STATEMENT OF NEED

The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.

TARGET AUDIENCE

Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

OVERALL EDUCATIONAL OBJECTIVES

Upon completion, participants should be able to:

• Describe new preventive options and treatments for cancer patients
• Identify options for individualizing the treatment for cancer patients
• Review new evidence to facilitate survivorship and supportive care for cancer patients

ACCREDITATION STATEMENT

Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.

DISCLOSURES

The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.

METHOD OF PARTICIPATION

• Read the articles in this section in its entirety.
• Go to www.dannemiller.com/onn-apr-2014.
• Complete and submit the CE posttest and activity evaluation.
• Print your Certificate of Credit.

This activity is provided free of charge to participants.

Breast Cancer

Trastuzumab/Eribulin Combo Safe and Effective in HER2-Positive Breast Cancer

The first-line combination of trastuzumab and eribulin mesylate demonstrated an objective response rate (ORR) of 71.2% with a median progression-free survival (PFS) of 11.6 months in patients with HER2-positive advanced breast cancer, according to final results from a phase II study presented in a poster session at the 31st Annual Miami Breast Cancer Conference (MBCC) held March 6-9, 2014.

“Patients that have HER2-positive disease are now being treated with pertuzumab and trastuzumab in the first-line, T-DM1 in the second-line, at some point maybe lapatinib, or maybe capecitabine plus lapatinib,” said Debu Tripathy, MD, professor of Medicine and co-leader of the Women’s Cancers Program at Norris Comprehensive Cancer Center at the University of Southern California, in an interview with OncLive TV at MBCC. “Many of these patients are candidates for even further therapy. They’re still in good shape and they’ll still potentially be responsive to other treatments. This is where we may need further chemotherapy-partner data.”

The study enrolled 52 patients with locally recurrent or metastatic HER2-positive breast cancer. Approximately half of the patients enrolled had received treatment with chemotherapy and 42.3% of patients had received prior trastuzumab or lapatinib.

On days 1 and 8, patients received eribulin at 1.4 mg/m² with trastuzumab at a loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses on day 1 of every 21 days for 6 cycles. The primary endpoint was ORR with secondary endpoints examining safety and PFS.

The ORR was 71.2% (95% CI, 56.9-82.9), with three patients experiencing a complete response (5.8%) and 34 patients with a partial response (65.4%) by investigator assessment. The stable disease rate was 25% (13 patients) for a total disease control rate of 96.2% (95% CI, 86.8-99.5).

The median time to a complete or partial response with the combination was 1.3 months (95% CI, 1.2-1.4) with a median duration of response of 11.1 months (95% CI, 6.7- 17.8). The 12-month PFS rate was 49%.

A total of 45 patients completed the full six cycles of treatment. Nine patients discontinued or stopped treatment, including one treatmentrelated death due to chronic heart failure. Overall, the toxicity was consistent with established safety profiles for eribulin and trastuzumab.

“One of the challenges is to make sure we’re not creating a new problem for our patients when they’re on long-term therapy,” said Tripathy. “We have very little data regarding the comparative neuropathy induced by taxanes and eribulin. There is some data as to how quickly it comes on, how quickly it resolves, and those characteristics seem to be favorable with eribulin.”

In the study, the most commonly occurring all-grade side effects were alopecia (88.5%), fatigue (69.2%), peripheral neuropathy (69.2%), and neutropenia (59.6%). The most common grade 3/4 adverse events were neutropenia (38.5%) and peripheral neuropathy (26.9%).

Peripheral neuropathy led to treatment discontinuations in 13.5% of patients and dose reductions in 19.2% of patients. Neutropenia led to dose reductions in 11.5% of patients and dose interruptions in 21.2% of patients.

“I think the bottom line is that you need to monitor and certainly inform patients of these side effects,” said Tripathy. “Generally speaking, the worse the toxicity gets the more long-standing it may be, and so monitoring and stopping it when it gets to be grade 2, or holding it, or attenuating dosing is critical.”

