‘Elahere demonstrates OS benefit in ovarian cancer’

Recurring ovarian cancer… Introduction of Elahere signals a shift in FRα-targeted treatment strategies

Clinically significant OS improvement shown in trials… importance of biomarker testing highlighted

The treatment landscape for platinum-resistant ovarian cancer (PROC), which is characterized by high relapse rates and limited effectiveness of standard therapies, is showing signs of change.

Elahere (mirvetuximab soravtansine), the first folate receptor alpha (FRα)-targeted antibody–drug conjugate (ADC) approved for ovarian cancer, has demonstrated improved overall survival (OS) in a global Phase III clinical trial and obtained regulatory approval in Korea.

Kidong Kim, Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital

Professor Kidong Kim from the Department of Obstetrics and Gynecology at Seoul National University Bundang Hospital said, “Ovarian cancer relapses frequently, and once it progresses to platinum resistance, median survival is often less than one year. With the advent of Elahere, identifying FRα expression earlier during diagnosis is becoming increasingly important in establishing individualized treatment strategies.”

Ovarian cancer is a gynecological cancer originating in the ovaries, fallopian tubes, or primary peritoneum. Approximately 3,000 to 3,500 new cases are diagnosed annually in Korea. Due to accumulated risk factors such as reduced childbirth rates, early menarche, and late menopause, the number of patients is on the rise. Notably, as more than two-thirds of patients are in their 40s to 60s, the age group most active in family and social life , diagnosis is particularly impactful on patients, families, as well as society as a whole.

Upon diagnosis, standard first-line treatment consists of surgery followed by platinum-based chemotherapy. While many patients respond to first-line therapy, approximately 80% eventually experience recurrence.

With each recurrence, the tumor acquires resistance to platinum-based anticancer drugs, eventually progressing to the stage of platinum-resistant ovarian cancer, where this treatment becomes largely ineffective. Patients who relapse within six months of initial treatment are classified as having typical platinum-resistant ovarian cancer. By this stage, the patient's overall health is often significantly compromised, and available subsequent treatment options are extremely limited.

Elahere, which was approved in Korea in December last year, is the first novel mechanism therapy introduced for ovarian cancer in nearly a decade. Elahere is an FRα-targeted ADC expressed on the surface of cancer cells, enabling a form of precision therapy distinct from conventional cytotoxic chemotherapy.

FRα is minimally expressed in normal tissues but is highly overexpressed in ovarian cancer cells. Studies indicate that approximately 35–40% of ovarian cancer patients are FRα-positive and meet Elahere’s treatment criteria. More importantly, FRα expression tends to remain relatively consistent from diagnosis through recurrence, making it a useful biomarker throughout the disease course.

Elahere consists of an FRα-targeting antibody linked to a cytotoxic payload. Upon administration, the antibody selectively binds to FRα on tumor cells, is internalized, and releases the payload to induce cancer cell death while exerting a bystander effect on neighboring tumor cells. This mechanism enables a precision anticancer strategy that minimizes damage to normal tissue with potent antitumor activity.

Professor Kim explained, “While there have been various attempts to develop new drugs in the field of platinum-resistant ovarian cancer in the past, few have achieved clinically significant success. With the broader adoption of the ADC platform, some drugs have begun to show meaningful results, and Elahere is one drug that represents this trend.”

Q. How were platinum-resistant ovarian cancer patients who do not respond to platinum-based therapy treated in the past?

First-line treatment typically involves platinum-based chemotherapy. Upon relapse, platinum-based chemotherapy may be reused depending on the relapse interval, but for patients who relapse shortly after platinum-based therapy, other drugs are used, excluding platinum-based agents. Recurrence within 6 months after platinum-based therapy is termed platinum-resistant ovarian cancer, which has limited treatment response and a very poor prognosis, with survival typically under 1 year.

Currently approved options include pegylated liposomal doxorubicin and topotecan (as non-platinum-based regimens for platinum-resistant ovarian cancer). The overall efficacy of these agents is similar, and there have been challenges in practice due to their limited efficacy and response rates.

While study results vary, some report objective response rates as low as 5%. This means only about 5 out of 100 patients show tumor size reduction. Failure of such treatment typically leads to a cycle of switching to different anticancer drugs and continuing treatment with diminishing benefit.

Q. Could you explain the MIRASOL trial that supported Elahere’s approval? What were the characteristics of the patients enrolled, and what were the study results?

MIRASOL was a randomized clinical trial in platinum-resistant ovarian cancer patients. The experimental arm received Elahere monotherapy, while the control arm received standard non-platinum chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). Approximately half of the participants had received three or more prior lines of therapy, and some had prior exposure to bevacizumab or PARP inhibitors.

