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®.
Jason M. Broderick
Adding the CDK 4/6 inhibitor ribociclib to frontline letrozole reduced the risk of disease progression or death by 40% in elderly patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer, according to a subgroup analysis of the phase III MONALEESA-2 trial presented at the 34th Annual Miami Breast Cancer Conference®.
The median progression-free survival (PFS) was not reached (95% CI, 19.3 months-NR) in the ribociclib arm versus 18.4 months (95% CI, 15-NR) with letrozole alone (HR, 0.608; 95% CI, 0.394-0.937). These data for elderly patients were consistent with the overall study results, in which the median PFS was not reached with the ribociclib combination versus 14.7 months with letrozole alone.
Inhibition of CDK 4/6 offers an attractive therapeutic strategy for HR-positive breast cancer. CDK 4 and 6, along with their protein regulator, cyclin D1, regulate cell-cycle progression. CDK 4/6 overexpression and amplification of the cyclin D1 gene occur frequently in HR-positive breast cancer, and increased CDK 4/6 activity, in particular, is associated with resistance to endocrine therapy.
The novel regimen was also well tolerated among the elderly subgroup, with a safety profile similar to the overall study population. Despite a higher rate of patients with an ECOG performance status of 1, the elderly population also had dose interruption and reduction rates consistent with the overall trial results.
In this subgroup analysis, lead author Lowell L. Hart, MD, Florida Cancer Specialists, et al sought to determine whether the addition of CDK 4/6 inhibition to standard treatment would improve outcomes in this population.
The multicenter, double-blind phase III MONALEESA-2 trial involved 668 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had not received prior therapy for advanced disease. All patients were treated with the aromatase inhibitor letrozole at a dose of 2.5 mg/day, and investigators randomly assigned study participants to ribociclib at 600 mg/day (3 weeks on/1 week off; n = 334) or placebo (n = 334).
The primary endpoint of the trial was PFS by investigator assessment. Secondary endpoints included overall survival, response rate, and safety. The study ended prematurely after an initial interim data analysis demonstrated a significant benefit in favor of the ribociclib arm.
Among the overall population, 295 patients were ≥65 years and 373 patients were <65 years. In the elderly patient subgroup, 150 patients were randomized to the ribociclib combination and 145 patients received letrozole alone.
Baseline characteristics were similar between the 2 treatments in the elderly patient subgroup, including mean age (70 in the ribociclib arm vs 71 in the placebo arm), ECOG performance status of 0 (53% vs 55%, respectively), ECOG performance status of 1 (47% vs 46%), bone-only metastatic disease (23% in each arm), visceral metastases (61% vs 59%) and ≥3 metastatic sites (35% vs 37%).
At the time of the analysis, 60% of patients in the ribociclib group remained on study, compared with 53% of the placebo arm. The most common reasons for discontinuation among patients who received ribociclib included progressive disease (22%), adverse event ([AE]; 9%), physician decision (3%), protocol deviation (2%), and death (1%).
Adverse event–related dose interruptions occurred in 71% of patients receiving ribociclib compared with 13% of patients randomized to placebo.
The most common all-grade AEs in elderly patients reported with the ribociclib combination versus letrozole alone included neutropenia (74% vs 5%), nausea (53% vs 29%), fatigue (37% vs 24%), leukopenia (31% vs 4%), alopecia (33% vs 17%), and diarrhea (41% vs 26%).
The authors noted that all-grade anemia rates among patients receiving ribociclib were higher in the elderly population at 26% versus 13% among patients <65 years.
All-grade elevated liver enzyme levels were reported for 17% vs 6% of elderly patients in the ribociclib and placebo arms, respectively. Grade 3 prolonged QTcF (>500 ms) occurred in 1 patient in the ribociclib arm.
On March 13, 2017, the FDA approved ribociclib for use in combination with letrozole as a frontline therapy for patients with HR-positive, HER2-negative advanced breast cancer, based on the findings from the MONALEESA-2 phase III trial.