Eribulin was initially approved based on the openlabel, randomized, phase III EMBRACE trial that compared eribulin to physician’s choice in heavily pretreated patients with metastatic breast cancer. In this setting, physician’s choice included several treatments, such as hormonal therapy, palliative care, and chemotherapy. The trial found that overall survival (OS) was significantly prolonged by singleagent eribulin.

More recently, eribulin was compared with capecitabine as a second-line treatment for patients with HER2-negative metastatic breast cancer. This trial did not find a significant advantage for eribulin over capecitabine, in terms of PFS or OS. However, a subset analysis indicated a trend toward benefit with eribulin in patients with triple-negative breast cancer, which is currently an area of unmet need.

“In later lines of therapy, we do know that eribulin is a drug that has been shown to confer a survival advantage, and it was approved on that basis,” Tripathy said. “What we need is to identify markers that tell us which drug works for which patient.”

Colorectal Cancer

New DNA Stool Test Offers Higher Sensitivity Screening

A noninvasive stool DNA test may be a new option to increase rates of colorectal cancer screening, proving more sensitive in identifying colon cancer, advanced precancerous lesions, and polyps than currently available fecal immunochemical testing (FIT), according to findings of a large, multicenter study published online ahead of print March 19, 2014 in The New England Journal of Medicine.

Despite the known benefits of screening for colorectal cancer and modest increases in uptake in the last 15 years, 41% of Americans aged ≥50 years are not current with their recommended screening, according to the American Cancer Society; for certain populations, such as African Americans, screening rates are even lower.

For this study, researchers evaluated the performance of a new, multitarget DNA stool test and compared its cancer detection sensitivity with a commercially available FIT. The DNA screening tool involves quantitative molecular assays for KRAS mutations, abnormalities in methylated bone morphogenetic protein 3 (BMP3) and N-Myc downstream-regulated gene 4 (NDRG4), and β-actin. It also includes a hemoglobin immunoassay.

Specimens from 9989 individuals at average risk of colorectal cancer scheduled to undergo colonoscopy screening within 90 days of sample collection were obtained between June 2011 and November 2012 at 90 sites throughout the United States and Canada.

Of 65 study participants found to have cancer, the multitarget DNA test identified 60. Sensitivity of the DNA test was not significantly affected by cancer stage or location in the colon.

Both the DNA and the FIT test comparator were evaluated based on their detection sensitivity— defined as the true positive rate or the proportion of individuals with disease who have a positive test—in four areas: colorectal cancer (ie, adenocarcinoma); advanced precancerous lesions; polyps with high-grade dysplasia, and serrated sessile polyps measuring ≥1 cm.

The DNA test was found to be more sensitive across all four measures. For detecting colorectal cancer, sensitivity with the DNA testing was 92.3% versus 73.8% with FIT (P = .002). Sensitivity of the two tests for detecting advanced precancerous lesions was 42.4% with DNA testing versus 23.8% with FIT (P = .001); sensitivity was 69.2% and 46.2%, respectively, (P = .004) for detecting polyps with high-grade dysplasia, and 42.4% and 5.1%, respectively, (P < .001) for the detection of serrated sessile polyps.

The researchers noted, however, that although high sensitivity is the most important aspect of cancer screening, specificity (the proportion of individuals without disease who have a negative test result) also must be factored in, and here, results for FIT were better. Specificity with FIT was 94.9% to 96.4%, versus 86.6% to 89.8% for the multitarget DNA test. The majority of those with positive results, the researchers explained, will be false positives due to the low prevalence of cancer, and false-positive rates for FIT were 3.6% to 5.1% versus 10.2% to 13.4% with the DNA test. Among those with a negative colonoscopy result, the DNA test’s specificity was high—nearly 90%&mdash;though that result was still inferior to FIT specificity for this group (>96%).

