New Phase III Studies Seek to Expand Olaparib’s Ovarian Cancer Approval

Investigators hope a duo of just-opened phase III studies will support expanding the FDA approval of olaparib (Lynparza) in ovarian cancer, according to Ursula Matulonis, MD.

Olaparib was approved in December 2014 for the treatment of women with BRCA-positive advanced ovarian cancer following treatment with 3 or more prior lines of chemotherapy.

“With the underlying identification of BRCA mutations and maybe expanding beyond BRCA, PARP inhibitors, for sure, are the next personalized medicine for ovarian cancer,” says Matulonis.

Matulonis, medical director of Gynecologic Oncology at Dana-Farber Cancer Institute, says that the landscape of PARP inhibitors in ovarian cancer is currently changing. This modification stems from genetic testing in women for risks of developing ovarian cancer, as well as identifying different mutations within the disease.

In an interview with Targeted Oncology during the 2016 Society of Gynecologic Oncology Annual Meeting, Matulonis discusses ongoing developments with olaparib, as well as the overall future of PARP inhibitors in ovarian cancer.

TARGETED ONCOLOGY: Can you tell us about the phase II study1 of cediranib and olaparib versus olaparib alone?

MATULONIS: That trial looked at single-agent olaparib versus the combination of cediranib and olaparib. Cediranib is an oral VEGF inhibitor that inhibits VEGFR-1, -2, and -3, and olaparib is an oral PARP inhibitor. One of my junior colleagues and I showed that the median progression-free survival was longer [17.7 vs 9.0 months] for women receiving the combination versus the single agent. The PFS benefit was most notable in patients who did not have an underlying BRCA mutation [16.5 vs 5.7 months]. For those patients who had a germline BRCA mutation, the combination was fairly equivalent to single-agent olaparib [PFS: 19.4 vs 16.5 months].

The interesting thing now is that this combination is moving into 2 phase III studies—those being NRG-GY004 (NCT02446600) and NRG-GY005 (NCT02502266)—which have just opened as of February 2016.

TARGETED ONCOLOGY: What are the hopes for NRG-GY004 and NRG-GY005?

MATULONIS: Both of these studies are looking at this combination. NRG-GY004 is looking at platinum-sensitive recurrent ovarian cancer, and NRG-GY005 is looking at the combination in platinum-resistant ovarian cancer.

The hope is that for the sensitive patients, the combination will be either similar or superior to platinum-based chemotherapy. Investigators have a choice as to which doublet they want to use—whether they want carboplatin plus paclitaxel, carboplatin plus gemcitabine, or carboplatin plus liposomal doxorubicin.

In NRG-GY005, the hope is that the combination will do better than single-agent chemotherapy. The purpose of these trials is to test this concept in patients with platinum-resistant cancer, and also patients with platinum-sensitive cancer. It’s really a different type of patient and a different subset of patients that we are testing this with.

TARGETED ONCOLOGY: Could olaparib move to earlier lines of treatment for ovarian cancer?

MATULONIS: There’s a chance that it may, but it is unlikely for that to happen based on data from these 2 trials.

These 2 randomized phase III studies are really in all patients, irrespective of underlying BRCA status. Patients are being stratified for BRCA, but it’s also for patients who have wild-type BRCA as well, whereas the FDA approval is really for patients who have germline BRCA-positive ovarian cancer.

TARGETED ONCOLOGY: Could these studies result in an expanded approval from the FDA?

MATULONIS: That would be the goal if the trials turn out to be positive. The FDA would have to make the decision about the approval or not, but yes. It would expand olaparib to be used in women who don’t have an underlying BRCA mutation and for oncologists to potentially use it earlier.

TARGETED ONCOLOGY: How does olaparib fit into the discussion on the evolution of PARP targeting in gynecologic malignancies?

MATULONIS: There are really 3 ways of how to select patients for PARP inhibitor use. One of them is through germline, or somatic, BRCA testing, which has been the olaparib strategy.

There are other strategies looking at homologous recombination deficiencies or measures of homologous recombination deficiencies, usually through something called genomic scarring. Homologous recombination deficiency assays involve loss of heterozygosity, telomeric allelic imbalance, and then large-scale transitions.

