Brielle Urciuoli

PARP inhibitors have drastically changed the treatment landscape — and outcomes – of patients with ovarian cancer. However, despite promise shown among this class of drugs, it is still unclear which agent is the best to use in the maintenance setting.

At the 2018 Society of Gynecologic Oncology Annual Winter Meeting, David O'Malley, M.D., assistant professor in the Department of Obstetrics and Gynecology at The Ohio State University Comprehensive Cancer Center, discussed the various PARP inhibitors available and offered background on the debate of which to use.

“Currently, there are two drugs that are approved, and we think there will be a third drug. Looking at those drugs and trying to figure out what to use is not yet possible,” O’Malley said in an interview with 

The two PARP inhibitors that are currently approved in the maintenance setting for ovarian cancer are Lynparza (olaparib) and Zejula (niraparib).

Not far behind those two drugs is Rubraca (rucaparib), another PARP inhibitor that improved progression-free survival (PFS) in the maintenance setting for patients with platinum-sensitive, high-grade ovarian, fallopian tube, or primary peritoneal cancer, according to results from the phase 3 ARIEL3 trial.

“I do not think those drugs will ever be compared. They all seem to have similar efficacy, and a lot of this comes down to balancing toxicity, dosing schedules, convenience, and other factors,” O’Malley said.

Lynparza is approved for two indications in ovarian cancer treatment: one for maintenance therapy regardless of BRCA mutation status, and another for when the patient has a BRCA mutation and has had three or more prior lines of therapy. 

For Rubraca, the maintenance approval is for patients who have had at least two lines of therapy and have a BRCA mutation. Both drugs are approved for platinum-sensitive patients, many of whom have a BRCA mutation.

There are also some combinations being looked at for the maintenance setting, such as Zejula plus Avastin (bevacizumab) and cediranib plus Lynparza — both of these combination therapies are being looked at in ongoing phase 3 clinical trials.

“We do not have the results on this and we are hoping to enroll patients in those trials,” O’Malley said. “Since there are so many clinical trials out there, we hope to have any eligible patient treated on a clinical trial.”

Regardless of what PARP inhibitor regimen a patient is assigned, toxicities that come along with these drugs still pose some challenges. PARP inhibitors are usually well tolerated, but there can be some cases of fatigue, as well as gastrointestinal and hematologic events that can impact a patient’s quality of life.

“There are clearly side effects that we need to balance, and we need to look at patient-reported outcomes as we move forward in trying to ascertain the best place to use these drugs,” O’Malley said.

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PARP inhibitors have drastically changed the treatment landscape – and outcomes – of patients with ovarian cancer. However, despite promise shown among this class of drugs, it is still unclear which agent is the best to use in the maintenance setting.

Examining PARP Inhibitors in the Maintenance Setting of Ovarian Cancer

It’s been well-noted that excessive alcohol consumption can lead to a slew of health effects, including an increased risk of multiple types of cancers, but what about the effects of moderate drinking?

This was the question asked — and answered &mdash; by a team of researchers at Harvard University’s T.H. Chan School of Public Health in Boston, who surprisingly found that the results differed between men and women.  

“Heavy drinking has been linked to increased risk of several cancers, including cancer of the colon, female breast, oral cavity, pharynx, larynx, liver and esophagus, and possibly to a higher risk of cancer of the stomach, pancreas, lung and gallbladder,” Edward Giovannucci, M.D., S.D., professor of nutrition and epidemiology and study author, said in an interview with 

The association between light to moderate drinking, which the Dietary Guidelines for Americans — nutrition advice published by The U.S. Department of Health and Human Services and the U.S. Department of Agriculture every five years &mdash; describes as up to one alcoholic drink per day for women, and up to two drinks per day for men, was less clear.

“We found that light to moderate drinking was associated with minimally increased risk of overall cancer,” Giovannucci said, noting that there was a difference in increased cancer risk between genders.

