FDA Grants Priority Review for Rucaparib as Ovarian Cancer Maintenance Therapy

FDA Grants Priority Review for Rucaparib as Ovarian Cancer Maintenance TherapyThe US Food and Drug Administration (FDA) has granted priority review status to rucaparib as maintenance therapy for women with recurrent ovarian cancer, according to the drug’s developer. The application is for women who are platinum sensitive, and in complete or partial response to platinum chemotherapy.

“We are pleased that we continue to make significant progress toward our goal of delivering rucaparib to a much broader population of women with advanced ovarian cancer,” said Patrick J. Mahaffy, the president and CEO of Clovis Oncology, in a press release.

The priority review was granted based on results of the ARIEL3 trial, which were published in September in Lancet. The trial was a double-blind, randomized, placebo-controlled phase III study conducted in 11 countries that included 564 patients.

All patients were in complete or partial response to platinum-based chemotherapy, and received either daily rucaparib (375 patients) or placebo (189 patients) in 28-day cycles.

In the intention-to-treat population, the median progression-free survival was 10.8 months with rucaparib and 5.4 months with placebo, for a hazard ratio of 0.36 (95% CI, 0.30–0.45; P < .0001). The drug was also significantly better specifically in patients with BRCA-mutant carcinoma, and in patients with a homologous recombination–deficient carcinoma.

Treatment-emergent adverse events of grade 3 or higher were reported in 56% of rucaparib patients and in 15% of placebo patients. Anemia with decreased hemoglobin concentration was the most common of these, occurring in 19% of rucaparib patients and in 1% of placebo patients.

In Lancet, the authors wrote that “the use of a PARP inhibitor in the maintenance treatment setting … could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.”

Rucaparib received FDA approval in December 2016 for the treatment of women with deleterious BRCA mutation–associated ovarian cancer who had received at least two prior chemotherapy regimens. The FDA has set a date of action for the new indication of maintenance therapy of April 6, 2018.

To read this full article on CancerNetwork.com, please click here.


Medical Breakthroughs: Year’s Top Health Stories

Medical Breakthroughs: Year's Top Health StoriesIt’s the season of giving and while we delight in the presents we offer and receive, the real gifts are the medical advances that honor us all. Among the biggest health stories of the year: New developments in genetics, immunotherapy, stem cell treatments, medical-technology breaks, and Alzheimer’s research.

“The key word in the current world of medical research is genetics,” Dr. Richard Stein, a renowned cardiologist and spokesperson for the American Heart Association, tells Newsmax Health. “By finding the genetic markers that put us at risk for certain conditions and diseases we can adjust lifestyle changes and provide support before a catastrophic event occurs.”

For example, one of Stein’s patients, a 22-year-old woman, passed away from sudden death syndrome, a form of cardiac arrest that often attacks people under the age of 35.

“We tested her 18-year-old brother and found that although he passed all the normal heart function tests with flying colors, he had the genetic marker for SDS and we put him on a defibrillator that would kick in if he developed potentially deadly arrhythmia,” he says.

“Finding those genetic markers and even finding ways to delay or prevent their full expression is the wave of medical research today and one of the biggest advances of this past year.”

This pattern also appears in the field of Alzheimer’s disease and dementia research says Niles Frantz, a spokesman with the Alzheimer’s Association.

“There have been significant strides in several areas of research such as biomarker advancement or early detection and lifestyle intervention to reduce risks,” he tells Newsmax Health.

Here are some highlights of the medical breakthroughs in 2017:

Genetics advances. Liquid biopsies are currently used to detect changes in people with metastatic cancers. But now scientists are developing the technology that will help physicians find cancer in its earliest, treatable stages by detecting DNA from tumors in the blood, even before symptoms appear.

New drug for ovarian and breast cancers. A new type of drug called a PARP inhibitor can sometimes delay the progression of ovarian cancer for up to two years and may also be effective against breast cancer. PARP inhibitors work by preventing cancer cells from repairing their damaged DNA after treatment. Three of these drugs are currently on the market. Zejula, the most recent PARP, was approved this year for all ovarian cancers – not only for those with genetic mutations.