Proper care coordination and patient education are essential to the success of delivering chimeric antigen receptor T-cell (CAR T) therapy, particularly in preparing patients for potential adverse events. A multidisciplinary team approach to education and supportive care, led by a nurse coordinator, was able to successfully implement adverse event management across 22 sites in patients with refractory diffuse large B-cell lymphoma (DLBCL) who received axicabtagene ciloleucel as part of the ZUMA-1 trial, reported Alix Beaupierre, RN, BSN, OCN, at the BMT Tandem Meetings.
In this phase I trial, a subset of 7 patients with refractory DLBCL who received axicabtagene ciloleucel demonstrated an overall response rate (ORR) of 71% and a 57% complete response (CR) rate. Grade ≥3 cytokine release syndrome (CRS) occurred in 14% of patients and grade ≥3 neurologic events in 57%.
The latest safety and efficacy data from an interim analysis reported at the meeting showed a 79% ORR and 52% CR in 52 patients overall treated with axicabtagene ciloleucel and who had at least 3 months follow-up at the August 24, 2016, data cutoff. Safety data available for 93 patients overall with at least 1 month of follow-up, showed the rate of grade ≥3 CRS to be 13% and grade ≥3 neurologic events to be 29%. There have been 3 fatal events excluding progressive disease.
All CRS events resolved except for 1 cardiac arrest. Three neurologic events were ongoing at data cutoff (grade 1 memory impairment, and 1 each of grade 1 and 2 tremor). No cases of cerebral edema were reported. Two deaths related to axicabtagene ciloleucel occurred: hemophagocytic lymphohistiocytosis and cardiac arrest in the setting of CRS.
Early into the study, it became apparent that care coordination was needed to streamline the process for the healthcare team.
“In treating these patients, nursing was originally not involved,” said Beaupierre, transplant nurse coordinator at the Moffitt Cancer Center. “There was a lot of patient and loved one distress. The patients didn’t have anything concrete to visualize telling them what they’re going to experience.
“I would say that any center considering having a CAR T program needs to make sure from day 1 that there’s a nursing coordination component for the patient. It improves their perception of the outcomes and experience.”
As a result, she and the clinical nurse specialist created an educational folder that patients were instructed to bring to all appointments. The materials in the folder explained clinical events they could expect during the course of therapy, such as central line placement and care, side effects of at-home chemotherapy, CRS, neurologic events, and neutropenic precautions, in addition to how CAR T therapy works, tips for inpatient stay, and discharge planning. The value of a caregiver in the process was also stressed. Additional education along the continuum could be maintained and accessed at any point by the patient, caregiver, and staff.
Involving the caregiver is important to increase education comprehension, to maintain patient safety during the outpatient chemotherapy phase, and to identify early side effects during the postinfusion hospitalization to set in motion the proper course of action, said Beaupierre.
Each patient also received a calendar of appointments for medical testing, apheresis with line placement, and a tour of the outpatient treatment center. “It’s all mapped out; we found that the patient experience is much better with something that’s tangible,” she said.
Vigilant supportive care and tocilizumab and corticosteroids were used to treat grade ≥3 CRS and/or neurologic events. In the overall study population, 38% of patients received tocilizumab, 17% received corticosteroids, and 17% received both. With these precautions and treatments, “the axi-cel regimen has a manageable toxicity profile,” Beaupierre said. CRS and neurologic events were self-limiting and reversible in the vast majority of cases. Nurses and caregivers at the bedside played a role in early identification of symptoms.
Phyllis McKiernan, MSN, APN, OCN
The paradigms of cancer care have been shifting from cytotoxic chemotherapy and targeted therapy to immunotherapy, as promising modalities continue to develop. Early clinical data of chimeric antigen receptor T-cell (CAR T) therapy have been encouraging, and clinical trials evaluating safety and efficacy are ongoing.