The risk of alcohol-related cancers was not appreciably increased for men who were light or moderate drinkers and nonsmokers, Giovannucci explained. However, female nonsmokers had an increase of alcohol-related cancer — mainly breast cancer &mdash; after consumption of up to one alcoholic drink a day. For the women who had a drink a day, the risk increase was about 15 percent.

“For women who have a family history of breast cancer, because of their higher risk, this increased risk may be even more important,” Giovannucci said.

Science has yet to pinpoint what, exactly, it is about alcohol that can lead to a higher cancer risk, but Giovannucci said that it likely has to do with the compound that alcohol breaks down to, acetaldehyde, which can be toxic.

“When we drink alcohol, it gets absorbed in the stomach and goes into the blood. Of course, people are aware that it can reach the brain,” he said. “Likewise, it can reach other organs. The way alcohol gets metabolized or break down in different organs may influence if it affects cancer risk.”

For example, Giovannucci said, evidence suggests that the bacteria in the large intestine breaks down alcohol pretty quickly, leading to high amounts of acetaldehyde, which may increase risk of cancer in that area.

Giovannucci said that it is crucial that more research be done in this field, carefully laying out the risks and benefits of light and moderate alcohol use.

“There is some evidence that light to moderate alcohol may reduce risk of heart disease and diabetes. Interestingly, this potential benefit may be stronger in women than men,” he said. “Thus, despite their higher risk of breast cancer due to alcohol, the pros and cons of alcohol for women are still unclear. Yet, at higher levels of drinking, we know that the negative effects are important.”

It’s been well-noted that excessive alcohol consumption can lead to a slew of health effects, including an increased risk of multiple types of cancers, but what about the effects of moderate drinking?
 

Even Moderate Alcohol Use Can Increase Cancer Risk

Early detection can have drastic impacts on survival and overall outcomes for patients with melanoma. Realizing this — and the fact that it can take a while to an with a dermatologist – researchers at DermaSensor are developing a startup product that allows both health care professionals and consumers to quickly and effectively check their skin lesions that might be cancerous.

“Health care professionals will be able to use this cutting-edge device to better assess skin lesions to determine whether patients need additional clinical care and reduce unnecessary treatment,” said Cody Simmons, DermaSensor’s CEO in an interview with 

The product is a handheld pen-shaped device that uses a method called elastic scattering spectroscopy, which is currently a novel method used to detect metastatic breast cancer in excised sentinel lymph nodes. Patients and providers can evaluate lesions within seconds by running the tip of the device over their skin, and then link the devise to a user-friendly smartphone app.

DermaSensor, which is based in Miami, has been developing the product since 2011 through clinical studies and collaborations with dermatologists. Currently, it has three issued patents on its technology.

According to the American Cancer Society, more than 87,000 people in the United States will be diagnosed with melanoma in 2017. More than 9,700 of those people are expected to die.  

“The survival rate at stage 4 detection is about 15 to 20 percent, compared to 97 percent when melanoma is diagnosed at stage 1,” Simmons said. “Devices like the one we are developing at DermaSensor increase access to skin cancer checks in a cost-effective way.”

While not yet commercially available in the US, the product will soon undergo its FDA pivotal study. To date, the startup has raise $4.45 million from investors, many from South Florida and New York who come from both medical and financial backgrounds.

The company recently participated in Health 2.0’s startup pitch competition and named winner in the consumer solution category.

“DermaSensor’s potential to decrease the cost of care for patients with skin cancer while improving care quality and the patient experience distinguished the company in the pitch competition,”  according to a press release from DermaSensor about the event.

In the release, Simmons said, “It is an honor to be recognized by Health 2.0 for being the most Series A ready company and for our potential to improve outcomes for skin cancer patients around the world. Our team is committed to working tirelessly to bring our skin cancer tool to the market.”

Product developers are already looking toward the future for their product.  

“DermaSensor ultimately hopes to develop a solution that enables consumers to evaluate themselves for skin cancer at home,” Simmons said.

Patients and providers can evaluate lesions within seconds by running the tip of the device over their skin, and then link the results to a user-friendly smartphone app.

