STATEMENT OF NEED
This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.
Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may articipate in this CE activity.
Upon completion, participants should be able to:
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METHOD OF PARTICIPATION
This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other healthcare provider relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®.
Lauren M. Green
Lee Schwartzberg, MD, an author on both studies and director of the West Cancer Center at the University of Tennessee in Memphis, said that these follow-on analyses showed that the addition of rolapitant to the CINV regimen conferred a clinically meaningful benefit with no added toxicity: “Fewer patients had vomiting and fewer had to take rescue medicine. Overall, the quality of life was better for those patients.”
He added that women are more likely to experience CINV, providing a rationale for these targeted studies focused on subsets of women with either breast or gynecologic cancer. “We’ve known this [impact] for decades,” said Schwartzberg. “Having therapies for this particular side effect is really critical in these patients.”
Rolapitant is a potent, selective NK-1 receptor antagonist, with a plasma half-life of approximately 7 days. Activation of NK-1 receptors plays a central role in CINV induced by certain chemotherapies, particularly in the delayed phase after chemotherapy administration (>24–120 hours), which clinicians have found especially challenging to treat.
CINV and AC-based Breast Cancer Chemotherapy
For the first study, investigators conducted a post-hoc analysis of a subgroup of patients with breast cancer drawn from a prior phase III rolapitant trial (Lancet Oncol. 2015;16(9):1071-1078). Of the population included in this analysis (n = 845), 680 patients (80%) received anthracycline/cyclophosphamide (AC)–based chemotherapy, and 165 patients were treated with non–AC-based chemotherapy.
All patients were given granisetron (2 mg), along with dexamethasone (20 mg) and evenly randomized to receive either 180-mg oral rolapitant or a placebo 1 to 2 hours prior to chemotherapy on the first day of administration. The granisetron and dexamethasone regimen was administered 30 minutes prior to chemotherapy on day 1 with granisetron repeated once daily on days 2 and 3.
The investigators reported that the addition of rolapitant yielded better results on the endpoint of complete response (CR) rates, defined as no emesis, no nausea, and no use of rescue medication. CR during the overall phase (0-120 hours) in the AC-based chemotherapy arm was 62.5% with rolapitant versus 53.9% with placebo (P = .024) and during the delayed phase was 66.7 and 58.8%, respectively (P = .034).
Results were similar between study arms during the acute phase (≤24 hours), at 76.0% and 76.7%, respectively.
In the much smaller, non-AC group (20% of patients), investigators reported a trend toward better control of CINV with rolapitant versus placebo across all phases: overall (64.3% vs 60.5%; P = .616), acute (85.6% vs 82.7%; P = .598), and delayed (66.7% vs 64.2%; P = .740).
Results were comparable between the rolapitant and placebo arms on the endpoint of complete protection, defined as no emesis, no use of rescue medication, and no significant nausea. Schwartzberg explained that controlling nausea remains a significant unmet need in practice and is more difficult to quantify: “Many people involved in the development of new chemotherapy-induced nausea and vomiting drugs believe that going forward, our goals for clinical trials should be the control of nausea. The bar would be set higher, because that’s the remaining need.”
Rolapitant in Women With Gynecologic Cancers
With younger age and female gender being known risk factors for CINV, this post-hoc subgroup analysis focused on women with ovarian, uterine, or cervical cancer (n = 201) participating in separate prior phase III rolapitant research (Lancet Oncol. 2015;16(9):1079-1089).
Investigators reported that CR rates were 9% to 16% higher with rolapitant versus placebo across all phases of CINV. CR during the overall phase was 79.2% with rolapitant compared with 63.2% in the control group (P = .012). During the acute phase, CR was 91.5% and 82.1%, respectively (P = .048), and in the delayed phase, CR was 80.2% and 64.2%, respectively (P = .011).
Additionally, rates of no emesis were 13% to 15% higher in patients receiving rolapitant and 20% better for those patients on the measure of no nausea during both the overall and delayed phases.