Those are measures that are part of the Myriad test that is now being prospectively tested in the NOVA trial (NCT01847274), which is looking at the PARP inhibitor niraparib versus placebo in patients with platinum-sensitive recurrent ovarian cancer on the heels of receipt of platinum-based chemotherapy.

The purpose of expanding the identification of tumors responsive to BRCA is that approximately 20% to 25% of ovarian cancers either have somatic or a germline BRCA mutations. We know that, overall, about 50% of high-grade serious cancers are what we call HR-deficient or have these homologous recombination deficiency properties that would allow it to be sensitive to carboplatin or PARP inhibitors.

The purpose of these other homologous recombination deficiencies tests are to try to capture those patients who will not necessarily have a BRCA mutation, but are also going to be sensitive to carboplatin or a PARP inhibitor.

The purpose of doing these tests is to look at the tumors and see if there has been evidence of DNA-repair problems. There are these genomic scars, where breaks happen in the DNA. However, they don’t always get fixed correctly, so there’s a scar.

The more scars you have, the more evidence you have that those tumors may be more receptive to a drug such as a PARP inhibitor.

TARGETED ONCOLOGY: How would that information impact research and practice?

MATULONIS: With that kind of information, it would allow one to predict the responsiveness of a cancer to a PARP inhibitor, but it also allows that test to be embedded within a clinical trial. This way, you can prospectively not only test the drug, but also use an appropriate biomarker to tell you which patients would be appropriate for this drug or not.

To read the full article and interview by Targeted Oncology, click here.


Ovarian Cancer: Decoding Radiology Reports

Ovarian Cancer: Decoding Radiology Reports Various imaging techniques can be used to help rule out, diagnose, stage or monitor treatment for ovarian cancer, and making sense of them all can be an onerous task even for the most educated patient. Below is a basic guide to the different scans that may be used, and some of their findings that may raise suspicion for malignancy or put you at ease.

Making Sense of Ultrasound Findings

A pelvic ultrasound, which uses sound waves, is often the scan that is first used to evaluate or find an ovarian mass or tumor. Remember, tumors can be benign or malignant, so the term “tumor” only means an enlargement. What it is can’t be proven until it is removed and evaluated by a pathologist, if that is required.

If you are concerned about ovarian cancer, it is important to remember that the malignancy risk for epithelial cancer of the ovary (the most common ovarian cancer) rises with age, while the much less common germ cell or sex-cord stromal tumors can occur in the second, third and fourth decades of life.

The first language to look for is whether or not the ovarian mass or enlargement is a “simple cyst” or “complex”. Simple cysts are rarely malignant, especially if they are small. Next, if it is described as being complex, is there language which further describes what the complexity is? If it is complex because it has a “septum,” which is only a separation between several parts of a cyst, it is less likely to be malignant or cancerous. If the complexity is noted to contain nodules or “excresences” or multiple solid parts, then it is more likely to be something to be concerned about.

Next, what is the size of the mass? Although there are no clear cut-off points, simple cysts that are less than 10 centimeters (size of an orange) are unlikely to be malignant.

Finally, is there any mention of free fluid” in the pelvis? This may mean that there is “ascites” which is part of the ovarian cancer growth process. It does not prove that you have cancer, and a small amount can be a normal finding, but a lot of free fluid or “ascites” is more worrisome.

Understanding CT or CAT Scan Findings

Computed tomography is a fancy scan which uses computers to create and record absorption rates of X-ray beams in tissue and bone. These scans are used to take a closer look at whether or not cancer has spread to other areas such as lymph nodes, around the intestines,in the liver, or lungs.

Terms to look for that might signify spread of cancer include the following: ascites, metastases, carcinomatosis, lesions, omental cake, stranding, and effusion. Also, lymph nodes may be described as enlarged. The closer they are to 2 centimeters or larger, especially with “central necrosis”, the more it may represent cancer spread.

Keep in mind that scans are merely sound or X-ray shadows. They cannot absolutely diagnose, prove or disprove that you have cancer. For that a biopsy is required. When ovarian cancer is suspected, usually surgery is the next step. Needle biopsies guided by ultrasound or CAT scan are usually only performed when it is obvious that there is spread. An ovarian mass which may represent an early ovarian cancer should not be needle biopsied for fear of rupturing and spreading cancer cells.

