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Study could help recommend the best treatment for women with early-stage mucinous ovarian cancer

This is an edited version of an article reviewed by Emilie Henderson, B.Sc., and published on News-Medical.Net  Oct. 12, 2022

A global study into mucinous ovarian cancer could help oncologists recommend the best treatment for women who are diagnosed early with the condition.

By looking down a microscope for two different 'patterns of invasion' – the way that cancer cells invade ovarian tissue – oncologists can better predict which patients may have better or worse prognoses and can target treatment accordingly. The finding was reported in a paper published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"Mucinous ovarian cancer is a rare type of ovarian cancer. It actually has more in common with gastrointestinal cancers, and can be hard to diagnose and hard to treat once it has spread beyond the ovaries," says lead author Nicki Meagher, who has just completed her PhD in the Molecular Oncology group, University of New South Wales School of Clinical Medicine.

She says that observing which of the two types of invasion patterns that the cancer cells form could help specialists decide on treatment strategies.

The two patterns of invasion are defined by the way the cancer cells organize themselves when viewed under a microscope. The infiltrative pattern of invasion associated with poorer health outcomes shows cancer cells spreading in an uneven, haphazard way through the ovarian tissue. The other pattern is known as expansile, where cells expand through tissue in a more orderly manner, and is associated with better prognoses.

Up until now, other studies had suggested that the infiltrative pattern of invasion was associated with poorer patient outcomes, but no study had large enough numbers of patients with early-stage cancer to reach statistical significance.

But the current study, that involved more than 100 researchers in Australia, UK, Canada, Asia, Europe and the US, was able to test this hypothesis in much larger numbers by examining the tissue of 604 patients. The researchers also looked for the expression of 19 genes including THBS2 and TAGLN in addition to the patterns of invasion.

Professor Susan Ramus who oversaw the global study and heads the Ovarian Tumour Tissue Analysis consortium says that guidelines on how to treat women with early-stage mucinous ovarian cancer have differed around the world due to limited data on infiltrative patterns of invasion associated with survival rates.

"For example, in some parts of the world, an infiltrative pattern was acknowledged as an important feature and determined what treatment those women receive," Professor Ramus says.

"Whereas in others, all patients are recommended for the same pathway of treatment. We hope that after this large study treatment guidelines can be aligned and that we can target treatment for women who may have these more serious indicators, even if they are diagnosed in early stages."

The researchers also noted that women with higher expression of two genes, THBS2 and TAGLN in their tumors, had poorer overall survival.

"We're hoping that this may be able to help explain some of the biology potentially down the track," says Ms Meagher.

"Another avenue could be that knowledge of expression of these genes could assist in developing targeted drugs."

The researchers are part of a wide network of experts who plan to carry out a validation study to further investigate these genomic markers as the basis for a targeted treatment strategy.

Two New Studies Help Improve the Understanding of Ovarian Cancer

 This is an edited version of an article reviewed Emilie Henderson, B.Sc., and published on News-Medical.Net  Oct. 11, 2022

Two new discoveries led by Cedars-Sinai Cancer investigators help improve the understanding of what drives the development of ovarian cancer and why some women's tumors do not respond to therapy. 

Scientists identify mutations tied to increase risk of ovarian cancer

The first study, published today in the Journal of the National Cancer Institute, identified four new regions of the human genome that harbor genetic variants or mutations that put women at an increased risk of developing epithelial ovarian cancer, the most common type of ovarian cancer.

"When it comes to ovarian cancer, prevention is how we're really going to impact mortality," said Michelle Jones, PhD, a research scientist in the Center for Bioinformatics and Functional Genomics and corresponding author of the study. "This study helps us accurately identify women who carry cancer-causing mutations, which can help physicians develop preventive strategies for these women."

To pinpoint the mutations, the team of investigators used new methods to analyze the structural variation of the genome, which is made up of 23 pairs of chromosomes where an individual's genetic code is stored.

While most research focuses on analyzing the change in the sequence of the gene, the team looked at the number of copies of the gene an individual has-;known as a copy number variant.

When the genome gets copied, structural variation can occur, and stretches of the genome can get deleted, duplicated or rearranged to another position. These changes can lead to diseases, like cancer.

The researchers collaborated with scientists at the University of Cambridge to specifically look at deletions and duplications in 13,000 women with ovarian cancer and compared them to 17,000 women without ovarian cancer from the Ovarian Cancer Association Consortium to identify copy number variants that were associated with ovarian cancer risk.

They found significant deletions and duplications in the BRCA1 gene, BRCA2 gene, and RAD51C gene, all of which are known to harbor changes in a patient's DNA sequence that increase risk for ovarian cancer. Also found: four new genes that have not been previously linked to an increased risk for ovarian cancer.

The study, which is the largest to date to evaluate the contribution of copy number variants to ovarian cancer risk, will likely lead to more accurate genetic testing for women.