Immunotherapy breakthroughs. For 100 years, the idea of enlisting body’s own natural defenses to combat cancer and other illnesses has been the dream of conventional and alternative-medicine doctors alike. Now that dream is becoming reality with advent of immune system-boosting drugs like Keytruda, used to eradicate President Jimmy Carter’s cancer last year. The Food and Drug Administration approved Keytruda for patients with a genetically linked form of lung cancer. It is the first immunotherapy drug designated as a first-line treatment for patients with advanced cancer — over chemotherapy. And many experts believe it’s just the beginning of a new era in medicine. More than 2,000 immune system-boosting agents now in development, the Cancer Research Institute reports.

Alzheimer’s risk can be reduced. The Lancet Commission’s report, presented at this year’s Alzheimer’s Association International Conference, found that more than one third of global dementia cases may be preventable through addressing lifestyle factors that impact and individual’s risk. At the same conference, experts announced promising results for a blood test for beta amyloid protein, one of the key factors associated with Alzheimer’s disease and its progression.

EKG at the touch of a sensor. Dr. Kevin Campbell, a cardiologist from North Carolina applauds the Food and Drug Administration’s approval for the Kardia Band device made by Alive Core for Apple watches. “This device allows you to record a real time EKG and continuously monitors your heart rhythm — all from a smart watch — simply by pressing your thumb on its sensor,” he tells Newsmax Health.

Easier insulin monitoring. Diabetes sufferers may no longer have to prick their fingers to draw blood to monitor their glucose levels. The Medtronic MiniMed closed-loop system is worn externally and communicates with a sensor on the abdomen, administering insulin through a pump as needed.

Keep a cool head. A hair saving device was approved by the FDA to help breast cancer patients keep their hair while going through chemotherapy treatment. It’s a scalp cooling cap which could prevent chemo-related hair loss in 800,000 Americans.

Glasses that help you breathe. Chuck Negron, a former Three Dog Night singer, suffers from chronic obstructive pulmonary disease (COPD) and emphysema. He was reluctant to go on stage with an oxygen tube up his nose and but can now breathe better using the Oxy-View eye glass frames which conceal the tubes to his nose. This device can help the 16 million Americans suffering from COPD get the oxygen they need without embarrassment.

Drug-free pain relief. President Donald Trump declared the opioid crisis a public health emergency this year, with life expectancy falling in 2017, in part due to painkiller overdoses. But an innovative new Quell pain relief band, worn around your calf, offers an alternative to dangerous drugs to eas pain. The technology taps into your natural pain blocking centers with electrodes that are controlled by an App. The electrodes last about two weeks and are replaceable.

To read this full article on NewsMax.com, please click here.

Immortality at Midnight

By: Susan Gubar

Immortality at MidnightToward the end of another unexpected year of existence, outliving a poor prognosis of late-stage cancer rouses me in the dark. Such an awakening is quite different from the fretful insomnia that accompanied the dire diagnosis. Especially in this season of celebrated miracles, it somehow thrills me to be stirring at 2 or 3 a.m. Trepidation and grief dissolve in the weird awareness (can it possibly be true?) of still being alive.

Back in 2008, I was informed by a brilliant and dismayed oncologist that I would probably die before 2013. Do those of us in extended treatment become revenants? Although like many patients I continue to curse the disease, there may be one transient byproduct of even a brief reprieve for some lucky few: Cognizance of limited time can paradoxically expand time.

In my case, this oddly gratifying wakefulness seems to have little to do with meditation, handbooks, support groups, yoga classes, breathing exercises, massage, acupuncture, flax seeds, carrot juice, green tea or vitamin C. Has hardly anything to do with being responsible, not complaining, making a nutritious supper, washing the dishes, swabbing the surfaces, taking out the garbage. Or with phoning the relatives, telling stories, not complaining, listening to their fears and wishes.