If the CAT scans are being used to see if the cancer treatment is working, the terms described above are still the ones to look for. The key is to look for language which describes whether or not the areas of concern are getting smaller or larger. Also, look for specific language like “resolution”, “regression” or “progression” at the end of the report which may signify whether not not things are getting better or worse.

To read this entire article by About Health, click here.

Seeking Predictor of Survival in Ovarian Cancer

Residual disease at second cytoreductive surgery identified patients with ovarian cancer associated with improved progression-free (PFS) and overall survival, suggesting potential as a surrogate for survival, according to a study reported here.

Patients who had pathologic complete response (pCR, no microscopic disease) had a median PFS of 16.1 months, decreasing to 13.5 months for patients with microscopic disease at second surgery, and 11.5 months for patients with gross residual disease. Median overall survival decreased from 51.5 months to 30.8 months as residual disease status increased from pCR to gross residual tumor.

The retrospective observation suggests that residual disease at second cytoreductive surgery might offer an alternative to overall survival for evaluating the efficacy of ovarian cancer therapy and help speed up the approval process for new therapies, Peter G. Rose, MD, of the Cleveland Clinic, reported at the Society of Gynecologic Oncology (SGO) meeting.

“If the pathologic response rates following neoadjuvant chemotherapy can be reliably determined and stratified by BRCA/BRCAoid status, neoadjuvant chemotherapy followed by early surgical reassessment may be a new platform for accelerated oncology therapeutic approval in ovarian cancer,” said Rose.

In another report at the SGO meeting, data from a randomized British study showed that three cycles of neoadjuvant chemotherapy led to pCR in about 4% of patients, as compared with 18% in the study reviewed by Rose. Additionally, 10% of patients had normalization of levels of the CA-125 cancer marker, but decline in CA-125 levels had no association with disease extent at laparotomy, said Sean Kehoe, MD, of the University of Birmingham.

In a discussion that followed the two presentations, Sanjeeve Bala, MD, of the FDA, suggested that patients who were suboptimally debulked in the U.S. study might have biologically different disease as compared with the subgroup that achieved pCR. Although the results suggested a correlation of pCR with PFS and overall survival, the analysis raised questions that need to be addressed in future trials, including questions that have implications for regulatory decisions: the precise nature of the association between pCR and long-term outcome, the optimal definition of pCR, and the magnitude of pCR improvement to predict benefit.

As for the British study, Bala said the randomized trial offered the “ideal platform for establish pCR as a valid surrogate endpoint,” but he questioned whether three cycles of neoadjuvant chemotherapy are adequate.

“Neoadjuvant chemotherapy trials should incorporate pCR evaluation in all enrolled women,” said Bala. “Establishing pCR as a surrogate endpoint correlated with overall survival would be a powerful step in accelerating clinical trials and potentially drug approval.”

Rose’s presentation had its genesis in an ovarian cancer endpoints workshop held last fall, cosponsored by the FDA, American Association for Cancer Research, American Society of Clinical Oncology, and SGO. One workshop objective was to explore novel treatment designs that might facilitate discovery and regulatory approval. In particular, investigators were encouraged to examine the Gynecologic Oncology Group 152 trial with respect to surgical findings at second cytoreductive surgery.

To emphasize the lengthy process that leads to therapeutic discovery and approval, Rose noted that the GOG 152 protocol received final approval from GOG and NCI during at a meeting that ended July 19, 2003, the same day his son was born. By the time the study results were published, his son was 11 years old.

Studies in multiple types of cancer have demonstrated positive relationships between pCR achieved with neoadjuvant therapy and subsequent survival. However, limited data exist with regard to pCR, residual disease, and second cytoreductive surgery in ovarian cancer. Moreover, the few available studies have employed different chemotherapy regimens and courses/cycles of therapy, said Rose.

In GOG 152, patients who had suboptimal primary debulking received paclitaxel-cisplatin chemotherapy and then were randomized to second cytoreductive surgery or no additional surgery, followed by additional chemotherapy, which was identical in both arms.

The new analysis focused on 216 patients randomized to second cytoreductive surgery in GOG 152. At second surgery, 70.8% of patients had gross residual disease, 3.7% had microscopic disease, and 18.5% had achieved pCR. The remaining 7% of patients did not have surgery for various reasons.

