[Interview] 'Elahere brings meaningful survival gains in platinum-resista...

Ovarian cancer is one of the most challenging gynecologic malignancies to diagnose early and treat effectively, largely due to its vague symptoms and high recurrence rate.

Many patients are diagnosed at an advanced stage and experience repeated relapses despite surgery, chemotherapy, and maintenance therapy, gradually developing resistance to treatment. Once the disease becomes platinum-resistant -- defined as recurrence within six months after the last platinum-based chemotherapy -- treatment options become severely limited.

Against this backdrop, Elahere (mirvetuximab soravtansine) has emerged as the first folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) approved for ovarian cancer.

In the pivotal MIRASOL trial, Elahere demonstrated improvements across all key efficacy endpoints -- including objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS) -- compared with non-platinum chemotherapy. Most notably, it showed a statistically significant OS benefit in platinum-resistant ovarian cancer, a result rarely seen in this treatment setting.

“Most patients with platinum-resistant ovarian cancer are symptomatic and require urgent treatment, but conventional therapies rarely achieve response rates above 20 percent,” said Professor Lee Yoo-young of the Department of Obstetrics and Gynecology at Samsung Medical Center. “In the MIRASOL study, Elahere increased the response rate to over 40% and consistently improved both PFS and OS.”

Korea Biomedical Review spoke with Professor Lee about the current challenges in ovarian cancer treatment and the clinical significance of Elahere.

Professor Lee Yoo-young of Samsung Medical Center discussed the clinical value of Elahere for patients with platinum-resistant ovarian cancer during a recent interview with Korea Biomedical Review. (Courtesy of AbbVie Korea)

Question: Ovarian cancer is known for its poor survival outcomes due to the difficulty of diagnosis and treatment. Why is ovarian cancer so difficult to diagnose and treat?

Answer:

The biggest challenge is that ovarian cancer rarely causes clear symptoms in its early stages. In most cases, patients visit a hospital either because they develop symptoms or because abnormalities are found during routine health screenings. Diseases that can be detected early are usually identified within standard screening systems, but ovarian cancer is often asymptomatic. Even when symptoms are present, they tend to be nonspecific—such as indigestion or abdominal discomfort—which makes it difficult to suspect ovarian cancer.

Multiple clinical studies have consistently shown that ovarian cancer is difficult to detect early. Because symptoms are vague and routine tests are not sufficient for early diagnosis, about 70 percent of patients are diagnosed with advanced disease. When cancer is first discovered at an advanced stage, tumor burden is already substantial, and the risk of recurrence remains high even after treatment. That is why ovarian cancer continues to be considered a difficult-to-treat malignancy.

Q: Ovarian cancer is also known for frequent recurrence. How has recurrent ovarian cancer traditionally been treated?

A:

The goal of first-line treatment is essentially a cure. The current standard of care consists of three pillars: surgery, chemotherapy, and maintenance therapy. Outcomes have improved compared with the past, but recurrence rates remain high.

Once recurrence occurs, cure becomes difficult except in a small subset of patients, and treatment goals shift accordingly. The focus becomes aggressive disease control and symptom management to help patients maintain daily functioning and quality of life.

After recurrence, additional chemotherapy is administered as needed. However, because patients have already undergone first-line chemotherapy, recurrent tumor cells have often acquired some degree of drug resistance. Even with palliative treatment, disease progression may continue, and repeated relapses further accumulate resistance. Eventually, many patients progress to a stage where the disease no longer responds well to chemotherapy.

Platinum-resistant ovarian cancer is defined as recurrence within six months after the last platinum-based chemotherapy. At that point, treatment becomes particularly difficult, and patients’ quality of life is significantly affected.

Q: What are the characteristics and unmet needs of platinum-resistant ovarian cancer?

A:

Platinum-sensitive and platinum-resistant ovarian cancer are clinically very different. Patients whose disease recurs more than six months after platinum therapy often remain asymptomatic despite recurrence. In such cases, tumor burden may be relatively low, and clinicians can sometimes consider observation rather than initiating chemotherapy immediately.

There was even a phase 3 trial comparing early chemotherapy versus delayed treatment in asymptomatic recurrent patients with relatively small tumor burdens. The study found no significant difference in final oncologic outcomes. In fact, patients who started chemotherapy earlier experienced poorer quality of life initially because chemotherapy itself imposes a substantial burden.

However, the situation changes completely once the disease becomes platinum-resistant. By then, patients usually have accumulated tumor burden from multiple relapses and treatments, and most are symptomatic. Treatment becomes urgent, yet existing therapies have historically produced limited responses, with symptoms often improving only minimally.