Has little to do with belief in any god or gods, with redemption or resurrection, with going to heaven or, for that matter, elsewhere. Even less to do with researchers, physicians, radiologists, surgeons, nurses or technicians — the noble professionals who must be thanked — or with scans, blood tests, with living longer or better, procedures or trials or drugs, no, not at all.

The eerie quickening might have something to do with a storm passing, tossing the trees and lighting up the night sky, and then booming farther off in the distance. But, I concede as I get up out of the bed, it might not. It could be related to a partner snoring rhythmically in the abandoned bedroom or a tune in my head, bringing back memories of twirling around on a rug when I was young, spinning so rapidly that the pattern began to whirl round and round.

In other words, it may have to do with William Carlos Williams’s poem “Danse Russe.” But not exactly because I don’t take off my clothes to dance in front of a mirror, waving my shirt above my head, though I am reveling at being vertical, wide-awake, and the spirit of the household while everyone else, here and in the neighborhood, is fast asleep. At this point, I’m not much drawn to mirrors or nakedness.

It probably is connected to the prospect of beaded bubbles winking at the brim of a glass of wine, but not necessarily. Because it can descend so oddly, with simply donning slippers as the moon silvers a shade or a tremulous tree limb shivers on a window — and I am roaming in the shadowy house, savoring the bliss, the animation and vibrancy of life, how inexplicable it is, how thoroughly meaningless and incommunicable and incommensurate.

There I am, then, my body seeded with cancer that has recurred and may return, whereas now the air is sweet and quiet, with only me conscious, and I can inch forward into futures I weave for the ones I must leave behind. May they prosper and thrive through a series of tomorrows I will not experience but cherish envisioning. For they need to find — oh, please let them find! — love elsewhere and abundantly.

Yes, here I am, not the object of concern or pity that I will become later again, as before. But at this hour — because of a shivering or a silvering — alight with the frisson of being unknown in the night’s oasis, hugging my captivated self so as to capture a sliver of exhilaration and bring back a swatch for those circumstances when I will need to remember what it was all for.

Alone but not lonely, I creep down the dim hall to study photos on a shelf: friends, children, cousins, grandchildren. All of them at various stages of evolution with their unique expressions of expectation or anxiety, curiosity or self-consciousness — standing still for the intrusive camera. Each requires a long stare. Where are they going? Will they be happy? Each elicits a smile; tears flow, but tears of joy.

There are throngs of hard to visualize faces as well, strangers who have testified. Men and women whom I have read or who have read me and found the strength to comment with wisdom, irony, grit, caveats, quibbles, disputes, rants, confessions, jokes: lusciously swirling words. Editors and copy editors, too: the scrupulous sensibilities behind the outpouring. And countless storytellers, memoirists, filmmakers, poets, photographers, singers, scholars, activists setting the record straight, working for a cure, churning up insights.

What is this inebriated euphoria? Immortality at midnight! An intuition of the rightness and beauty and uniqueness of those I know and those I do not know but reverence from afar in my singular ecstasy of simply feeling fine, feeling good, staying in that sense that here is the genius of truth and the truth of genius because pleasure and exultation pulse now in this contingent place, inside just this illumined moment of being.

To read this article on The New York Times, please click here.

Fallopian Tube Removal May Help Prevent Most Common Ovarian Cancer

Fallopian Tube Removal May Help Prevent Most Common Ovarian CancerA study published in October showed that high-grade serous ovarian carcinomas (HGSOC), which account for about 75 percent of ovarian cancers, originate with abnormal cells in the fallopian tubes an average of seven years before the disease develops. This understanding could mean that younger women at high risk for HGSOC can prevent the disease through the removal of their fallopian tubes (known as salpingectomy), delaying ovary removal and avoiding early menopause. In those who have not had their tubes removed, the knowledge could provide a window of time in which to find genetic alterations before they have turned into cancer, or while the disease is in its early stages. Novel screening techniques that could pick up abnormalities in the fallopian tubes might include types of imaging, blood-based liquid biopsies or Pap tests, the study authors wrote.