"We have the technology that can pick up these deletions and duplications, but it's not always done consistently in clinical genetic testing," said Jones. "We hope these findings highlight the value of looking at copy number variants in clinical genetic testing."

Gene expression unlikely to drive chemotherapy resistance in ovarian cancer

The second study, published in the Journal of Experimental & Clinical Cancer Research, gives investigators a deeper understanding as to how ovarian tumors develop resistance to chemotherapy, which occurs in about 80% of high-grade serous ovarian cancer patients and ultimately leads to their succumbing to the disease.

Previously, researchers believed that ovarian tumors evolve after they are exposed to chemotherapy, and that they change their gene expression to adapt and survive through the treatment.

However, using whole genome sequencing, they found for the first time that this is not the case. Instead, it seems more likely that most high-grade serous ovarian tumors have the capacity to survive chemotherapy from a very early stage, said Jones, who is also the co-first author on this study.

"This study has changed our understanding of how tumors respond to chemotherapy," Jones said. "Previously it was thought that we could probably find a way to treat chemo-resistant tumors with other drugs after they have been treated with the standard therapy, but this study suggests that may not be the best approach."

"By improving our understanding as to how tumors ... survive chemotherapy, and even continue growing throughout treatment, as well as finding vulnerabilities in the tumors, will give us an opportunity to design better drugs and save the lives of women with ovarian cancer," added Gayther....

Olaparib Plus Bevacizumab Maintenance Therapy Provides OS Benefit in Advanced HRD-Positive Ovarian Cancer

  This is an edited version of an article written by Kristie L. Kahl and published in OncLive Sept. 9, 2022

Maintenance olaparib (Lynparza) plus bevacizumab (Avastin) following first-line standard-of-care treatment improved overall survival (OS) in patients with newly diagnosed advanced ovarian cancer, particularly those with homologous recombination deficiency (HRD), according to final OS results from the phase 3 PAOLA-1/ENGOT-ov25 ... trial presented at the 2022 ESMO Congress.

“These data confirm the addition of olaparib to bevacizumab as a standard of care for HRD-positive patients in this setting and the importance of precision medicine and biomarker testing to guide treatment decisions,” Isabelle L. Ray-Coquard, MD, PhD, a medical oncologist at Centre Léon Berard Université Claude Bernard in Lyon, France, said during a presentation of the data....

Rucaparib Maintenance Elicits PFS Benefit in Newly Diagnosed Ovarian Cancer

 This is an edited version of an article written by Hayley Virgil and published in OncLive Sept. 11, 2022

Rucaparib (Rubraca) maintenance therapy improved progression-free survival (PFS) vs placebo in patients with newly diagnosed ovarian cancer, according to disease risk subgroup analyses from the phase 3 ATHENA–MONO study....

The goal of the ATHENA-MONO trial was for investigators to assess the PFS of rucaparib and placebo across subgroups of patients with newly diagnosed ovarian cancer, including surgical outcomes by surgeon’s assessment and by the response to first-line chemotherapy by radiographic scans....

Rucaparib (Rubraca) maintenance therapy improved progression-free survival (PFS) vs placebo in patients with newly diagnosed ovarian cancer, according to disease risk subgroup analyses from the phase 3 ATHENA–MONO study (NCT03522246).

Niraparib Maintenance Provides Durable Long-term Remission in High-Risk Advanced Ovarian Cancer

 This is an edited version of an article written by Kristi Rosa and published in OncLive Sept. 15, 2022

Maintenance treatment with niraparib (Zejula) produced a sustained and durable progression-free survival (PFS) benefit in patients with primary advanced ovarian cancer who responded to first-line platinum-based chemotherapy, spanning biomarker subgroups, according to updated data from the phase 3 PRIMA trial....

Data presented during the 2022 ESMO Congress showed that at a median follow-up of 3.5 years, which had a data cutoff date of November 17, 2021, the median progression-free survival (PFS) with niraparib was 24.5 months per investigator assessment vs 11.2 months with placebo in the homologous recombination deficiency (HRD) population....

In the overall population (n = 733), the median investigator-assessed PFS with niraparib was 13.8 months vs 8.2 months with placebo....

Treatment with niraparib boosted the duration of PFS vs placebo across the biomarker subgroups examined. The greatest benefit was observed in those with HRD tumors that were BRCA mutated....

“Sustained benefit was observed with long-term follow-up, with hazard ratios that were consistent with the primary analysis regardless of biomarker status,” lead study author Antonio González-Martin, of Medical Oncology Department, Clinica Universidad de Navarra, and colleagues, wrote in a poster on the data. “In the HRD and homologous recombination–proficient [HRp] populations, respectively, a clinically meaningful 48% and 35% reduction of the risk of progression or death was observed.”