The results showed a significant association between extent of disease at second surgery (pCR to gross residual) and both PFS (P=0.002) and overall survival (P=0.018).

“Secondary cytoreductive surgery is not standard of care,” Rose noted. “Therefore, the findings of this study are only thought provoking.”

Moreover, recent data from members of the National Comprehensive Cancer Network suggest that about 40% to 50% of patients with stage III-IV ovarian cancer receive neoadjuvant chemotherapy, he added.

Kehoe reported findings from a subgroup analysis of the CHORUS trial, which compared primary surgery followed by six cycles of chemotherapy versus three cycles of neoadjuvant chemotherapy followed by surgery and three more cycles of chemotherapy. The analysis focused on 252 patients randomized to initial neoadjuvant chemotherapy, of whom 217 had cytoreductive surgery.

CT scans before and after neoadjuvant chemotherapy showed that 10 patients (4.25%) pCR, 204 had no change in disease burden, and 21 had progressive disease. Findings at surgery showed that seven patients (4%) had no evidence of disease, 24 (12%) had <1 cm residual disease, and 166 (84%) had gross residual disease.

Kehoe reported that neoadjuvant chemotherapy resulted in a complete response rate of 10% as defined by serum CA-125 levels, and 34% of the patients had at least a 50% reduction in CA-125. Bala, however, noted that the FDA does not recognize CA-125 as an endpoint.

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Ovarian Cancer Care Could Be Better; How Focusing On Subtypes, Racial Disparity Improves Treatment

Ovarian Cancer Care Could Be Better; How Focusing On Subtypes, Racial Disparity Improves Treatment

As ubiquitous as cancer is, there are alarming gaps when it comes to both knowledge and understanding of the disease. This is especially true of less frequent varieties, such as ovarian cancer, which the Centers for Disease Control and Prevention (CDC) ranks the eighth most common cancer in the United States. Yet it has a death to incidence ratio that’s stunning, Dr. Jerome F. Strauss III told Medical Daily: More than half of women diagnosed will die from it.

“If you look at the 21,000 women who will receive a diagnosis this year, 14,000 are going to die,” said Strauss, the executive vice president for medical affairs and dean of Virginia Commonwealth University School of Medicine in Richmond, Va . “It’s almost an orphan disease, but it’s lethal. Most [cases] are high-grade. And they’re insidious because they start in a small number of cells.”

That’s just one of the eye openers contained in a nearly 400-page report Strauss and a committee of members put together after the CDC tasked them to assess the current state of ovarian cancer research. It covers everything from basic biology to palliative, end-of-life care. It doesn’t define the standard of care for ovarian cancers, rather it identifies the gaps and unique research opportunities — what needs to be done to achieve better screening and treatment.

We Need To Identify Different Subtypes

Though deadly, ovarian cancer can be effectively treated when doctors catch it early enough. The committee found that “roughly two-thirds of women with ovarian cancer are diagnosed in an advanced stage, which is associated with less than 30 percent overall five-year survival rate.” While the vast majority of women with ovarian cancer respond well to treatment, it generally recurs and becomes more resistant to chemotherapy.

One of the more notable gaps the report found had to do with ovarian cancer subtypes. For the most part, the general public and health care providers wrongly believe ovarian cancer is a single disease. In fact, there are different kinds. And not all ovarian cancers originate in the ovaries either; some, Strauss found, can arise in the fallopian tube and other parts of the reproductive tract before they metastasize to the ovary. Knowing there are different subtypes inspires a “framework that provides advancing research in screening detection,” Strauss said, “a major contributor to survival rate.”

That said, high-grade serous carcinoma, a type of ovarian cancer that starts in the surface layer of the ovary, makes up 70 percent of all cancer cases — it’s the most common and the most lethal form, Strauss said. There are other important subtypes, such as endometrioid cancer and clear cell cancers, but they don’t occur as frequently.

Developing a deeper understanding of the many different origins of ovarian cancers will help inform the approach pathologists and clinicians take when treating their patients. Right now, experts lack a common language or framework to identify and characterize these diseases. This in turn makes it “very difficult to identify with precision the risk factors associated with different subtypes and also potential, effective treatments,” Strauss said.