The study results confirmed a statistically significant improvement in progression-free survival (PFS) in the Elahere treatment group compared to the control group. However, Elahere garnered even more attention because it demonstrated a difference in overall survival (OS). While drugs showing PFS improvement had existed before, a drug proving a statistically significant improvement in overall survival had been absent for a long time. In this context, Elahere became the first drug to demonstrate an OS improvement of approximately 4 months (mOS 16.46 vs 12.75), and these results were why Elahere received such significant attention.

Q. Confirming FRα expression status is essential for Elahere treatment. When is the most appropriate time to perform the companion diagnostic testing to determine FRα positivity?

Ideally, FRα expression should be assessed at initial diagnosis using tumor tissue obtained during surgery. There are two reasons for this.

First, some studies indicate that FRα expression tends to remain relatively consistent both at initial diagnosis and at recurrence. While some biomarkers may show changing expression levels as the disease progresses, FRα has demonstrated consistent expression in research. This allows the results from the initial diagnostic test to be utilized for subsequent treatment decisions.

Another reason lies in the nature of ovarian cancer. Ovarian cancer frequently recurs, and during recurrence, multiple drugs are selected and used sequentially. In this process, prior treatment choices often influence the treatment options available at recurrence. Determining FRα expression at the initial diagnosis stage helps establish the best overall treatment strategy for the patient.

Selecting the most effective drug early on can lead to more favorable outcomes for the patient, especially in the current environment where various treatment options exist. Conversely, if FRα expression is confirmed and Elahere is used only after all other options have been exhausted, there is a possibility that a better choice could have been made at an earlier stage. For these reasons, we believe it is advantageous to perform the FRα companion diagnostic test as early as possible in the diagnostic process.

Q. The MIRASOL study demonstrated PFS improvement with Elahere. However, based solely on absolute numbers, the PFS benefit may appear modest numerically. What is its clinical significance?

When discussing treatment options with patients, the question inevitably arises: ‘How much tangible benefit would this drug actually provide?’ Two key points warrant consideration here.

First, platinum-resistant ovarian cancer is a disease that is extremely difficult to treat. Despite the development of numerous drugs over the years, none have demonstrated sufficient clinical benefit. Therefore, the fact that a statistically significant improvement was observed, regardless of the absolute median difference, is meaningful.

Moreover, while median values reflect population averages, individual patient responses may vary greatly. In MIRASOL, Elahere achieved an objective response rate of 42.3%. For example, consider a patient with two or three tumor lesions. After Elahier treatment, two lesions completely disappeared, leaving only one. In such a responding patient, the possibility of attempting a cure through additional radiotherapy or surgery, while rare, clearly exists.

In other words, the finding that progression-free survival was extended by an average of about 2 months is merely the result of a group comparison. The actual benefit for individual patients could be significantly greater.

Q. How do you assess Elahere’s safety profile?

ADC therapies function by binding cytotoxic anticancer agents to antibodies for delivery to tumor cells, so they can be considered to have characteristics similar to traditional cytotoxic anticancer agents (chemotherapy). Therefore, while the degree and presentation may differ, adverse events seen with traditional cytotoxic anticancer agents can occur, and a similar approach to adverse event management would be necessary.

Ocular adverse events are notable, and because clinical experience is still accumulating, it is important to recognize that healthcare providers are still in the process of gaining sufficient clinical experience with ocular adverse events caused by this drug. Therefore, I believe clear management guidelines and clinical consensus regarding ocular adverse events for ADC-based therapies will be established as real-world use expands.

Q. I understand you have experience prescribing Elahere. Could you share your treatment experience?

I have experience treating patients with Elahere through the Expanded Access Program (EAP) and clinical trials. A patient currently receiving treatment through EAP has completed approximately 5 cycles of the drug. The patient is still responding to treatment and continuing therapy without any particular adverse events.

Another patient who participated in a clinical trial experienced a reduction in tumor size but also encountered ocular adverse events. While more data is being accumulated, appropriate management strategies and sufficient clinical data still need to be further established.

Q. Do you have any recommendations on improving the ovarian cancer treatment environment?

Ultimately, the hope of all patients and medical professionals is for the development of a treatment that can achieve a cure even in platinum-resistant ovarian cancer. While rare cases of near-complete remission have been observed with existing treatment options, the mechanisms underlying such high treatment responses remain unclear. Active research and development of various novel drugs are underway to understand these mechanisms and identify more effective treatment strategies.

Alongside this, I believe that managing adverse events is just as critical as treatment efficacy in the real-world setting. It is not uncommon for patients to have poor treatment adherence due to difficulty making outpatient visits because of their circumstances. In such situations, the occurrence of adverse events can lead to rapid treatment discontinuation. Therefore, I believe that the better the drug, the more crucial adverse event management becomes in actual clinical practice.

Treatment accessibility is also a crucial factor. Elahere is the first treatment to demonstrate a statistically significant improvement in overall survival (OS) in platinum-resistant ovarian cancer. If practical access improves in the future, we expect more patients will have the opportunity to receive this treatment.