The randomized, double-blind, placebo-controlled, phase 3 trial enrolled patients with newly diagnosed ovarian cancer who were at high risk for recurrence following response to frontline platinum-based chemotherapy....

Niraparib Maintenance Produces Long-Term Benefit in Advanced Ovarian Cancer, Irrespective of HRD Status

 This is an edited version of an article written by Ryan Scott and published in OncLive Oct. 12, 2022

Frontline niraparib (Zejula) maintenance sustained a progression-free survival (PFS) benefit in patients with advanced ovarian cancer, according to updated data from the phase 3 PRIMA trial presented at the 2022 ESMO Congress.

Notably, investigators observed a PFS benefit in patients who received niraparib irrespective of homologous recombination–deficient (HRD) status, according to Antonio González-Martín, MD, PhD.

At a median follow-up of 3.5 years, findings showed that patients in the overall population treated with niraparib (n = 484) achieved a median PFS of 13.8 months vs 8.2 months for patients treated with placebo.... Additionally, patients with HRD tumors treated with niraparib (n = 245) experienced a median PFS of 24.5 months vs 11.2 months for those treated with placebo.

"Our data are contributing to the body of evidence that PARP inhibitors are changing the natural history of patients with HRD [ovarian cancer] in the frontline," González-Martín said. “Our data confirm the sustained benefit of [niraparib] in this setting. This is an alternative as monotherapy for the maintenance of patients with HRD tumors.”

Pembrolizumab Delivers Promising Results in Advanced Clear Cell Gynecologic Cancer

 This is an edited version of an article written by Jason Ryan and published in OncLive Oct. 17, 2022

Pembrolizumab (Keytruda) monotherapy induced durable clinical outcomes in heavily pretreated patients with clear cell gynecologic cancer (CCGC), according to findings from the phase 2 PEACOCC trial (NCT03425565).

Forty-eight patients were included in the analysis. The progression-free survival (PFS) rate was 43.8% (n = 21/48; 90% CI, 31.5%-56.6%) at 12 weeks, exceeding the established lower bound of 15%. Eighteen (37.5%) patients had progressive disease, and 6 (12.5%) progressed and died.

Translational sample analysis is ongoing. Investigators said these results justify further evaluation of pembrolizumab as the new standard of care for advanced CCGC.

Register NOW for Free Symposium with lunch at the Four Seasons!

 

15th Annual Learning for Living Symposium

November 19, 2022

Four Seasons Hotel Boston

 

Speakers will include:

Ursula Matulonis, MD, Leslie Garrett, MD, Katharine Esselen, MD, 

Sharon Bober, Ph.D and author Donna Wiegle will share her "Teal on Wheels" Adventure!

 

SIGN UP NOW TO RESERVE YOUR SPOTS!

 This is a FREE event for ovarian cancer patients, their caregivers, support community and those in the medical field working in gynecologic oncology.

 Continental breakfast starts at 8am.  Speaker presentations will run from 8:30 to 12:30 with breaks and the opportunity to visit our sponsors display tables.

A delicious plated lunch will be served from 12:30 to 2pm

 Valet parking is available at the hotel at no cost with thanks to our sponsors support!

Upcoming Dana-Farber Virtual Symposium

Monday, September 26^th  

 Dana-Farber Gynecologic Oncology

Virtual Symposium Series

A series of free online educational programs for patients and their loved ones

_______________

Gynecologic Oncology Roundtable

Monday, Sept. 26 | 5:30-6:30 p.m. ET

Speakers:

• Ursula Matulonis, MD, Chief, Gynecologic Oncology
• Susana Campos, MD, MPH, Gynecologic Oncology
• Rebecca Porter, MD, PhD, Gynecologic Oncology

Join Drs. Matulonis, Campos, and Porter for a round table discussion about the latest research and treatments in gynecologic cancers. Please feel free to submit your questions in advance on the Zoom registration page.

 

Register for the Gynecologic Oncology Roundtable event here.

Niraprib Maintenance Prolongs PFS in Newly Diagnosed Advanced Ovarian Cancer After Response to Chemotherapy

This is an edited version of an article written by Chris Ryan and published in OncLive July 26, 2022

Maintenance therapy with niraparib (Zejula) significantly improved progression-free survival (PFS) compared with placebo in Chinese patients with newly diagnosed advanced ovarian cancer who achieved a complete response (CR) or partial response (PR) to first-line chemotherapy, according to data from the phase 3 PRIME trial (NCT03709316).1

Among patients who achieved a CR to frontline chemotherapy, those treated with niraparib (n = 212) achieved a median PFS of 29.4 months (95% CI, 19.3–not estimable [NE]) compared with 8.3 months (95% CI, 7.3-12.0) with placebo (n = 103; HR, 0.45; 95% CI, 0.32-0.61; P < .001). In the subgroup of patients who experienced a partial response to chemotherapy, those who were treated with maintenance niraparib (n = 43) had a median PFS of 19.3 months (95% CI, 11.1-NE), vs 8.3 months (95% CI, 5.6-11.1) with placebo (n = 26; HR, 0.45; 95% CI, 0.23-0.86; P = .014).