For patients and their families, immunotherapy offers new hopes, but also new fears of the known and unknown side effects. As CAR T becomes more widely available, the ability to manage serious side effects should be interdisciplinary and include nursing, as the protocol reported by Alix Beaupierre and colleagues emphasizes.
Patient and family education regarding cancer therapies has been used to improve knowledge, set expectations, and alleviate fears in patients receiving both new and established treatments. For CAR T patients, the potential for cytokine release syndrome (CRS) needs to be discussed and strategies for management outlined as part of the consenting process.
Experiencing or witnessing the manifestations of CRS and neurologic sequelae can be frightening for patients and families. Understanding the potential for these reactions and knowing the team has an established approach to manage these effects gives patients confidence and helps to decrease anxiety.
When monoclonal antibody (mAb) therapy was first introduced, the reactions alarmed staff, patients, and families. Once procedures were established to manage reactions and all parties were educated, administration of MA and toxicity management has become routine and well executed. As we learn more about managing the toxicities of immunotherapy, education and consistent strategies can improve safety and decrease apprehension.
Nursing, as a key member of the care coordination team for CAR T patients, can ensure the information provided to patients is comprehensive and consistent across disciplines.
As shown with this nursing-driven protocol, the systematic approach to disseminating information and providing education to patients receiving CAR T and their families appears to have contributed to the successful management of associated toxicities, allowing patients to receive therapy and be optimally informed.
“The vaccine also reduces the incidence of moderate to severe pain, postherpetic neuralgia, and herpes zoster complications after autologous transplantation.”
In the trial, patients received V212 (n = 560) and a matching placebo (n = 564) at 0.5 mL subcutaneously approximately 30 days prior to ASCT (range, 5-60), followed by 3 subsequent injections on days 30, 60, and 90 posttransplant.
An additional arm looked at a high antigen version of the vaccine (n = 106). The high antigen arm was not included in the efficacy analysis but was part of the safety assessment.
Patient characteristics were well-balanced between the groups. In the investigational arm, the most common underlying diseases were non-Hodgkin lymphoma (42%), multiple myeloma (44%), and Hodgkin lymphoma (10%). Ninety percent of patients received conditioning chemotherapy.
Posttransplant maintenance therapy was received by one-third of patients, most commonly lenalidomide (15%), bortezomib (11%), and rituximab (7%). Posttreatment antiviral therapy was used for ≤3 months for one-third of patients, with 20% receiving these therapies for 3 to 6 months and 37% for >6 months. Twelve percent of patients did not receive antiviral therapy.
The primary endpoint was the incidence of HZ, which was deemed statistically improved if the lower end of the confidence interval was greater than 25%. Secondary endpoints focused on severity of HZ-associated pain, HZ complications, and the incidence of postherpetic neuralgia (PHN). Only those who went on to receive ASCT and the vaccine were included in the efficacy analysis.
Moderate to severe HZ-related pain was experienced by 3.5% of those in the vaccine arm versus 11.4% in the placebo group, showing teh vaccing was 69.5% effective for this endpoint (95% CI, 0.490-0.818). PHN occurred in just 0.5% of those in the vaccine arm versus 3.4% in the placebo group (83.7% efficacy; 95% CI, 0.446-0.952).
HZ complications occurred in 2.2% versus 8.2% of those in the vaccine and placebo arms, respectively (73.5% efficacy; 95% CI, 0.498-0.860).
In those <50 years, in the vaccine arm (n = 154), the HZ incidence was 4.5% compared with 17.9% in the placebo arm (n = 151). In those ≥50 years, in the vaccine group (n = 384), the HZ rate was 9.1% versus 22.4% in the placebo arm (n = 384).
Among those who received antivirals for ≤3 months, in the vaccine arm (n = 228) 9.7% had a HZ infection versus 21.3% in the placebo group (n = 239). In those treated with antivirals for 3 to 6 months, the HZ rate was 7.1% in the vaccine group (n = 310) versus 20.9% in the placebo group (n = 296).