The findings “have significant implications for the prevention, early detection, and therapeutic intervention of this disease,” they wrote.

The news was summarized in November in Cancer Currents, an online blog run by the National Cancer Institute. The blog reported on the study published Oct. 23 in Nature Communications by researchers at the Johns Hopkins Kimmel Cancer Center, Dana-Farber Cancer Institute, the Perelman School of Medicine at the University of Pennsylvania and others. The lead author is Sana Intidhar Labidi-Galy, M.D., Ph.D., of Geneva University Hospital, in Switzerland.

Early detection has been difficult in HGSOC because, once the disease develops, it metastasizes within an average two years, the investigators wrote. Of the women diagnosed with it, they said, 70 percent of have advanced disease by the time the disease is found.

In the study, the researchers genetically sequenced multiple tumor samples from nine patients with HGSOC who also had lesions in their fallopian tubes, which had been removed. The researchers found that most of the genetic alterations present in the patients’ ovarian tumors were also expressed in the fallopian lesions, which had formed years earlier. Strongly tied to the development of HGSOC, they found, were cancer-associated alterations to the P53 gene in the tubes, and the lesions, known as serous tubal intraepithelial carcinomas.

The results conform with the findings of research that was conducted over a decade ago.

That research was done in women who had BRCA gene mutations, which predisposed them to ovarian cancer. When they had preventive surgery to remove their ovaries, their fallopian tubes were found to harbor lesions that could have been precursors to ovarian cancer, the team led by Labidi-Galy mentioned in its paper. Such lesions, and mutated P53, have also previously been found in the fallopian tubes of women with non-inherited advanced ovarian cancer, the team pointed out.

The researchers acknowledged that their study was small, and that more research is needed. In fact, the NCI stated, trials are being conducted in the United States and the Netherlands to determine whether prophylactic removal of the fallopian tubes, with delayed ovary removal, should be considered in women with BRCA mutations. If future studies support the current findings, other protocol changes should be made, too, the authors suggested.

For one thing, they asserted, if a woman’s fallopian tubes are removed for any reason, the organs should receive “systematic sectioning and extensive examination” by a pathologist to check for lesions that could be precursors to ovarian cancer.

“In non-(BRCA mutation) carriers, our work implies that, for women who undergo surgery for benign uterine causes, total abdominal hysterectomy and bilateral salpingectomy with sparing of the ovaries should be considered, and that bilateral salpingectomy may be a preferred contraceptive alternative to tubal ligation,” they wrote.

To read this entire article on CureToday.com, please click here.

Ovarian Cancer Stem Cells: Unraveling a Germline Connection

Ovarian Cancer Stem Cells: Unraveling a Germline ConnectionStem cells are considered the holy grail for tissue regeneration and repair, but remain an elusive phenomenon in ovarian biology. Only recently, studies have uncovered the promising potential of “ovarian stem cell differentiation into female gametes”1-3, which could be explored to address female infertility, menopause, and possibly tumor initiation. The possible contribution of stem cells present in adult tissues and organs in cancer scenario is not fully clear especially in ovarian cancer. Stochastic events leading to transformation of normal stem cells and/or progenitors may be implicated4. Epithelial ovarian cancer is the most aggressive and lethal forms of gynecological cancers affecting ∼250,000 women worldwide each year5,6. Approximately 90% of ovarian tumors are epithelial in nature, and the existence of pluripotent stem cells in the ovarian surface epithelium (OSE) layer suggests a strong correlation between origin of epithelial cancer and cancer stem cells (CSCs)7. CSCs represent a novel population (2%–5%) of tumor cells possessing unique characteristics such as self-renewal and transformation into differentiated cells, which constitute the tumor bulk. These properties impart them with an edge to survive chemotherapy, undergo enrichment, and expedite tumor progression resulting in relapse thus contributing to ultimate mortality of the affected individuals8. Existence of CSCs has been reported in various cancers, including ovarian cancer9,10 breast cancer11, Glioblastoma12, and pancreatic cancer13. In this view, their identification and development of novel combination drugs targeting not only cancer cells but also CSCs are immediate requirements9,14.