Notably, those who were treated with niraparib and achieved a CR to first-line chemotherapy experienced a numerically longer PFS than those who experienced a PR (HR, 0.67; 95% CI, 0.43-1.05).

                                                          Ovations for the Cure

                                                         CRUISE FOR A CAUSE

Saturday, September 10, 2022

11am to 2pm

 

We are so happy to share that after a 2 year wait, we will once again be offering our Cruise for a Cause luncheon cruise aboard the beautiful Spirit of Boston.

 Relax and enjoy a wonderful buffet lunch on the Spirit of Boston.  Then have a blast on the dance floor or venture outside to the outdoor deck space and enjoy the games scattered around the boat! There is no better way to see the beautiful Boston City Skyline than from the Harbor – all while supporting a good cause!

 We have some amazing raffles, 50/50 chances and auctions going on as well!  

 Your ticket to this event will help support our Patient Service Programs which offer much needed support and services to women while they are undergoing treatment for ovarian cancer.

 GET YOUR TICKETS EARLY - YOU DON'T WANT TO MISS THE FUN!

Here It Is!! 2022 TTT Slideshow from our Retreat

 2022 TTT Slideshow

Click on this link to play the slideshow

Cancer.net publishes article by Barbara Clivio entitled "What Is Mindfulness and How Can It Help People With Cancer?"

 Please use this  link to access the article from Cancer.net. It was published July 5, 2022.

Mirvetuximab Soravtansine Displays Promising Efficacy in Platinum-Resistant Ovarian Cancer

 This is an edited version of an article by Kyle Doherty appearing in OncLive, July 2, 2022.

Patients with platinum-resistant ovarian cancer have historically been an underserved population with few effective treatment options. However, a new option for these patients whose disease harbors a high level of folate receptor α (FRα) may be emerging as the first-in-class antibody-drug conjugate mirvetuximab soravtansine displayed promising antitumor activity, according to results from the phase 3 SORAYA trial (NCT04296890) presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. ...

“The results from SORAYA position were mirvetuximab soravtansine to become a practice-changing therapy for patients with platinum-resistant ovarian cancer [that is] high-grade serous and FRα positive, in a place in treatment where patients have very few options,” said Ursula A. Matulonis, MD, in an interview with OncologyLive®.Mirvetuximab soravtansine is a well-tolerated drug for patients who have responses, and those responses are durable. They are deep responses, where we saw complete responses, which is really an unheard-of phenomenon in the treatment of platinum-resistant ovarian cancer.” ...

Based on the data from SORAYA, the FDA accepted and granted priority review to the biologic license application for mirvetuximab soravtansine and is expected to decide by November 28, 2022. To validate the findings, investigators have initiated the randomized phase 3 randomized MIRASOL trial (NCT04209855) vs investigator’s choice chemotherapy. ...

"For our patients with platinum-resistant ovarian cancer and have also received bevacizumab, their option for treatment is single-agent, nonplatinum-based chemotherapy. [This includes] topotecan and gemcitabine. These drugs typically have low response rates—12% or lower—more often than not in the single agents."

"The data that we saw from SORAYA represents a clinically meaningful anticancer activity for this patient population, who, unfortunately, have very few options. This should be a new standard of care for patients with platinum-resistant, high-grade serous ovarian cancer, where there is high FRα expression within the cancer." --Ursula A. Matulonis, MD, Chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts.

FARLETUZUMAB ECTERIBULIN SHOWS EARLY ACTIVITY IN PLATINUM-RESISTANT OVARIAN CANCER

 This is an edited version of an article by Chris Ryan published 21 June 2022 by The Clearity Foundation.

The antibody-drug conjugate (ADC) farletuzumab ecteribulin (MORab-202) demonstrated notable antitumor activity with a manageable safety profile in patients with platinum-resistant ovarian cancer, according to data from the dose-expansion portion of the phase 1 Study 101 trial (NCT03386942) presented during the 2022 ASCO Annual Meeting.

...