That’s not to say people aren’t currently working toward bridging these gaps. Perhaps one of the largest efforts was a study just published in The Lancet where researchers aimed to establish the effect of early detection screening methods. The results showed women who received an annual screening, either a multimodal test for levels of the protein CA-125 or a transvaginal ultrasound, were less likely to die from ovarian cancer. Memorial Sloan Kettering reports that more than 90 percent of advanced ovarian cancer cases produce CA-125, while a transvaginal ultrasound seems to be a consistent and promising screening method.

Conversely, the CDC report found that uptake of genetic screening remains alarmingly rare in spite of new knowledge that women with the gene mutations most often associated with breast cancer, BRCA1 and BRCA2, have a 39 percent increased risk of developing ovarian cancer by the age of 70, Strauss said; the gene can be passed on by either parent.

Race & Money Matter

The advancements in ovarian cancer care have benefited some women, but not all. Overall, the five-year relative survival for all types of ovarian cancer is 45 percent, a rate that has declined among African-American women, Strauss said. A 2012 study from the University of California, Irvine, found that African Americans and poor women were less likely to receive the highest standards of care, which leads to worse outcomes compared to those of white and affluent patients. Women on Medicaid and those with no insurance have a 30 percent increased risk of cancer death; poor women experience worse outcomes regardless of race, according to the research.

A separate study conducted at the University of Texas M. D. Anderson Cancer Center in Houston found that, despite its decade-long availability, a majority of women with ovarian cancer were unaware of genetic testing for BRCA1 and BRCA2 mutations. And this awareness was more profound among minority women — 69 percent of Hispanic and 88 percent of African American respondents hadn’t heard of it compared to 52 percent of white women.

Women treated by a gynecological oncologist definitely gain an advantage in survival, as do women who undergo intraperitoneal chemotherapy, Strauss said. The latter treatment is a type of chemo, sometimes called a belly bath, that has proven more effective than a standard intravenous drip of therapy. A 2007 study found that women treated by non-gynecological oncologists or surgeons who perform fewer ovarian cancer surgeries were less likely to receive recommended surgical care. The report concludes that we need more research to better understand the racial disparity in treatment.

Where Women Can Look For Help

Women should take heart that there are targeted therapies on the horizon — precision medicine and immunotherapy treatment approaches, as well as new clinical trial designs to study the efficacy of existing therapies are currently underway. More importantly, the report notes how others might support women who have been diagnosed. Nutrition, exercise, and discussion surrounding palliative care can benefit and improve quality of life.

The American Cancer Society reports that palliative care helps relieve symptoms, but it doesn’t work to cure cancer. It’s more to help the patient feel as good as they can for as long as possible once their treatment options have run out. “Your hope for a cure may not be as bright, but there is still hope for good times with family and friends — times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life,” the Society writes.

Women, their families, and all those invested in advancing ovarian cancer care — from funders of research to advocacy groups — can read the findings of the CDC’s ovarian cancer report at the Inside Knowledge campaign, a site for the latest research, risk factor calculator tools, and survivor stories.

The blanket recommendation for now is to see a doctor if you experience symptoms such as pelvic and abdominal pain, back pain, chronic tiredness, and bloating. The CDC reports that women should also see their doctor if they have abnormal bleeding from the vagina. Ovarian cancer can be a deadly disease, but not if it’s caught in time.

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Case May Be Building For Annual CA-125 Ovarian Cancer Screening

There are “tantalizing” trends toward reduced ovarian cancer deaths with annual cancer antigen 125 screening in a United Kingdom trial involving about 200,000, average-risk postmenopausal women, according to investigator Dr. Ian Jacobs of the University of New South Wales, Sydney.

From 2001-2005, a quarter of the women were randomized to annual cancer antigen 125 (CA-125) screening, with ultrasound follow-up and oncology referral as indicated; a quarter to annual transvaginal ultrasound screening and referral; and a half to no screening, as a control. Screening ended in Dec. 2011 (Lancet. 2016 Mar 5;387(10022):945-56).