Cancer initiation and resultant propagation/invasion entail a complex series of cross talk of events at cellular and molecular levels15, while the role played by CSCs requires to be rigorously investigated. There is no consensus regarding true identity of ovarian CSCs and their signaling mechanisms, their location, precise cell(s) of origin, and their individual response to novel drugs. Moreover, the putative CSC populations with ovarian stem cell perspective have never been studied across various stages of ovarian cancer. Tissue specific CSCs have already been identified in ovarian cancer, but it remains to be determined if germline stem cells reported in normal ovaries express these pluripotent stem and CSC specific markers. To reiterate, the goal of present study was to correlate the expression of pluripotent stem cells with germ lineage markers.

Presence of germline stem cells termed “oogonial stem cells” (OGSCs)/“female germline stem cells” (FGSCs) was first put forth by Prof. Jonathan Tilly and his group in adult mice16 and later in adult mice and human ovaries17. Similarly, pluripotent stem cells have been demonstrated in adult human ovaries2,3,18-22 and mice22,23 by certain groups independently. Parallel to these reports, a pluripotent stem cell population with embryonic characteristics named very small embryonic-like stem cells (VSELs) has been identified in various adult tissues and organs. These peculiar, tiny spherical stem cells are remnants of migratory PGCs gone astray during embryogenesis as they share common markers24,25. Similarly mouse hematopoietic stem progenitor cells (HSPCs) show germline connection, and thus, a hierarchical link among murine VSELs, HSPCs, and primordial germ cells (PGCs) was recently speculated26. Likewise a germline connection with the tumors was proposed27 with pluripotent adult stem cells showing embryonic characteristics (VSELs) as the putative connecting link. These VSEL cells have been speculated to differentiate into CSC populations28,29.

VASA/DDX4 is a member of DEAD box protein family involved in processes such as embryogenesis, gametogenesis, cellular growth, division and PGC development, and so on30. Besides its multifaceted cellular functions, recently its expression was linked to tumor formation and maintenance in drosophila brain31, as well as in tumor progression and poor patient prognosis in case of epithelial ovarian cancer cells32,33. DEAD-box helicase 4 (DDX4) is also implicated in cell cycle regulation in multipotent and proliferating cells by influencing 14-3-3 sigma at G2/M checkpoint. Hence it becomes imperative to pinpoint the expression of pluripotent stem cell population(s) with germline characteristics existing within the ovarian tumors in comparison to normal ovaries and investigate their relation with other pluripotent and CSC markers.

Identification of unique gene signatures for detection of early onset, predicting patient response to treatment and their survival, has been the Achilles’ heel so far in cancer research. The known pluripotent stem cell population namely ovarian (germline) stem cells and (cancer) stem cells both were studied systematically in various stages of ovarian cancer in comparison to normal ovaries. Single and double immunolabeling experiments interestingly revealed dynamic populations of pluripotent stem cells with germline and CSC specific properties within the OSE and cortex regions of the ovary. Current study provides novel insights into the stem cell profiles in normal versus ovarian tumor tissues and consolidates the germline connection with normal stem cells, as well as CSCs.

To view the references and the article in its entirety, please click here.

Ovarian Cancer Could Be Next Application For CAR T-Cell Therapy

Ovarian Cancer Could Be Next Application For CAR T-Cell TherapyWhile CAR T-cell therapy has been proven to work for liquid—or blood—cancers, the challenge has been to apply this technology to solid tumors. That’s why Amit Kumar, PhD, president and CEO at ITUS Corporation, a San Jose, California-based cancer-focused biotechnology company, is working with researchers at Moffitt Cancer Center to determine if this therapy can be beneficial to women with ovarian cancer.