“We are encouraged by the clinical safety and efficacy results, as measured by the preliminary antitumor activity observed in patients with platinum-resistant ovarian cancer being treated with each dose of farletuzumab ecteribulin, and with varying levels of folate receptor-alpha [FRα] expression,” Shin Nishio, MD, PhD, lead study author and an associate professor in the Department of Obstetrics and Gynecology at Kurume University School of Medicine in Fukuoka, Japan, stated in a press release.
Farletuzumab ecteribulin is comprised of the humanized anti-FRα monoclonal antibody, farletuzumab, linked to the cytotoxic microtubule inhibitor, eribulin (Halaven). The ADC delivers the eribulin payload into cancer cells that express FRα.“Based on the data from preclinical studies, farletuzumab ecteribulin has the clinical potential to elicit a bystander effect through an enzymatically cleavable linker that releases a toxic payload from the antibody, therefore acting not only on the FRα-positive cancer cells, but also the FRα-negative cancer cells surrounding the FRα-positive cancer cells,” Nishio added. “As the field of targeted therapy continues to evolve, ADCs are anticipated to become a key modality in the treatment of recurrent, platinum-resistant disease.”

Rucaparib Maintenance Shows PFS Benefit in Ovarian Cancer, Independent of HRD Status

 This is an edited version of an article by Ariana Pelosi published in OncLive June 6, 2022.

Rucaparib elicited a significant improvement in progression-free survival outcomes vs placebo as first-line maintenance therapy in patients with ovarian cancer who responded to first-line platinum-based chemotherapy across patient subgroups.

Rucaparib (Rubraca) elicited a significant improvement in progression-free survival (PFS) outcomes vs placebo as first-line maintenance therapy in patients with ovarian cancer who responded to first-line platinum-based chemotherapy across patient subgroups in both the primary and exploratory analyses of the ATHENA-MONO trial (NCT03522246). Specifically, the PARP inhibitor demonstrated improvements in both homologous recombination deficient (HRD)-positive and HRD-negative populations, findings from which were presented at the 2022 ASCO Annual Meeting....

“Patients with measurable disease at baseline have further tumor reduction with rucaparib. [Additionally], rucaparib safety profile is consistent with prior studies,” Bradley J. Monk, MD, FACS, FACOG, professor in the Division of Gynecologic Oncology at the University of Arizona College of Medicine, medical director of the Gynecologic Program at US Oncology Research Network, and lead investigator of this study, said during the presentation.

A Sensor Sniffs for Cancer, Using Artificial Intelligence

This is an edited version of an article  published on the Clearity Foundation website on May 12, 2022.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have developed a sensor that can be trained to sniff for cancer, with the help of artificial intelligence.

Although the training doesn’t work the same way one trains a police dog to sniff for explosives or drugs, the sensor has some similarity to how the nose works. The nose can detect more than a trillion different scents, even though it has just a few hundred types of olfactory receptors. The pattern of which odor molecules bind to which receptors creates a kind of molecular signature that the brain uses to recognize a scent.

Like the nose, the cancer detection technology uses an array of multiple sensors to detect a molecular signature of the disease. Instead of the signals going to the brain, they are interpreted by machine learning — a type of computer artificial intelligence.

MSK researchers led by Kravis WiSE Postdoctoral Fellow Mijin Kim and biomedical engineer Daniel Heller, head of the Cancer Nanomedicine Laboratory at MSK, built the technology using an array of sensors composed of carbon nanotubes. Carbon nanotubes are tiny tubes, nearly 100,000 times smaller than the width of a human hair. They are fluorescent, and the light they give off is very sensitive to minute interactions with molecules in their environment.

Each nanotube sensor can detect many different molecules in a blood sample. By combining the many responses of the sensors, the technology creates a unique fluorescent pattern. The pattern can then be recognized by a machine-learning algorithm that has been trained to identify the difference between a cancer fingerprint and a normal one.

In experiments conducted on blood samples obtained from patients with ovarian cancer, the researchers found that their nanosensor detected ovarian cancer more accurately than currently available biomarker tests. (A biomarker is a particular chemical produced by tumors and spread through the blood circulation that indicates the presence of disease. In this case, the biomarker tests were ones for the ovarian cancer-related proteins CA125, HE4, and YKL40.)

The hope for patients is that researchers will develop the technology further so that it can eventually be used in the clinic to rapidly screen for early-stage ovarian cancer and many other cancers.

Need for Better Cancer Screening Tests

Tests that detect early-stage cancers using blood markers hold great promise for improving outcomes for people with cancer — especially those types, like ovarian cancer, that have few early signs or symptoms.

Several serum biomarker tests for ovarian cancer are already in use. Unfortunately, these standalone biomarker measurements have proven to be ineffective at early detection. Currently, no screening strategy can identify ovarian cancer at an early enough stage to reduce mortality.

The nanosensor approach could potentially provide a better way.

“Ovarian cancer spreads along the surfaces of the abdomen and pelvis [as opposed to through the blood], which makes finding it with a blood test especially challenging,” says MSK surgeon Kara Long Roche, who was an author on the study. “This technology could potentially find more subtle, complex changes in the blood, which may be the key to early detection — and early detection will save lives.”