Researchers also determined the number of persons who would need to be screened to detect one colorectal cancer using colonoscopy (154), multitarget DNA testing (166), and FIT (208). For the detection of one advanced precancerous lesion the numbers were 13, 31, and 55, respectively

“Detection of 92% of colon cancer is extremely high for a noninvasive test, so that a negative test result means that no further evaluation, like colonoscopy, is needed at that time,” said one of the study’s authors, David Ransohoff, MD, professor of medicine at the University of North Carolina School of Medicine and UNC Lineberger Comprehensive Cancer Center. “Having such a sensitive, noninvasive option could have an important effect on screening rates for colorectal cancer.”

On March 27, 2014, the FDA’s Molecular and Clinical Genetics advisory committee voted unanimously in support of the safety, efficacy, and positive risk-benefit profile of this noninvasive stool-based DNA test.

Nurse Perspective

Laura Metcalfe, MSN, RN, APN, C, AOCNS

John Theurer Cancer Center

Hackensack, NJ

Colorectal cancer is the third-most common type of cancer and the second leading cause of cancer death in the United States. Even so, about one in three adults aged 50 to 75 have not been tested for colorectal cancer as recommended by the US Preventive Services Task Force (USPSTF; http:// www.cdc.gov/vitalsigns).

The USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults beginning at age 50 years. The evidence is convincing that screening for colorectal cancer with any of these methods detects early-stage cancer and adenomatous, or precancerous, polyps. This is somewhat counter to what I have always believed— namely that colonoscopy is superior to the other methods, most notably as it can remove any polyps, thereby actually preventing a potential cancer from occurring. In March 2009, the American College of Gastroenterology (ACG) issued new colorectal cancer screening guidelines and stated, “Colonoscopy every 10 years, starting at age 50 years, is the preferred strategy.”

However, considering that one-third of the population who should be screened is not, we need to embrace any proven method that might improve this statistic. In a previous column for Oncology Nursing News (September 2011), I endorsed immunochemical fecal occult blood testing (iFOBT) as one way to increase screening with the understanding that any positive test could potentially lead to a colonoscopy. One drawback with iFOBT was the many false positives as well as false negatives.

The DNA test described here, if approved by the FDA, would represent an alternative or an adjunct screening method I would feel even better about recommending for those patients who either will not or cannot undergo a colonoscopy. It may be time to adopt a slogan from Australia’s 2014 bowel cancer awareness and screening campaign (testyourstool.org): “Don’t be a fool; test your stool.”

Hematologic Malignancies

Examining Distress Levels in Caregivers of Multiple Myeloma Patients

Caregivers of patients with multiple myeloma face similar challenges to those faced by the patients themselves. Multiple myeloma caregivers must assist the patient with daily activities, understand complex information about the chronic disease, attend medical appointments, and even perform complicated and technical procedures. Each relapse presents new challenges, and each episode of care creates patient and caregiver vulnerability. Because of the nature of the disease, the caregivers are often faced with physical, social, emotional, and financial problems. (Clin J Oncol Nurs. 2013;17[suppl]: 25-32).

With the majority of multiple myeloma procedures taking place in the outpatient setting, both caregivers and patients are expected to take the primary role in managing the disease. In order to manage the disease, caregivers must become educated on complex matters and with physician visits lasting around 20 minutes, it is difficult for both the patient and caregiver to understand treatment options and other disease information.

Healthcare professionals expect the patient and the caregiver to remain active in treatment decisions and to identify any treatment-related adverse events.

When a patient decides to undergo hematopoietic stem cell transplantation (HSCT), more stress is involved for both the patient and the caregiver. A prospective longitudinal study evaluated the marital adjustments, satisfaction, and dissolution among 121 patients undergoing HSCT and 117 spouses.¹ The study looked at six timepoints starting with the pretransplantation evaluation period through 5 years of follow-up.