Study authors noted that some women with gynecologic cancer continued to have CINV and especially nausea. Insofar as nausea remains difficult to control, however, “improvements in rates of no nausea with the addition of rolapitant were notable.”
The study, published online July 7, 2016 in JAMA Oncology, found that the technique reduced fatigue by 27% to 34% over 6 weeks. In addition, two-thirds of women in the study who performed relaxing acupressure reported having normal fatigue levels.
Researchers tested two types of acupressure— relaxing acupressure (used to treat insomnia) and stimulating acupressure (used to increase energy). They then compared these approaches with usual care involving typical sleep-management techniques.
The study followed 270 women recruited from the Michigan Tumor Registry who had survived stage 0 to 3 breast cancer and completed treatment at least 12 months earlier. Participants were randomized to relaxing acupressure (n = 94), stimulating acupressure (n = 90) or usual care (n = 86). Those chosen to do acupressure were taught within 15 minutes how to locate and stimulate the acupressure points with the correct amount of pressure. Participants were instructed to perform it at home once a day for 6 weeks.
By the end of the 6 weeks, more than half of participants using acupressure achieved normal fatigue levels: 66.2% in the relaxing acupressure group and 60.9% in the stimulating acupressure group. Relaxing acupressure also improved measures of sleep quality, including disrupted sleep and overall quality of life. With usual care, only 31.3% of women had normal fatigue levels.
At week 10, 56.3% of women in the relaxing acupressure arm of the study maintained normal fatigue levels, as did 60.9% in the stimulating acupressure arm of the study, compared with 30.1% in the usual care group.
Some women reported experiencing slight bruising on the sites where they were applying pressure, and 1 woman withdrew from the study as a result of this complaint. About 12% of the women stopped participating in the study because they found acupressure to be too time consuming.
Prior research suggests that acupuncture, which uses needles instead of pressure to stimulate Qi points, can be beneficial in curbing fatigue. However, it is often quite expensive and time consuming, requiring patients to visit a practitioner once or twice a week, a treatment often not covered by insurance. Acupressure, on the other hand, is simple to learn and can be done from the comforts of home.
To help people learn how to perform acupressure, the researchers are developing a mobile teaching app. They will also explore why acupressure influences fatigue, look at its effects in patients going through treatment and its impact in people with cancers other than breast.
Researchers at the University of New Mexico (UNM) Comprehensive Cancer Center compared the effects of in-person counseling and counseling done over the phone. A cohort of 988 women with an increased risk for hereditary breast or ovarian cancer was recruited, and the women were divided into two groups: one group traveled for in-person cancer genetic counseling and the other received counseling over the telephone. The counseling provided was standardized across both groups, and the teaching materials sent to the women were identical.
After 1 year, the women were assessed based on their anxiety, cancer-related distress, mental and physical health-related quality of life, how much control and how informed they felt about their risk and medical recommendations.
Both groups benefited similarly from genetic counseling. The only significant difference was in the rate of test uptake, which was approximately 9% lower in the group counseled by telephone.
The researchers suggested that further testing could explore a more diverse selection of participants for evaluation. This study was limited to those with a history of cancer, as well as limited geographically (and therefore, ethnically); only patients from Utah were included in the study, and the pool was largely non-Hispanic white individuals.
Whereas test uptake was lower for the telephone group than for the in-person group, the authors noted that the overall rate of test uptake in this study was substantially lower than other studies. This could be because of the method in which participants were selected. Rather than a referral basis, they were directly recruited, and the researchers noted that provider referral for genetic counseling and testing instills a greater sense of importance of the referral in a patient.
It is estimated that less than one-third of women at risk for hereditary breast and ovarian cancer receive genetic counseling from trained cancer genetic professionals.
Moreover, due to time and cost restraints, many women in rural communities do not have access to in-person cancer genetic counseling. The researchers hope that expanding cancer genetic counseling to take place over the phone in addition to in person would extend the reach of counselors and, therefore, increase counseling accessibility among at-risk women.