Case May Be Building For Annual CA-125 Ovarian Cancer Screening

At a median follow-up of 11.1 years, there was a nonsignificant mortality reduction of 15% (95% confidence interval, –3 to 30; P = .10) with CA-125/ultrasound multimodal screening (MMS), and 11% reduction (95% CI, –7 to 27;P = .21) with ultrasound screening. A second analysis suggested a greater, though still nonsignificant, benefit after 7 years of screening, “which is typical of cancer screening trials,” Dr. Jacobs said at the annual meeting of the Society of Gynecologic Oncology.

When women who entered the trial with ovarian cancer were excluded, there was a statistically significant 20% (95% CI, –2 to 40) overall mortality reduction and 28% reduction (95% CI, –3 to 49) after year 7 in the MMS group, compared with controls (P = .021).

“The performance criteria are good” for MMS, “and the mortality data are somewhat persuasive, but not quite there yet. We need to continue follow-up for an additional 2-3 years. If the mortality reduction pans out, the health economics are probably similar to breast cancer screening. My hope is that by about 2020, we will be including ovarian cancer screening alongside breast and cervical cancer screening,” Dr. Jacobs said.

The study excluded women with previous ovarian malignancy and two or more first degree relatives with ovarian cancer. CA-125 was interpreted with the risk of ovarian cancer algorithm, which considers changes over time, with increases indicating potential problems.

Ovarian cancer was diagnosed in 338 (0.7%) women in the MMS arm, 314 (0.6%) women in the ultrasound arm; and 630 (0.6%) women in the control group. Mortality was lowest in the MMS group, with 148 (0.29%) succumbing to the disease, versus 154 (0.30%) in the ultrasound and 347 (0.34%) in the control arms.

MMS outperformed ultrasound screening on every measure, with a 25% positive predictive value, 448 false-positive operations with 345,990 screenings, one significant compilation per 23,066 screens, and compliance of 81%. MMS was also more likely to detect earlier stage disease.

With liquid biopsy and other potential screening tests coming online, “I’m pretty sure that in due course we will not be using just one test” for screening. “The dream scenario is that we end up with a panel of tests which could reduce mortality even more,” Dr. Jacobs said.

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Observation Might Be Best In Advanced-Stage, Low-Grade Ovarian CA

Surgery, chemotherapy, and radiation do not prolong survival in advanced-stage but low-grade papillary serous ovarian cancer, according to a review of 1,159 low-grade cases in the National Cancer Data Base.

Observation might be best in advanced-stage, low-grade ovarian CA

“All you are doing is exposing patients to the toxicity without any benefit. You [should] think really hard about whether or not to give [low-grade] patients radiation or chemotherapy, instead of just following them,” said investigator Dr. Allison Gockley, an ob.gyn. at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston.

Seventy-four percent of the women received platinum-based chemotherapy, but it made no difference in survival (hazard ratio, 0.94; 95% CI, 0.75 -1.19); likewise, radiation made no difference in the seven women (0.6%) who received it.

Lymphadenectomy was the only thing associated with improved survival (HR, 0.5; 95% CI, 0.4-0.7). Dr. Gockley said she suspects it was a marker for careful surgery, but even surgery didn’t improve survival in low-grade cases (HR, 0.93; 95% CI, 0.51-1.70), although most patients had an operation.

The percentages of women who had surgery, chemotherapy, and radiation were almost identical among the 24,073 advanced-stage, high-grade cases also considered in the review, except that low-grade patients were more likely to get radiation. The approaches help high-grade cases, but “it feels very unsatisfying to me to treat low-grade” patients the same way when “they obviously have” different tumor biology, Dr. Gockley said at the annual meeting of the Society of Gynecologic Oncology.

She said she’s found similar issues with early-stage uterine clear cell carcinoma. The problem is that there just aren’t much data to guide treatment in less-dangerous gynecologic cancers, so patients end up being treated like they have advanced disease. “We need to step up and focus [study] on patients with these tumors so we can have specific treatments. For a lot of these rare tumors” – advanced-stage, low-grade disease represents about 5% of ovarian cancer – “these patients would probably do better if we had supertargeted chemotherapy,” she said.

In the absence of evidence, some patients opt for aggressive treatment “because it makes them feel that they can do something to control their disease.” As for doctors, “I’ve been in rooms where it’s very highly advocated, and others where physicians are more hesitant. What happens in the end is very much about how doctors [frame] the discussion,” Dr. Gockley said.