In this setting, ORR becomes an especially important endpoint. It reflects the proportion of patients achieving complete or partial tumor shrinkage. In platinum-resistant ovarian cancer, even stable disease can be clinically meaningful because the disease would otherwise continue progressing. Maintaining disease stability alone may represent a therapeutic benefit.

Still, if we focus strictly on actual tumor shrinkage, conventional therapies rarely exceeded response rates of 20 percent. In practical terms, only about two out of ten patients experienced meaningful tumor reduction, while most saw disease progression. As tumor burden increases, patients’ overall condition deteriorates. Since chemotherapy requires patients to maintain sufficient physical status, poor responses and declining health create a vicious cycle that can ultimately lead to death.

When discussing prognosis with patients and caregivers, I explain that while platinum-resistant ovarian cancer does not necessarily lead to immediate critical decline or death within one or two months, it has historically been difficult to expect long-term survival beyond one year.

Professor Lee Yoo-young (Courtesy of AbbVie Korea)

Q: Elahere has now been approved in Korea. What is its clinical significance?

A:

Elahere delivered results that were difficult to achieve with previous therapies for platinum-resistant ovarian cancer. The most striking finding is the response rate. Conventional therapies produced ORRs of roughly 19–20 percent, whereas the MIRASOL trial showed an ORR of 42.3 percent with Elahere—more than double.

That level of response translates into substantial tumor reduction in real patients, thereby significantly improving quality of life. One common symptom in platinum-resistant ovarian cancer is bowel obstruction caused by intra-abdominal tumors. Patients struggle with eating, bowel function, and gas passage. As tumors shrink, these symptoms may also improve.

Clinical trials evaluate treatment efficacy through several endpoints. ORR measures the proportion of patients who respond, while DoR reflects the duration of the response. If a response disappears within one or two months, the clinical benefit is limited. Durable responses can translate into improvements in PFS and eventually OS.

What stood out in MIRASOL was the consistent improvement across ORR, DoR, PFS, and OS. Elahere monotherapy improved median PFS to 5.62 months compared with 3.98 months for non-platinum chemotherapy, reducing the risk of progression or death by 35 percent. Median OS improved to 16.46 months from 12.75 months, corresponding to a 33% reduction in mortality risk. ORR reached 42.3 percent, compared with 15.9 percent in the control arm.

One patient from the MIRASOL study remains particularly memorable to me. After failing prior therapies and progressing to platinum-resistant disease, the patient tested positive for FRα and enrolled in the trial.

Following Elahere treatment, the patient’s lesions nearly disappeared, and the response lasted for approximately 14 months. Although the disease eventually recurred, such a prolonged response would have been difficult to imagine in the past for platinum-resistant ovarian cancer. Symptoms improved rapidly, allowing the patient to return to daily life, and adverse events remained manageable. The final study results, later published, were very much in line with what we had observed clinically.

Q: Elahere is the first FRα-targeted therapy in ovarian cancer. How is the FRα biomarker used in real-world practice?

A:

Elahere is the first ADC targeting FRα in ovarian cancer. In my view, this is the first truly breakthrough therapy to emerge in platinum-resistant ovarian cancer in about a decade.

Unlike conventional cytotoxic chemotherapy, ADCs are designed to deliver anticancer agents directly to tumor cells by attaching them to antibodies targeting specific antigens. In theory, this allows more selective drug delivery to cancer cells while sparing normal tissues. That is why biomarker expression and expression level are critically important. Higher expression generally means greater antibody binding and potentially stronger efficacy.

For Elahere, eligibility requires at least 75 percent of tumor cells to show membrane staining intensity of 2+ or higher. This highlights the importance of companion diagnostics (CDx), which are diagnostic tests approved for use with specific therapies to identify patients most likely to benefit.

Broadly speaking, FRα-positive ovarian cancer could include tumors with staining intensities of 1+, 2+, or 3+, making the target population seem quite large. However, under Elahere’s companion diagnostic criteria, FRα positivity specifically refers to tumors in which at least 75 percent of cells demonstrate membrane staining intensity of 2+ or higher.

These criteria could evolve in the future if newer drugs prove effective in patients with lower FRα expression. But at present, clinically meaningful responses to Elahere have been demonstrated in patients meeting the current threshold, which is why the approved indication is limited to that population.

Q: Is FRα testing difficult to implement in clinical practice?

A:

FRα testing is relatively straightforward. For a companion diagnostic to have clinical value, it is important to use the same methodology applied in the clinical trials. Fortunately, FRα assessment is based on protein expression rather than complex genetic analysis. Testing is neither excessively expensive nor time-consuming.