To train the machine-learning algorithm, the researchers needed to collect sensor responses from many blood samples, as this method requires many examples to be accurate. In addition, samples from patients with other conditions besides ovarian cancer were used: “Certain other diseases can trick the sensor because they produce some of the same components in the blood,” says Dr. Kim, the lead author of the study.

Although the technology improves the accuracy of ovarian cancer detection over current biomarker-based methods, more work is needed to enable the detection of early-stage ovarian cancer and confirm that this test works in people.

“We won’t stop until there is a way to prevent ovarian cancer deaths,” says Dr. Heller.

Investigators Hope Oregovomab Will Show Benefit in Advanced Epithelial Ovarian Cancer

 This is an edited version of an article  written by Lindsay Fischer and published by the Clearity Foundation

A new murine monoclonal antibody B43.12 is under investigation in combination with paclitaxel and carboplatin as a treatment option for patients with advanced epithelial ovarian cancer.

Oregovomab (Ovarex) in combination with paclitaxel and carboplatin for patients with advanced epithelial ovarian cancer is being tested in the phase 3 FLORA-5 trial (NCT04498117). Oregovomab is an investigational monoclonal antibody with promising phase 2 data. Oregovomab and the FLORA-5 trial were highlighted during the 2022 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in March.

“Oregovomab is an investigational monoclonal antibody that has been studied in clinical trials for patients with ovarian cancer whose tumor cells express the tumor-associated antigen CA-125 (MUC16),” the investigators noted in a poster presentation during the meeting. “Oregovomab is a novel immunotherapy that enhances the immune response to CA-125.”

The phase 3 double-blind, placebo-controlled, multicenter study has been designed to compare the safety and efficacy of oregovomab plus chemotherapy with placebo plus chemotherapy. Patients will be randomly assigned 1:1 to receive either 2 mg of intravenous oregovomab or placebo, along with 6 standard cycles of paclitaxel/carboplatin.

Additionally, investigators will seek to confirm the clinical benefit observed in a randomized phase 2 study (NCT01616303), which demonstrated that adding oregovomab to paclitaxel and carboplatin resulted in clinically significant improvements in progression-free survival (PFS) and overall survival (OS).

Investigators noted that the trial will also seek to evaluate the role of oregovomab as a neoadjuvant chemotherapy option.

Endometriosis and ovarian cancer genetically tied

 This article is taken from ScienceDaily, March 15, 2022

University of Queensland researchers have demonstrated a genetic link between endometriosis and ovarian cancer subtypes enabling them to identify potential drug targets for therapy and increasing the understanding of both diseases.

Previous studies have shown that endometriosis sufferers have a slightly increased risk of developing epithelial ovarian cancer.

Dr Sally Mortlock and Professor Grant Montgomery from UQ's Institute for Molecular Bioscience carried out a large genetic study to identify a genetic basis for this risk with a view to better understand the biological overlap between these reproductive disorders.

"More information about how they develop, their associated risk factors, and the pathways shared between endometriosis and different types of ovarian cancer has been needed," Dr Mortlock said.

Endometriosis is a chronic debilitating disease that affects the health of 1 in 9 women of reproductive age, where tissue similar to the uterus lining grows in other parts of the body, causing pain and infertility.

"Our research shows that individuals carrying certain genetic markers that predispose them to having endometriosis also have a higher risk of certain epithelial ovarian cancer subtypes, namely clear cell and endometrioid ovarian cancer."

Dr Mortlock said that although the diseases are genetically linked, the risk of ovarian cancer for those with endometriosis is not substantially increased.

"Overall, studies have estimated that 1 in 76 women are at risk of developing ovarian cancer in their lifetime and having endometriosis increases this slightly to 1 in 55, so the overall risk is still very low," she said.

The study found genes that could be drug targets to treat both endometriosis and epithelial ovarian cancer in the future.

"We explored specific areas of DNA that increase the risk of both diseases and identified genes in ovary and uterus tissue that could be targets for therapy and may be valuable to understand the link between the disorders and to disrupt biological pathways initiating cancer."

The researchers combined large datasets comparing the genomes of 15,000 people with endometriosis and 25,000 with ovarian cancer to find an overlap in risk factors between the two diseases.

The collaboration also involved Associate Professor Kate Lawrenson at Cedars-Sinai Medical Center and Dr Siddhartha P. Kar from the University of Bristol.