Her institutions follow national trends; very few patients get radiation, but most get chemotherapy, sometimes three cycles instead of six, or in low dose.

She and her colleagues looked into the issue because “we’ve seen a bunch of patients on our services recently who have low-grade, advanced-stage” ovarian cancer. The investigators wanted to know how other institutions handle the situation.

Most of the low-grade patients had stage III disease, and the rest had stage IV. Their mean age at diagnosis was 54 years, 9 years earlier than for high-grade diagnoses. About half of stage III patients were alive at 10 years, vs. about 20% of stage IV patients. As expected, high-grade patients died sooner.

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Gynecologic Cancer Patients Underutilize Advance Care Directives

Fewer than half of gynecologic oncology patients surveyed at a major cancer center had completed advance care directives regarding their preferences for end-of-life care, and most of those who did had no copy of the documents in their medical records, Dr. Alaina J. Brown reported at the annual meeting of the Society of Gynecologic Oncology.

“These findings indicate there is room to improve advance directive planning documentation in our patient population,” said Dr. Brown, a fellow in gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center in Houston.

“Providers must identify and address barriers to advance care planning documentation in order to assist patients in achieving their end-of-life care goals … I think we need to focus on educating ourselves and becoming proactive about trying to have these conversations earlier in treatment instead of when a patient is quite ill and we know that they’re going to pass away within the next week or so,” she added.

Gynecologic cancer patients underutilize advance care directives

One barrier has recently been overcome by Medicare’s new policy – effective beginning this past January – of providing reimbursement for advance care planning as a separate and billable service.

In addition, Dr. Brown’s survey of 110 gynecologic oncology patients identified two significant psychological barriers to advance care planning: high levels of death anxiety and a feeling of distress that symptoms and/or treatment side effects are interfering with daily activities and relationships.

The survey showed that while 75% of the patients were familiar with advance care directives such as a living will or medical power of attorney, only 49% of subjects had actually completed those documents, and a mere 18% had a copy of an advance care directive in their medical record.

Half of the subjects had recurrent cancer, the rest were visiting the gynecologic oncology service for active surveillance. Only a minority of those with recurrent cancer had completed advance care directives.

Study participants completed two validated, self-administered questionnaire surveys: the 19-item MD Anderson Symptom Inventory (MDASI), which assesses patient-reported disease symptoms and treatment side effects during the previous 24 hours, and the 15-item Templer’s Death Anxiety Scale.

The mean MDASI Interference score, a measure of overall symptom distress and the impact of symptoms on daily life, was significantly higher in gynecologic oncology patients who hadn’t completed advance directives than in those who had. Similarly, patients who hadn’t completed advance directives scored significantly higher on the death anxiety metric.

“Patients with recurrent disease and those with increased disease symptom burden and death anxiety should be targeted for advance care planning discussions, as they may be less likely to engage in advance care planning activities,” Dr. Brown concluded.

She noted that prior research in other medical fields has shown that holding early planning discussions about end-of-life issues improves the likelihood that a patient’s final wishes will be honored, reduces utilization of hospital resources at the end of life, and reduces distress among the patient and family members. It’s important for gynecologic oncologists to step forward in this area because they are in a unique position: they often manage a cancer patient’s surgical care as well as chemotherapy and then later assist in the transition to end of life, she added.

At the conference session on palliative care where Dr. Brown presented her findings, audience members said the 49% completion rate for advance care directives that she found in her study was actually quite impressive; at many gynecologic oncology services the rates are in the 20%-25% range. The audience consensus was that much of the blame for the low rates of advance care planning documentation in their field belongs on the shoulders of gynecologic oncologists themselves.

“I would say that it’s entirely our fault,” declared session codirector Dr. Stephanie Blank of New York University.

Dr. Brown said as a result of her survey findings, she and her colleagues are working to change the institutional practice at MD Anderson such that completion of advance care directive planning directives with documentation in the medical record becomes a quality-of-care goal within the first few patient visits.

“In the past we had a social worker come to those patients who checked off a box on a form in the waiting room; now we’re trying to be more proactive about having a provider engage the patients early on,” she explained.

She reported having no financial conflicts of interest regarding her study.

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