likely.
The MIRASOL trial, meant to further evaluate the safety and efficacy of the drug, looked at how it performed compared to giving chemotherapy alone in patients with folate receptor alpha (FRÎ±)-positive platinum-resistant ovarian cancer.
In the trial, more than one-third of patients (36%) receiving Elahere (who had previously been treated with a drug called bevacizumab) experienced improved progression-free survival and more than one-fourth (26%) experienced improved overall survival.
In another, smaller group of patients who had not previously been treated with bevacizumab, progressional free survival was 34% better and overall survival was 49% better than when patients received standard chemotherapy.
There is also some hope that the new drug can be used when ovarian cancer is diagnosed in earlier stages.
“It's also worth noting that ongoing studies are evaluating moving the drug to being used in earlier stages of the disease,” said Dr. Kathleen Moore, Associate Director of Clinical Research at the Stephenson Cancer Center at the University of Oklahoma, who presented the MIRASOL findings.
What Are The Risks?
Elahere 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. Elahere 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, Elahere 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 Elahere so far.
Can Patients Get Elahere Through Their Oncologist?
Given the FDA approval, if you meet the eligibility criteria for Elahere, 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.
Questions to Ask Your Doctor
- Has my cancer been tested for the FRÎ± protein?
- Can/should you order an immunohistochemistry (IHC) test?
- Am I eligible for Elahere?
- What side effects should I be aware of?
- What additional tests might I need?