Managed Healthcare Executive (MHE) recently talked to Kumar to learn how this technology works and about the promise it holds for women diagnosed with ovarian cancer.

MHE: Tell us about using CAR T therapy for ovarian cancer and the promise it holds.
Kumar:  The reason CAR T-cell therapy works for liquid—or blood—cancers is you can engineer T cells to go after a protein called CD19 on the surface of B cells. That has been very successful with two products already approved—with Yescarta from Kite Pharma and Kymriah from Novartis Pharmaceuticals—and several products being developed in clinical trials.
In solid tumors, such as ovarian cancer, there hasn’t been any demonstration of efficacy. One of the challenges has been that it’s hard to find a target protein on the surface of solid tumors that doesn’t exist anywhere else on healthy tissue.

MHE: How could your approach help with cancer treatment?
Kumar: Our technology, which we’ve licensed from the Wistar Institute, has identified a specific protein that fits that characteristic. That means that on ovarian cells in adult women the specific receptor—or protein—that we’re targeting with our engineered T cells is called the follicle stimulating hormone receptor. This is a protein that’s found only on ovarian cells in adult women. By targeting that protein, we’re not going to have our T cells target any healthy tissue.
With our CAR T, an antibody fragment binds to the receptor—that’s where we put the follicle stimulating hormone. That’s why we think this is going to be a very positive approach to the solid tumor model, which ovarian cancer is.

MHE: Could this method of treatment be used to treat other types of cancer?
Kumar: In addition, and this is at some point in the future, there are indications that the follicle stimulating hormone receptor is found on the blood vessels of other tumors, so blood vessels that are supplying nutrients to tumors of the prostate, pancreas, and lungs.
If this therapy works on ovarian cancer, we think it has a good opportunity to work on a number of other cancers as well

MHE: How did you gain access to this technology that you’d like to use to treat ovarian cancer?
Kumar: We’re licensing this technology from the Wistar Institute, where the technology was developed through funding from the U.S. National Institutes of Health and other agencies. Now, we’re taking that technology over to the Moffitt Cancer Center, which is one of the top cancer centers in the United States and in the top five in the area of CAR T technology. They’ve invested in a tremendous amount in infrastructure to do the preclinical work as well as the clinical work on CAR T technology.
We’re going to do a sponsored research agreement, which means we’re going to fund the research there. Their researchers are going to do the work; we’re going to access all of their infrastructure, as well as the top scientists and physicians in the country that are working on CAR T.

It will cost us a little over a million dollars to do this research project that we hope will enable us to take this technology into the clinic, into clinical testing.

MHE: Who’s leading the research team that’s studying this? 
Kumar: The lead researcher is Jose Conejo-Garcia, MD, PhD, who’s a co-inventor of the technology from his time as a professor at Wistar. A little over a year ago, he moved to the Moffitt Cancer Center and is now going to take the lead on getting this technology into human trials.

MHE: Where is this treatment for ovarian cancer in its journey?
Kumar: It’s still in the preclinical stage. Conejo-Garcia and his team have published the data on this technology in mouse models, demonstrating the efficacy of this technology to treat ovarian cancer. The plan at Moffitt Cancer Center is to complete Investigational New Drug (IND-) enabling studies. We have to complete those studies, which include a toxicity study, that then we will submit to the FDA; we expect that the FDA will approve taking this to the next step, which is into human testing.

We anticipate it will take us about 18 to 24 months to complete the IND-enabling studies, which will then be submitted to the FDA. Subsequent to that, we expect to work with human ovarian cancer patients. This will most likely be refractory patients—or patients who have had every other approved therapy attempted and really don’t have much hope.

We’d like to have this treatment available for women in clinical trials by the middle to the end of 2019. Depending on how well those clinical trials and the FDA approval process go, we anticipate probably another year to two years for this therapy to be generally available. We’re still looking at three to four years at least before it becomes a product.

To read this entire article by Managed Healthcare Executive, please click here.