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Duke Physician Highlights Positive Ovarian Cancer Clinical Trial Results
Endometrial Cancer Consortium Expands to 25 Sites in the U.S.
Duke Physician Highlights Positive Ovarian Cancer Clinical Trial Results
By Shantell Kirkendoll, Senior Science Writer and Managing Editor, Duke University School of Medicine
Angeles Alvarez Secord, MD, MHSc, a gynecologic oncologist at Duke Health, shared encouraging new data on ovarian cancer treatment at the European Society for Medical Oncology (ESMO) meeting on Sept. 15, 2024, in Barcelona, Spain.
She was principal investigator of the PICCOLO trial, which tested mirvetuximab soravtansine (MIRV) for a particular form of cancer known as platinum-sensitive ovarian cancer (PSOC). The study focused on patients with high levels of a protein called folate receptor alpha (FRα).
The results were promising: over half of the patients in the phase II trial saw their cancer shrink or disappear, with an overall response rate of 51.9%. The treatment’s duration of response lasted an average of 8.25 months.
MIRV was approved by the U.S. Food and Drug Administration in 2023 for the treatment of platinum-resistant ovarian cancer (PROC). The drug is currently undergoing evaluation for approval in Europe, potentially expanding access to patients globally.
At previous national and international annual meetings for ESMO, the International Gynecologic Cancer Society (IGCS), the American Society of Clinical Oncology (ASCO) and the Society of Gynecologic Oncology (SGO) — for which Dr. Secord serves as immediate past president — the following background information was provided during the PICCOLO abstract presentation:
- There is no generally accepted standard of care with a clear efficacy benchmark based on prospective trials in third-line or later patients with platinum-sensitive ovarian cancer (PSOC)
- MIRV has encouraging activity as a monotherapy in platinum-resistant ovarian cancer (PROC) in patients whose tumors express high levels of FRα
Platinum-based chemotherapy can become less effective over time, and patients may experience severe side effects. MIRV offers a potentially more effective and less toxic treatment option.
—Angeles Alvarez Secord, MD, MHSc
Dr. Secord highlighted a major challenge faced by patients: those who take PARP inhibitors (PARPi), a type of maintenance treatment used after chemotherapy to keep cancer from coming back, tend to respond less to next-line treatments. This is especially true for treatment plans that use platinum-based drugs.
MIRV, however, has shown promise even in this difficult-to-treat population, providing a much-needed option for patients with few effective alternatives left.
Response rates were over 70% for those patients who have BRCA mutations or had not received a prior PARPi. For patients whose cancer worsened after taking PARP inhibitors, the treatment still showed positive results, with a 45.8% response rate. On average, the benefits lasted more than seven months.
The PICCOLO trial also tested how safe and effective MIRV is for patients and found that most patients handled the drug well. Common side effects included neurosensory issues, gastrointestinal problems, dry eye and blurred vision, but trial data indicated that these were mostly mild and resolved over time.
The unique composition of MIRV is considered key to its effectiveness. The drug is designed to target FRα, a protein commonly found on the surface of ovarian cancer cells. Once attached, a cleavable linker releases a potent cancer-killing agent, DM4, which interferes with the cancer cells’ ability to divide and spread.
This targeted approach allows MIRV to zero in on cancer cells while sparing healthy ones, offering a strategic advantage over traditional chemotherapies that can affect both.
About 20,000 women in the United States will have a new diagnosis of ovarian cancer this year, according to the American Cancer Society. Diagnoses have been slowly falling over the past few decades. Fewer women are dying of ovarian cancer as well, likely due to better treatments and fewer women being diagnosed.
Reference: duke.is/ACSKeyStatisticsOvarianCancer
MIRV is an antibody-drug conjugate (ADC) that combines an antibody that targets cancer cells with a potent anti-cancer drug. It is the first FDA-approved ADC for ovarian cancer and the only new therapy specifically for PROC.
Targeting Endometrial Cancer
At the June 6, 2024, SGO Virtual Congressional Briefing on Endometrial Cancer, Dr. Secord addressed endometrial cancer, the critical need for additional research and efforts for prevention and early diagnosis of women’s cancers.
The program also focused on the state of cancer care and the Department of Defense Ovarian Cancer Research Program. Noted was a decline in ovarian cancer cases and mortality. Of importance was the alarming rise in cases and deaths related to endometrial cancer.
In 2024, reporting shows for the first time, more women in the U.S. are dying of uterine cancer compared to ovarian cancers, specifically in younger populations.
Dr. Secord and colleagues addressed barriers to finding treatment and curing endometrial cancer, citing underfunding and lack of prioritization. Testing that does not cause significant discomfort for patients, newer treatments, why patients have relapse (even when promising regimens have been administered) and determining mechanisms for resistance need to be the focus. Access to care and the ability to participate in clinical trials are key and need to be addressed.
“There are only four FDA-approved drugs specifically for endometrial cancer since 1971. That is not acceptable,” Dr. Secord stated when specifying why progress has not been made to conquer this disease.
Since the congressional briefing, there have been several Food and Drug Administration-approved immunotherapy agents in combination with chemotherapy for patients with primary advanced or recurrent endometrial carcinoma.
Endometrial Cancer Consortium Expands to 25 Sites in the U.S.
With the initial support of the Kay Yow “Cancers that Affect Women” grant in 2019, Dr. Secord and Duke Cancer Institute established an Endometrial Cancer Consortium that now includes 25 sites across the country. The consortium has expanded research capabilities by harnessing information about endometrial cancer, the tumor makeup on a molecular level, what helps endometrial cancers grow and treatment outcomes. With this information, researchers hope to identify the right targeted therapy to use for treatment based on the tumor makeup and provide individualized care for patients.
The work of the consortium has resulted in six community awareness events, 15 abstract presentations, three nationally recognized awards and three subsequent research grants.