Pen-Like Device May Help Detect Melanoma

Nausea, lack of appetite and anxiety are a few of the cancer-related side effects that patients can experience. To ease the burden, many of them may turn to medical marijuana, which is legal in 29 states and Washington, D.C.

A recent study conducted by researchers at the Seattle Cancer Care Alliance in Washington state, where medical and recreational marijuana use is legal, examined the popularity of cannabis in this population.

Among 926 patients surveyed, where the median age was 58, 66 percent had previously used marijuana. Further, 24 percent used it in the last year and 21 percent in the past month.

Please briefly explain the study's findings.

 spoke with study author Steven A. Pergam, M.D., M.P.H., Associate Member, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, about what the findings could mean in the broader sense of health care.

We found that close to one-quarter of patients with cancer who responded to our survey used cannabis. Those that reported active use came from a broad spectrum of patients across all age ranges and types of cancer.

Patients used cannabis primarily for physical symptoms such as pain, nausea and to help increase appetite, but, interestingly, also used it frequently for symptoms such as coping with their illness, to deal with stress or to manage depression.

Patients with cancer who completed the survey were interested in learning more about cannabis during their treatment, regardless of active use.

Finally, and perhaps most importantly, although patients wanted to get information about cannabis use during their cancer treatment from their providers, they were more likely to get this information from non-scientific sources.

Yes and no. We expected there to be a lot of interest, but at the same time we didn't have any idea what the frequency of use might be. 

We anticipated that patients would report using cannabis for nausea or as an appetite stimulant, as these symptoms are where cannabis is most frequently purported in the lay press and online forums to provide benefits.

The frequency for which patients reported using cannabis for symptoms such as dealing with stress, coping with their illness and depression was unexpected.

Why are patients drawn to using recreational marijuana?

Despite a lack of scientific evidence, more than a quarter of patients thought that cannabis was helping to treat their cancer. This indicates a need to better educate patients.

There are lots of reasons patients might choose cannabis. This is particularly challenging to answer, as decisions that are made around cancer are often very personal and likely vary between patients.

 Our data suggests, however, that only a small percentage of patients used cannabis for recreational reasons. Most used it to help manage their symptoms. 

The surveys were taken by patients in Washington, where medical and recreational use of marijuana is legal. Do you expect findings to be very different in places where it is not legalized?

What kind of overreaching message can these findings present to the medical community?

Without data from other sites around the country, this is hard to speculate. We would like to see additional studies that attempt to replicate our findings, because we don't know if these data reflect national trends or a snapshot in a community where recreational cannabis is more readily available.

We hope that these data drive providers to start asking their patients about cannabis use. It is imperative that providers engage in these conversations, no matter if it is in a state with legalized recreational or medical cannabis, or in those places where the drug remains illegal.

Cancer providers have an opportunity to help patients make informed decisions, and to avoid potential risks that might be associated with use. If we don't ask patients about cannabis, we might miss these opportunities.

In those with very weakened immune systems, such as patients with leukemia or those undergoing a bone marrow transplant, I actively discourage patient use because of the potential increased risk of fungal pneumonia. That is in contrast to a patient in palliative care, where the benefits may outweigh the risk.

What further research needs to be conducted?

It is important for patients to understand that not all cancers and treatments are the same. By discussing their use or interest in cannabis with their providers, their cancer team can help them to make more informed decisions.

We want others to replicate our study in different centers. Future studies that focus on cancer providers’ perceptions of cannabis use among their patients are also important, so that we can help tailor educational tools about cannabis and cancer for those that care for these complex patients.

Eventually, I also hope to see more rigorous clinical trials aimed at addressing the potential risks and benefits of marijuana in cancer care. The more data we have the better we will be able to educate and protect our patients.

Brielle Urciuoli

Examining PARP Inhibitors in the Maintenance Setting of Ovarian Cancer

Even Moderate Alcohol Use Can Increase Cancer Risk

Pen-Like Device May Help Detect Melanoma

Marijuana Use Popular Among Patients With Cancer

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