Additionally, the researchers theorized that offering two options for counseling could be beneficial, because patients experience an increased perception of control when able to choose their preferred mode of counseling.
“We hope that our study’s results will help increase health insurance coverage of telephone counseling, so that more cancer patients and their family members can benefit from potentially lifesaving cancer risk information,” noted lead author Anita Kinney, PhD, RN, associate director for Cancer Control and Population Sciences at the UNM Cancer.
Jennifer Klem, PhD
Hypophysitis is a grade 3/4 irAE most frequently associated with ipilimumab (Yervoy) that can occur at an incidence up to 17%. With PD-1 and PD-L1 inhibitors, hypophysitis is less common, with an incidence of <2%.
Hypophysitis symptoms are derived from the swelling of the pituitary gland and from hormonal deficiencies. The symptoms include headache, asthenia, fatigue, nausea, weakness, lethargy, erectile dysfunction, and loss of libido. The median time to onset of hypophysitis is 11 weeks.
If hypophysitis is suspected, immune checkpoint inhibitors should be withheld and both pituitary hormones and target tissue hormones should be measured. To treat hypophysitis, high-dose glucocorticoids are used with a slow tapering to avoid relapse or an adrenal crisis. Once the steroids are tapered, hormone replacement therapy is necessary if a deficiency is present. The development of hypophysitis does not imply discontinuation of cancer treatment, and once the corticosteroid dose has been reduced, treatment with checkpoint inhibitors may be resumed.
Thyroid disorders caused by immune checkpoint inhibitors occur most frequently as hypothyroidism and hyperthyroidism. Most thyroid dysfunctions are not extreme or life-threatening and anticancer treatment can continue. However, thyroiditis can also occur. In patients with cancer, it may be difficult to recognize thyroid disorders as their symptoms can be mistakenly attributed to the cancer itself, or other medications. Symptoms of hypothyroidism include asthenia, constipation, dry skin, hair loss, and weight gain, and treatment typically involves daily levothyroxine.
Hyperthyroidism often presents with palpitations, increased stool frequency, heat intolerance, sweating, and weight loss. There are often diagnostic and management difficulties when dealing with hyperthyroidism. Because of this, clinicians are encouraged to consult with an endocrinologist to diagnose and manage this disorder.
Primary Adrenal Insufficiency
Primary adrenal insufficiency is uncommon but can occur in up to 4% of patients treated with an immune checkpoint inhibitor. Symptoms stem from lack of glucocorticoids and mineralocorticoids and are often nonspecific, such as nausea, weakness, fatigue, anorexia, abdominal pain, and weight loss.
Treatment of primary adrenal insufficiency (and secondary adrenal insufficiency) is based on replacing glucocorticoids. Most often, this includes oral hydrocortisone which aims to mimic the physiological circasian rhythm.
In the acute form, adrenal insufficiency can progress to adrenal crisis. Adrenal crisis commonly presents with hypovolemic shock, abdominal pain, fever, and nonspecific symptoms such as nausea, vomiting, lethargy, confusion, or coma. This requires urgent treatment with hydrocortisone, even before test results can confirm the diagnosis. It is also highly recommended that an endocrinologist be consulted for acute management, differential diagnosis and evaluation for long-term replacement needs.
In cases of adrenal insufficiency, adrenal crisis can be avoided by patient education. Patients should learn the most important concepts: how to increase the steroid dose during illness or a medical procedure, the need to obtain medical assistance if they are unable to take oral medication, and the importance of wearing a medical alert necklace or bracelet. Hydrocortisone emergency injections must be provided to patients and their families, along with proper instruction on how and when to administer them.Nurse Perspective
Kathleen Madden RN, MSN, FNP-BC, AOCNP, AHNP
Thirty-eight percent of patients who achieved a complete response (CR) when treated with brentuximab vedotin remained in remission for more than 5 years. Of all patients enrolled on the study, 9% have remained in long-term remission without a consolidative allogeneic transplant, the authors noted. The findings suggest that brentuximab vedotin could lead to a cure in select patients with classical Hodgkin lymphoma.