Vaccine-related adverse events (AEs) occurred in 32.6% of patients in the investigational arm versus 12.6% in the placebo group; many of these events were associated with the high antigen vaccine.
Most of the events reported were injection site reactions (29.1% vs 6.5%). The rates of serious AEs were similar between the vaccine and placebo arms, at 32.9% and 32.7%, respectively. Serious vaccine-related AEs were 0.8% and 0.9%, in the V212 and placebo arms, respectively.
A larger phase III study is examining the efficacy, safety, and tolerability of V212 for patients with solid tumors or hematologic malignancy. The trial is comparing the vaccine with placebo across 5307 patients, with primary endpoints of reduction in HZ cases and safety.
The trial (NCT01254630) is fully enrolled with an estimated completion date in April 2017.
In a phase II single-arm study, the cumulative incidence of grade 2-4 acute GVHD at day 100 with the vorinostat combination was 22%, which met the primary endpoint of the study (target incidence of less than 28%). The historical incidence of acute GVHD despite standard immunosuppressive prophylaxis in patients receiving HSCT is 50%, said Israel Henig, MD, who presented the data at the 2017 BMT Tandem Meetings. In the study, the relapse rate at 1 year posttransplant was also low, at 19%.
Acute GVHD remains a significant barrier to a more widespread application of allogeneic HSCT for patients with hematologic malignancies. Vorinostat is a histone deacetylase inhibitor (HDAC). Inhibiting HDAC has been shown to regulate GVHD in experimental models of HSCT.
Vorinostat was safe and tolerable with no excessive toxicity or death attributable to the study drug in the phase II trial involving 37 patients. At median follow-up of 1 year, 10 patients died: 4 from relapse and 3 from acute GVHD-related infection. The cumulative incidence of grade 2-4 acute GVHD was 22% at day 100 and 22% at day 180. The cumulative incidence of grade 3-4 acute GVHD was 8% and 11% at day 100 and day 180, respectively. Estimated overall survival at 1 year was 76%.
Lauren M. Green
Patients diagnosed with head and neck or lung cancer can be particularly prone to feelings of distress, especially depression. Researchers in the Netherlands have found that using a gradual or “stepped” approach to providing psychosocial support not only improves their quality of life but is also cost-effective.
A team of investigators at the Vu Medical Center in Amsterdam sought to determine the cost-utility of a psychosocial intervention based on a stepped care (SC) model, whereby patients proceed to the next level of care only when their symptoms don’t resolve.
The approach involves 4 steps: (1) watchful waiting, (2) guided self-help via the Internet or a booklet, (3) face-to-face problem-solving therapy, and (4) specialized psychological interventions and/or psychotropic medication.
Prior cost-effectiveness studies of SC programs have shown that they improve quality-adjusted life years (QALYs) or the number of days without depression when compared with care as usual (CAU) controls. The cost-utility of the SC model has not yet been examined in patients with cancer, the researchers noted in their cost analysis (J Clin Oncol. 2017;35:314-324).
To determine eligibility for the randomized controlled trial upon which this cost utility analysis was based, patients with head and neck or lung cancer were screened for symptoms of distress, anxiety, or depression, using the Hospital Anxiety and Depression Scale (HADS). After excluding those who didn’t want to participate or were unable to be reached, 156 patients were randomized to SC (n = 75) or CAU (n = 81).
The efficacy of the SC model in this trial was analyzed and reported previously (Ann Oncol. 2016;27:1754-1760). Overall, investigators reported that patients with untreated distress in the SC group scored better than controls on the HADS, with recovery rates of 55% versus 29%, respectively, posttreatment, and 46% versus 37%, at the 12-month follow-up. Over the course of the 4 steps, 28% of those in the SC group improved after watchful waiting, 34% following the guided self-help, 9% after step 3 (problem-solving), and 17% after receiving psychotherapy and/or psychotropic medication.