The study found that 59 of the 121 initially married patients with a participating spouse survived to 5 years with only 7% (n = 4, two female, two male patients) of the marriages ending in dissolution. Female spouses reported a higher rate of relationship maladjustment at all timepoints during the course of the study. The authors accounted for this dissatisfaction by suggesting that women feel the need to fill the societal role of the caregiver without help and that women are more likely to be affected by the physical and psychological distress of their male partner/patient.¹

A separate study examined factors influencing the adaptation of caregivers of patients undergoing HSCT (n = 192) prior to hospitalization for transplantation, during the hospitalization following the stem cell infusion, about 1 week prior to planned discharge and 1 month after discharge.2 The patients included varied diagnoses, including multiple myeloma, with 151 patients undergoing autologous HSCT (79%) and 41 patients (21%) undergoing allogenic HSCT. The majority of caregivers participating in this study were female (72%), married to the patient (91%), working full time (58%), and Caucasian (93%).

This study found that emotional distress increased significantly between time before hospitalization and 1 month after discharge. However, the sense of personal control, spirituality, and the caregiver—patient relationship remained stable during this time.

The level of distress experienced by caregivers of patients undergoing HSCT has been shown to exceed that of the patients themselves.^1,2 Financial strain is inevitable for patients undergoing an HSCT and their caregivers. A pilot study evaluated out-of-pocket expenses for patients and caregivers (n = 22) in the first 3 months following HSCT with estimated median expenses of $2440.³ The majority of patients in this pilot study had private insurance through a managed care plan (56%), with Medicaid (20%) and Medicare (18%) being less common. Housing near the transplantation center, copayments for visits and medications, transportation, and food represented the most common sources of out-of-pocket expenses.^3,4

Numerous studies have identified unmet needs among caregivers of patients with multiple myeloma, particularly during HSCT, and clinicians have an important role to play in assisting them in identifying resources, support networks, and developing an individualized supportive care plan.

References

• Langer SL, Yi JC, Storer BE, Syrjala KL. Marital adjustment, satisfaction, and dissolution among hematopoietic stem cell transplant patients and spouses: a prospective, five-year longitudinal investigation. Psychooncology. 2010;19(2):190-200.
• Fife BL, Monahan PO, Abonour R, et al. Adaptation of family caregivers during the acute phase of adult BMT. Bone Marrow Transplant. 2009;43(12):959—966.
• Mahjail NS, Rizzo JD, Hahn T, et al. Pilot study of patient and caregiver out-of-pocket costs of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2013;48(6):865—871.
• Meehan KR, Fitzmaurice T, Root L, et al. The financial requirements and time commitments of caregivers for autologous stem cell transplant recipients. J Support Oncol. 2006;4(4):187—190.

Nurse Perspective

Melissa Baker, RN, MSN, OCN, APN-C

Adult Blood & Marrow Stem Cell Transplantation Program

John Theurer Cancer CenterHackensack, NJ

Similar to the transplant recipient, the caregiver often experiences physical symptoms of fatigue, frustration, social isolation, financial concerns, and role confusion. Caregivers may struggle to meet competing demands or find difficulty in managing multiple competing priorities. The shift in responsibility may cause role strain.

Unlike transplant recipients, caregivers are often not screened for depression or other signs of burnout. As a result of caring for the patient, oftentimes the caregivers’ own health is neglected. Caregiver burden may result in physical, social, financial, or emotional detriments. Predictors of caregiver stress include being a female caregiver, having higher levels of subjective burden, and the presence of patient symptom distress.

The effects of caregiver burnout may negatively impact patient mortality, length of hospitalization, and compliance rates. Female spouses are more likely to report relationship dissatisfaction, and are more likely to have poorer mental health, decreased social function, and sexual difficulties as a result of being a caregiver.

Nurses can decrease caregiver strain by acknowledging the commitment the caregiver is making. Nurses also provide guidance and tailored information to the caregiver, which may reduce stress levels. Establishing an educational framework, identifying available hospital or community resources, utilizing coping support networks, and engaging in role preparedness promote caregiver well-being and reduce caregiver burden.

Research to demonstrate interventions that effectively reduce caregiver burden, thereby better supporting the patient is needed. Additional research is warranted to understand the differences in caregiver experiences and develop interventions to increase caregiver coping and adaptation.