“For a patient population that typically only sees an overall survival of 1 to 2 years after relapse from autologous stem cell transplantation, the fact that we can report such durable results after 5 years is incredible,” said lead author Robert Chen, MD, of City of Hope Cancer Research Center.
In the open-label study, 102 patients were intravenously treated with brentuximab vedotin at 1.8 mg/kg every 3 weeks for up to 16 cycles. Patients had CD30-positive relapsed/refractory disease and failed on hematopoietic autologous stem cell transplantation (ASCT). Prior to enrollment, patients had failed to achieve remission on a median of 3.5 treatments, including stem cell transplant. Patients were monitored from their
initial response until disease progression or death. The 5-year progression-free survival (PFS) rate was 22%. The median OS and PFS rates were 40.5 months (95% CI, 28.7-61.9) and 9.3 months (95% CI, 7.1-12.2), respectively. Patients who achieved a CR (n = 34) had estimated OS and PFS rates of 64% (95% CI, 0.48-.080) and 52% (95% CI, 0.34-.069), respectively.
A total of 13 patients remained in follow-up and were reported to still be in remission at the end of the study. Of these patients, four underwent consolidative hematopoietic allogeneic stem cell transplant. Nine patients remained in a sustained CR without any additional treatment.
Fifty-six patients experienced treatment-emergent peripheral neuropathy, which resolved or improved for 88% of patients. Aside from this toxicity, the most common adverse events were fatigue, nausea, neutropenia, and diarrhea.
The monoclonal portion of brentuximab vedotin targets CD30, a protein that is found on the surface of select Hodgkin lymphoma cells. Once attached to CD30, a chemotherapy component is then released into the cancer cell. This is the first study to demonstrate encouraging long-term follow-up in this heavily pretreated population, the authors noted.
The FDA initially approved brentuximab vedotin in August 2011 for the treatment of patients with Hodgkin lymphoma after failure of ASCT or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. In August 2015, this approval was expanded to include use as a consolidation therapy following ASCT in patients with CD30-positive Hodgkin lymphoma at risk of relapse or progression.
The consolidation approval was based on the phase III AETHERA trial, in which brentuximab vedotin reduced the risk of disease progression by 43% versus placebo. The median PFS with brentuximab vedotin was 42.9 months versus 24.1 months with placebo (HR, 0.57; 95% CI, 0.40-0.81; P = .001).
In early July, the European Commission (EC) also approved brentuximab vedotin for use as a consolidation therapy. In addition to the expanded indication, the EC extended the existing conditional marketing approvals for brentuximab vedotin in Europe. This decision follows a recent positive opinion issued by the EMA’s Committee for Medicinal Products for Human Use, which means that the therapy is now approved for these indications in the European Union, Norway, Liechtenstein, and Iceland.
Brentuximab vedotin is currently being studied in a number of clinical trials, including as a treatment prior to ASCT in patients with Hodgkin lymphoma, patients with CD30-positive lymphomas, and in patients with relapsed or treatment-resistant non-Hodgkin lymphoma.
Phyllis McKiernan, MSN, APN, OCN
For their study, researchers at Colombia University’s Mailman School of Public Health analyzed data from a nationally representative sample of 538,969 adults aged 18 to 85 years who self-reported their height and weight as part of the ongoing National Health Interview Survey (NHIS) during the time period 1997 to 2014; 32,447 of the participants were cancer survivors.
Researchers found a consistently increasing burden of obesity (defined as ≥30 kg/m2 for non-Asian participants and ≥27 kg/m2 for Asians) among men and women with a history of cancer when compared with adults without a history of cancer.
Adult cancer survivors had an increase in obesity prevalence from 22.4% in 1997 to 31.7% in 2014, compared with 20.9% to 29.5% over that same timespan in adults without a history of cancer (P <.001).