FRα also has advantages as a biomarker because its expression tends to remain relatively stable throughout the disease course. Tumors evolve over time, and some biomarkers change as the disease recurs and progresses. However, FRα expression is believed to remain fairly consistent from initial diagnosis through recurrence.

In theory, a stable biomarker means the initial test result may remain relevant throughout the patient’s treatment journey. FRα-positive tumors are estimated to account for about 30–40 percent of ovarian cancer cases.

Q: Few therapies in ovarian cancer have demonstrated an OS benefit. What is the significance of the MIRASOL findings?

A:

To demonstrate an OS benefit, two conditions generally need to be met. First, the therapy must provide a sufficiently large survival benefit early on. Although survival advantages may diminish over time, a later survival difference suggests that the initial benefit was substantial. Elahere demonstrated this in platinum-resistant ovarian cancer.

Second, the therapy should not negatively affect subsequent treatments. Since ADCs still carry cytotoxic payloads, there is concern that they could induce resistance that compromises later therapies, potentially eliminating any OS advantage.

However, Elahere did not appear to adversely affect the efficacy of subsequent treatments. I believe these two factors together contributed to the OS improvement observed in MIRASOL.

If a therapy negatively impacts future treatment responses, sequencing decisions become much more complicated. So far, Elahere does not appear to raise major concerns in that regard.

Q: The Korean Society of Gynecologic Oncology has also incorporated Elahere into its recommendations. How is its clinical value viewed in current guidelines?

A:

The MIRASOL study supporting Elahere received the highest level of evidence and recommendation grade. That reflects how strongly the academic community values the trial data. In a disease like platinum-resistant ovarian cancer—where alternative options are limited, and treatment urgency is high—demonstrating an OS benefit carries substantial clinical significance.

Q: Since Elahere is an ADC, there are expectations that treatment burden may be lower than with conventional chemotherapy. What has your experience been like?

A:

The patient I mentioned earlier had significant difficulty eating after progressing to platinum-resistant disease. Once patients cannot eat properly, the quality of life declines rapidly. Gas-related pain develops, and daily life becomes extremely difficult.

After starting Elahere, those symptoms improved remarkably quickly. One of the advantages I observed personally was the relatively rapid onset of treatment response. The patient was able to maintain normal daily activities for nearly a year.

Of course, there were concerns regarding adverse events. Ocular toxicities occurred, but they were low-grade and consistent with prior reports in the literature. The patient temporarily used corrective glasses and discontinued them once symptoms improved. We monitored the patient regularly through ophthalmologic examinations, but no adverse events significantly affecting quality of life were observed.

Q: Ocular adverse events may concern patients. Are they manageable with multidisciplinary care?

A:

Whenever a new therapy is introduced, we monitor patients very carefully because unexpected situations can arise. At the time, we had strong collaboration with ophthalmology at a tertiary referral hospital, and the ocular events we encountered were not severe.

With proper communication and education among patients and healthcare providers, I believe these events can be adequately managed even outside major academic centers through coordinated regional care networks.

Adverse events are objective findings, but their interpretation and management also depend on clinical experience. As clinicians gain familiarity with ADCs, there is growing recognition that these toxicities are manageable.

Because ADCs contain cytotoxic payloads, treatment-related adverse events can still occur. However, the mechanism is designed to deliver chemotherapy more selectively to cancer cells, so overall toxicity is expected to be lower than with traditional cytotoxic agents.

In Elahere trials, hematologic toxicities were relatively limited, which is a major clinical advantage. Lower hair loss rates are also meaningful to patients.

Q: What is the biggest obstacle preventing patients from accessing Elahere?

A:

Access to treatment remains the biggest challenge. I have raised this issue during discussions at the National Assembly as well. If a therapy has strong scientific evidence, has already been approved, and is available in clinical practice, yet patients still cannot access it, leading them to lose six months, one year, or even more potential survival benefit, that is ethically problematic.

Platinum-resistant ovarian cancer has few alternative options and requires urgent treatment. Rapid reimbursement coverage for Elahere is therefore essential. Pharmaceutical companies are making efforts through patient support programs, but the financial burden remains substantial for many patients. For approved therapies to truly reach patients in real-world practice, reimbursement is critical.

Q: Lastly, what message would you like to share with ovarian cancer patients?

A:

The incidence of ovarian cancer continues to rise, but at the same time, tremendous efforts are being devoted to treatment and research. Many promising therapies are under development. Data from both Korea and abroad show that patients diagnosed more recently tend to have better survival outcomes than those diagnosed earlier, largely because new therapies and treatment strategies continue to emerge.

The same is true in ovarian cancer. Elahere has now been introduced, and many clinical trials of novel therapies are actively underway. There is reason to remain hopeful about future progress. I hope patients and caregivers do not lose hope.

Hong Sook