For the study reported here, investigators evaluated the intervention’s economic value by calculating the mean cumulative costs and mean number of patient QALYs. The mean cumulative cost figure is based on several variables, including the cost of healthcare use and medication (direct medical costs), cost of psychological help, direct nonmedical costs (eg, support groups, transportation, and parking), and indirect nonmedical costs such as loss of productivity from employment due to absenteeism or working while in poor health.
The researchers reported that the number of QALYs was higher in the SC group, and cumulative costs were lower when compared with patients in the control group. Specifically, mean cumulative costs were €3950 (~$4196) lower using SC, and the mean number of QALYs was 0.116 higher in the SC arm versus controls.
Although study authors recommended further research to learn how stepped care can best be integrated into clinical practice, they expressed confidence about its cost-utility:
“Stepped care is highly likely to be effective,” they concluded. “In combination with findings on the efficacy of SC, it is expected to be beneficial in routine head and neck cancer and lung cancer care practice.”
Colleen O'Leary, MSN, RN, AOCNS
A diagnosis of cancer is certain to be a devastating event for any patient. Those with head and neck cancer, it can be even more alarming because of the effects of both the disease and treatments. Those with cancer depend on social supports to help them manage the fears and anxieties of a cancer diagnosis.
Patients with head and neck cancer, however, often will have difficulty chewing, swallowing, drinking, eating, and even talking. In a society where those things are seen as a means to socialize, the chance to get support from social systems is diminished. In addition, there frequently is some degree of disfigurement from the treatment of head and neck cancer that is not easily hidden, causing even more angst and isolation.
It is also not unusual for patients with head and neck cancer to have dysfunctional coping mechanisms even prior to their cancer diagnosis. When thrust into the cancer journey they must dig deep to find ways to cope. Not having strong resilient coping strategies puts them at a high risk for uncontrolled stress, anxiety, and depression.
Nurses are often the member of the healthcare team who interacts with the patients on a more intimate level where they can detect
psychosocial issues readily. Yet unfortunately, nurses might not have the knowledge or ability to employ effective interventions to improve a patient’s quality of life.
The stepped care model described in this research could give nurses the tools they need to effectively help their patients. Giving nurses the means to guide patients to useful self-help tools, along with the ability to consult further directed counseling, would inevitably improve both the patient’s coping abilities and the nurse’s sense of benevolence and caring.
In today’s world, where the economic burden of healthcare is sometimes insurmountable, advocating for interventions that are useful and cost-effective is paramount. The work of the investigators at the Vu Medical Center in Amsterdam is an important step forward for a patient population that is sometimes simply dismissed.
Lauren M. Green
A new study is providing more evidence that survivors of endometrial cancer should be closely monitored for cardiovascular disease.
These women are at higher risk for various long-term cardiovascular problems compared with their cancer-free counterparts, especially phlebitis and thrombophlebitis, pulmonary heart disease, hypeotension, and atrial fibrillation.
In fact, even after 5 to 10 years, this elevated risk persisted in endometrial cancer survivors for 18 of 70 outcomes, a team led by researchers at the Huntsman Cancer Institute reported at the recent 2017 Cancer Survivorship Symposium.1
Cardiovascular disease is the leading cause of death among the estimated 757,000 survivors of endometrial cancer in the United States. Against this backdrop, investigators used the Utah Population database to compare cardiovascular outcomes for 2648 survivors diagnosed with endometrial cancer between 1997 and 2012 and those of 10,503 age-matched, cancer-free counterparts. The majority of endometrial cancer cases (89.4%) were stage I or II.