FDA Grants Fast Track Designation to VB-111 for Platinum-Resistant Ovarian Cancer

This is excerpted from an article in OncLive by Chris Ryan April 22, 2022

The FDA has granted a fast track designation to VB-111 (ofranergene obadenovec), a targeted anticancer viral gene therapy, for use as a potential therapeutic option in patients with platinum-resistant ovarian cancer.
    VB-111 is designed to use a dual mechanism to target a wide range of solid tumors, including ovarian cancer. The mechanism pairs the blockade of tumor vasculature with an antitumor immune response. Prior data from a phase 1/2 trial (NCT01711970) indicated that when VB-111 was combined with paclitaxel in this patient population, it was efficacious and safe.
    Among the 21 patients enrolled to the trial, approximately half had platinum-refractory disease and half previously received treatment with antiangiogenics....
The combination is currently under further exploration in the phase 3 OVAL trial (NCT03398655), where it is being compared with paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer.
    “We are pleased to receive FDA fast track designation for [VB-111] in platinum-resistant ovarian cancer. The fast track designation can facilitate the process toward potential registration and, importantly, may help expedite the time to market for [VB-111], if approved,” Dror Harats, MD, chief executive officer of VBL Therapeutics, stated in a press release. “The readout of the PFS primary end point in the OVAL trial will be an important milestone for VBL in the second half of [2022]. We believe that, if positive, this will support a biologics license application submission to the FDA.”
OVAL recently completely enrollment of 409 patients, and the trial is being conducted at cancer centers throughout the United States, Europe, Israel, and Japan. 

2022 TTT Retreat Applications/Forms

This year our annual Turning the Tide Ovarian Cancer Retreat will be held at beautiful, Essex Woods Meeting and Retreat Center, in Essex, MA.

The links are available at the bottom of the screen for you to download the application instructions, the application itself, the health history form and the consent form. You can print it out and send it back to me via email or mail. If you have trouble opening the link or you are without the ability to print, please contact me at mastrangelom@comcast.net so that I can send you a hard copy.

The acceptance process is not first-come, first-serve. Please make sure that if you are mailing the hard copy of your forms, it must be received by Tuesday, May 24th so that we can contact you by Friday, May 27th by email or 'phone to confirm your spot. We will have a wait list available.

Do not send any payment at this time - please wait until your spot has been confirmed.

·      Again, only after you have been notified of your spot, please send your check for $250 (or any amount – we want all women to attend regardless of ability to pay) payable to: Turning the Tide Ovarian Cancer Retreats Inc.

 NOTE: If you need to request a scholarship (assistance for payment) please check the box on the application form.

We so look forward to your application! 

Here are the links to each document:

Application Instruction

Application

Health Form

Consent Form

Online tool helps ovarian cancer patients feel more in control of symptoms

This is an edited version of an article published on ScienceDaily February 8, 2022.

An online symptom management tool that harnesses the problem-solving benefits of expressive writing could help women with ovarian cancer better manage complex symptoms, according to a new study led by a University of Pittsburgh and UPMC nurse-scientist.

Published in the Journal of Clinical Oncology, the study found that patients who used nurse-led and self-directed versions of the tool reported a better sense of control over symptoms compared to enhanced usual care.

"Women with ovarian cancer experience an average of 14 concurrent symptoms, so symptom management is very complex. It can be overwhelming for patients and challenging for providers, who may not have time to address these symptoms in a typical 15-minute appointment," said lead author Heidi Donovan, Ph.D., R.N., professor of health and community systems in Pitt's School of Nursing and obstetrics, gynecology and reproductive services in the School of Medicine. "That's why we developed a symptom management approach outside of a normal clinical setting, from the comfort of a woman's own home."

According to Donovan, ovarian cancer is a "low incidence, high impact cancer." In 2022, about 20,000 women will be diagnosed with ovarian cancer in the U.S., and more than 12,000 will die. For many patients who are treated successfully, the cancer recurs after two to three years.

"There's a vast difference in quality of life between patients who manage symptoms successfully and those who don't, both throughout chemotherapy and afterwards," said Donovan, who is also director of the Gynecologic Oncology Family CARE Center at UPMC Magee-Womens Hospital. "Effective symptom management requires that patients follow directions from providers but also be willing to communicate, make adjustments and try new strategies."

Donovan and her team developed a new symptom management approach called Written Representational Intervention to Ease Symptoms, or WRITE Symptoms, which guides patients to reflect on how they experience a symptom: what causes it, what makes it worse, how it feels, how it impacts their daily life and how they've tried to manage it.

"The WRITE approach blends health psychology with educational principles," explained Donovan. "The process of talking or writing about a symptom in a systematic way can help women understand which management strategies work and which don't. Using evidence-based symptom management techniques, we then help patients develop strategies for addressing target symptoms. Later, patients review the strategies and assess if changes need to be made. It's a very iterative process."

The researchers recruited 497 patients with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer. After participants completed surveys about symptom burden, controllability and quality of life and selected three target symptoms they wanted better control of, they were randomly assigned to one of three groups.

One group completed a nurse-led version of the WRITE intervention, in which nurses guided patients through the process via an asynchronous web-based message board. The second group directed themselves through a fully computer-mediated version of WRITE. The third, or enhanced usual care group, did not complete WRITE and acted as a control.