This increase was more pronounced in female survivors overall, in breast and colorectal cancer survivors, and among non-Hispanic blacks. “The prevalence of obesity grew more rapidly in nearly every subgroup of colorectal and breast cancer survivors, compared with the corresponding groups of adults without a history of cancer,” the authors wrote.
Additionally, the occurrence of class I obesity (BMI: 30 to <35 kg/m2) increased in women who were cancer survivors from 13.6% in 1997 to 21.0% in 2014 exceeding that of non-survivors (12.2% to 16.6%). This trend held true across all time periods, with differences expanding over time, the authors noted.
Principal investigator Heather Greenlee, ND, PhD, assistant professor of Epidemiology at the Mailman School, explained in a statement that the populations identified “are important populations in which oncology care providers should focus weight management efforts.”
Study authors also noted that specific cancer treatments, including chemotherapy, steroid medications, and hormonal therapy, can play a role
in weight gain for survivors. It is also important, they cautioned, to consider obesity among cancer survivors not only in relation to cancer outcomes, but also in relation to other comorbid diseases.
Obesity can cause additional health hazards for cancer survivors, as it can influence other medical conditions such as diabetes, heart disease, hypertension, and hypercholesterolemia, which could affect overall survival.
The researchers on this NHIS analysis predicted that based on their findings, the US obesity burden will continue to trend upward, which will not only “increase the number of obesity-related cancers, but also result in an increased burden of obesity among cancer survivors.”
Greenlee said that these results “suggest that obesity is a growing public health burden for cancer survivors, which requires targeted interventions.
Laura Newton Rutledge, MA, RD
Department of Nutrition Sciences
University of Alabama at Birmingham
Obesity is a known risk factor for many types of cancer as well as a possible contributor to the recurrence of cancer and cancer-related and all-cause mortality. Although this article found that obesity was more prevalent in cancer survivors, many patients are motivated to make changes to improve their health after diagnosis. As healthcare professionals we should seize this opportunity to help promote positive lifestyle changes to all cancer survivors.
The American Cancer Society and the American Institute for Cancer Research recommend cancer survivors lose weight if overweight or obese but do not specify an optimal diet or dietary pattern to achieve weight loss (CA Cancer J Clin. 2012;62(4):242-274). An Obesity Expert Panel from the American College of Cardiology, the American Heart Association, and the Obesity Society published guidelines for managing obesity in adults in general in 2014 (Obesity. 2014;22(suppl 2):S5-S39). These guidelines recommend 1200-1500 kcal/day for women and 1500-1800 kcal/day for men or a 500-750 kcal/day energy (calorie) deficit. The guidelines recommend using an evidence-based diet that restricts certain food types (eg, high-carbohydrate foods, low-fiber foods, high-fat foods, etc) to create an energy (calorie) deficit by reducing food intake. Therefore, the nutrition approach can and should be individualized according to patient preference and adherence ability.
The importance of exercise should also be emphasized to cancer survivors. Many studies have suggested an inverse relationship between physical activity after a cancer diagnosis and mortality. Exercise recommendations for cancer survivors include at least 150 minutes per week of aerobic exercise and two days a week of strength training (CA Cancer J Clin. 2012;62(4):242-274).
The American Society of Clinical Oncology has developed a toolkit to provide information for healthcare providers and patients about the relationship between obesity and cancer. This toolkit includes resources to help providers address weight management, including assessment of weight status, strategies to help patients achieve behavior change, links to nutrition and exercise resources, and information regarding insurance coverage of weight management services. The toolkit can be accessed here.
Interested patients may also be referred to a registered dietitian (RD) or registered dietitian nutritionist (RDN) for nutrition counseling. Some RDs and RDNs have obtained advanced training and certifications specifically in oncology nutrition and have become a board-certified specialist in oncology nutrition. A resource to help locate RDs by area can be found through the Academy of Nutrition and Dietetics at http://www.eatright.org/find-an-expert.