For their analysis, researchers used clinical classification software to adapt ICD-9 diagnosis codes into cardiovascular disease categories. Statistical models that were adjusted for race, BMI, and comorbidity (using the Charlson Comorbidity Index) computed hazard ratios (HRs) for the cardiovascular outcomes at 2 time points: 1 to 5 years after diagnosis and 5 to 10 years. Overall, the most common late effects seen in endometrial cancer survivors were hypertension, which occurred in approximately 47% of survivors 1 to 5 years after diagnosis and 33% of the survivors, 5 to 10 years later.
Diseases of the heart occurred in approximately 36% and 25% of survivors at the 2 respective time points; diseases of lymphatics in approximately 24% and 14%, respectively, and diseases of arteries, arterioles, and capillaries, in 19% and 14%.
The comparative risk analysis showed that at the 1-5 year–interval, phlebitis and thrombophlebitis posed the highest cardiovascular risk for endometrial cancer survivors (HR, 3.11; 99% CI, 1.83-5.28). Other high-risk outcomes observed were lymphatic diseases (HR, 1.89; 99% CI, 1.64-2.19), hypotension (HR, 1.85%; 99% CI, 1.29-2.65), pulmonary heart disease (HR, 1.71; 99% CI, 1.24-2.36), and hypertension with complications (HR, 1.66; 99% CI, 1.17-2.35).
Notably, the elevated risk for this population held 5 to 10 years later for 18 of 70 outcomes overall.
"This study presents sufficient evidence to suggest that increased monitoring is necessary for women diagnosed with endometrial cancer in the first several years after diagnosis, and out 10 years as well," study authors concluded.
Currently no globally accepted guidelines are in place for follow-up cardiac monitoring in cancer survivors, despite the fact that cancer treatments can lead to various cardiovascular toxicities, such as left ventricular dysfunction and radiation-induced heart disease, according to researchers on a related study presented at the survivorship symposium.2 They reported on a 2-part cardiac assessment protocol, building on consensus statements from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
In providing a rationale for their study, the research team from New York Presbyterian/ Lawrence Hospital, Northwestern Medicine, and the Lurie Comprehensive Cancer Center, pointed to the “particularly concerning effect” posed by cancer therapy–related cardiac dysfunction now that survivors are living longer.
Although researchers said more data are needed to assess how well the protocol measures long-term cardiac and survival outcomes, the first assessment tool they developed shows potential for deployment in the pretreatment setting by a clinician when agents known for cardiotoxicity are part of the treatment plan. The second part would be used to stratify cardiac risk and develop an appropriate monitoring plan during survivorship.
1. Soisson SP, Ganz PA, Rowe KG, et al. Cardiovascular late effects among endometrial cancer survivors in a cohort study. J Clin Oncol. 2017;(suppl 5S; abstr 131).
2. Veneruso A, Slocum MR, Kircher SM, et al. Developing a cardiac monitoring plan in at-risk cancer survivors. J Clin Oncol. 2017;(suppl 5S; abstr 133).
Marieta Branis, DNP, ANP, NP-C
Improvements in medical technology have opened new horizons for the treatment and management of patients with endometrial cancer. Over the past 10 years, endometrial cancer has become an increasingly treatable disease, with an increased number of women living in the United States with a previously diagnosed endometrial cancer. A shift in the approach to care is occurring in the gynecologic oncology community, with the focus on cancer survivorship and close monitoring of long-term side effects of cancer treatments.
According to this study by Soisson et al (2017), cardiovascular disease has been identified as the primary cause of death for the survivors of endometrial cancer in this country. Endometrial cancer treatments such as chemotherapy, radiation, and surgery, may result in long-lasting cardiovascular dysfunctions, such as pulmonary heart disease, hypertension, atrial fibrillation, left ventricular dysfunction, etc. The study brings awareness to the lack of survivorship care guidelines regarding monitoring for cardiac toxicities in the survivors of endometrial cancer for the first 5-10 years following their treatment.
With an increased number of women surviving endometrial cancer diagnosis and treatment, the need for incorporating comprehensive survivorship care plans in clinical practice is recognized as a necessity and a challenge for gynecologic oncology practitioners.