The analysis found that both WRITE interventions improved women's sense of control over their symptoms after eight weeks, and these measures were significantly greater compared with enhanced usual care.

"To see the same benefits in both the nurse-led and fully computer-mediated versions of the program is really powerful," said Donovan. "We also found that the self-led program was much more efficient: People were able to develop a symptom management plan in about 30 minutes compared to a few weeks with the asynchronous, nurse-led version."

The researchers are now developing a mobile health app that will train family members and other caregivers to help their loved ones with ovarian cancers better manage symptoms. Based on the computer-mediated version of WRITE, the app will guide users through questionnaires and problem-solving exercises, and it will feature disease-specific modules and core modules that could apply to patients with any chronic disease. For patients who need extra support, there will also be an option to connect with providers. According to Donovan, this app could be offered to families of gynecology cancer outpatients in the next year or so.

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Materials provided by University of Pittsburgh. Note: Content may be edited for style and length.

Conjugate Therapy Produces Remissions in One-Third of Patients with Drug-Resistant Ovarian Cancer, Study Results Show

This is a news release from Dana Farber Cancer Institute, published on March 19, 2022

In a clinical trial involving patients with ovarian cancer previously treated with platinum-based chemotherapy, a novel “conjugate” therapy produced a substantially better response than standard treatments, investigators at Dana-Farber Cancer Institute...

The agent, mirvetuximab soravtansine, generated an objective response – a measurable decrease in cancer burden – in nearly 33% of patients participating in the trial. That compares with response rates in the single digits for current treatments in patients whose ovarian cancer doesn’t respond to platinum-based chemotherapy.

The novel agent is one of a growing number of antibody-drug conjugates, or ADCs, which consist of a drug linked to an antibody that directly targets the cancer cell. Mirvetuximab connects an antibody targeting the folate receptor alpha molecule on high-grade serous ovarian cancers to a drug molecule called DM4 that disrupts microtubule formation. (Microtubules are major components of the cytoskeleton that give shape and structure to cells.) The folate receptor protein is far more abundant in some tumor cells than normal cells, making it an attractive target for cancer drugs.

The trial, titled the SORAYA study, enrolled 106 patients with platinum-resistant high-grade serous ovarian cancer that highly expressed folate receptor alpha. All patients were required to have previously received bevacizumab, a drug that blocks tumors from forming blood vessels to take in more oxygen and nutrients. The participants had been treated with up to three prior treatments for their ovarian cancer.

After a median follow-up of 8.1 months, 32.4% of participants had an objective anti-cancer response, including five who had a complete response, or the disappearance of all signs of cancer. The median duration of response is currently 6.9 months.

Mirvetuximab was well-tolerated by study participants. The most common adverse side effects associated with the treatment were blurred vision, keratopathy (a non-inflammatory condition of the eye), and nausea.

“These data have the potential to be transformative for ovarian cancer patients and their physicians,” said Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at Dana-Farber and co-principal investigator of the SORAYA study, who will present the findings at the SGO. “In the platinum- resistant setting and particularly in later-line treated patients, response rates with available therapy are in the single digits with significant toxicities. With an objective response rate above 30%, a duration of response of around six months, and a treatment-related discontinuation rate of 7%, mirvetuximab shows impressive activity and tolerability for patients with platinum-resistant ovarian cancer.  These data support the future of mirvetuximab as the potential standard of care for patients with folate receptor alpha positive ovarian cancer.” 

Niraparib Plus Bevacizumab Shows Promise in High-Risk Ovarian Cancer Population

 This is a shortened version of an article written by Kyle Doherty and published in OncLive March 19, 2022

Niraparib (Zejula) in combination with bevacizumab (Avastin) was efficacious following 1 line of platinum-based chemotherapy among patients with newly diagnosed advanced ovarian cancer regardless of biomarker status, according to data from an updated analysis of the phase 2 OVARIO study (NCT03326193) presented during the 2022 SGO Annual Meeting on Women’s Cancer.

Melissa Hardesty, MD, MPH, added that combination had a safety profile consistent with the known adverse effects of each treatment as monotherapy.

At the June 16, 2021, data cutoff point, patients who received the PARP inhibitor niraparib plus the vascular endothelial growth factor-A inhibitor bevacizumab (N = 105) achieved a median progression-free survival (PFS) of 19.6 months (95% CI, 16.5-25.1). The 18-month PFS rate was 62% (95% CI, 52%-71%) and the 24-month PFS rate was 53% (95% CI, 43%-63%). Median follow-up was 28.7 months (interquartile range, 23.9-32.5).

“OVARIO enrolled a high-risk population,” said Hardesty, a gynecologic oncologist with Alaska Women’s Cancer Care in Anchorage. “More than half of the patients remained progression-free at 24 months. Clinical benefit [by PFS] was observed in the overall population, and across biomarker subgroups in a continuum.”