Lung Cancer

Ceritinib Shows Impressive Response Rates in ALK-Positive NSCLC

Ceritinib (LDK378), a highly selective inhibitor of ALK, demonstrated an overall response rate (ORR) of 58% and a median progression-free survival (PFS) of 7 months as a treatment for patients with ALK-positive non-small cell lung cancer (NSCLC), according to results from a single- arm phase I trial published March 27 in The New England Journal of Medicine.

“Crizotinib has become a standard treatment agent for patients with advanced, ALK-rearranged NSCLC, but patients invariably develop resistance, leaving their treatment options limited,” said Alice Shaw, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, lead author of the report. “We found ceritinib to be highly effective in the majority of crizotinibresistant patients, as well as those who had never received the drug, with mostly mild and manageable side effects.”

The trial consisted of two stages. Fifty-nine patients with NSCLC were enrolled in a doseescalation phase, which administered ceritinib from 50 mg daily to the maximum tolerated dose of 750 mg per day. In the expansion phase, 71 patients were added (n = 130), eight with other types of cancer driven by the ALK alterations. Participants took daily oral doses of ceritinib for as long as the drug was effective in suppressing tumor growth, with dosage levels being adjusted to reduce side effects. A total of 114 ALK-rearranged patients with NSCLC were treated with ceritinib at ≥400 mg per day; 80 patients were resistant or refractory to crizotinib and 34 patients were crizotinib-naïve.

The ORR for all patients was 58%, which included one complete response and 65 partial responses. Patients who had progressed during or after crizotinib therapy experienced an ORR of 56%, and those who were crizotinib-naïve had an ORR of 62%. The median PFS was 7.0 months, and the median duration of response was 8.2 months (95% CI; 6.9-11.4).

“The majority of patients in the study experienced a clinical response to LDK378. In addition, responses were seen in untreated lesions in the central nervous system in patients who previously received crizotinib,” Shaw said. “These results are important because most patients experience a disease relapse less than a year after starting crizotinib and have limited treatment options.”

The most frequent adverse events were nausea (82%), diarrhea (75%), vomiting (65%), fatigue (47%) and increased alanine aminotransferase levels (ALT [35%]). These adverse events were generally mild and resolved when treatment stopped or the dose was reduced.

The most common grade 3 or 4 drug-related adverse events were increased ALT levels (21%), increased aspartate aminotransferase levels (11%), diarrhea (7%), and increased lipase levels (7%), all of which were reversible upon treatment discontinuation. Sixty-six of 130 patients required at least one dose reduction, and in 8 of 130 patients the study drug was permanently discontinued due to an adverse event. At the 750-mg dose level, 50 of 81 patients required at least one dose reduction, 32 of which occurred in cycle 3 or later. No treatment-related deaths occurred.

Two phase II clinical trials are actively recruiting patients worldwide to further evaluate ceritinib in patients with ALK-positive NSCLC.

Prostate Cancer

Brisk Walking May Lower Prostate Cancer Aggressiveness

Brisk walking helps normalize the shape of vessels in prostate cancer tumors, which may make the tumors less aggressive and more responsive to anticancer therapies, a team of investigators reported at the AACR Prostate Cancer Foundation Conference on Advances in Prostate Cancer Research. Abstract 275791-1

The study’s authors, Erin van Blarigan et al, had demonstrated in a previous study that higher amounts of small, irregularly spaced vessels in human prostate tumors resulted in a greater risk for lethal disease.

They embarked on the current investigation because of other previous data showing that exercise normalized tumor vasculature in mice with prostate cancer; in addition, the authors wrote, brisk walking and vigorous activity have been associated with a lower risk of prostate cancer recurrence and mortality in humans.

In the retrospective study, the team looked at prediagnostic physical activity and vessel morphology in 572 men who underwent radical prostatectomy or transurethral resection of the prostate.

The men were all participants in the Health Professionals Follow-up Study, launched in 1986 to consider the effects of nutritional and lifestyle factors on the incidence of serious illnesses, such as cancer and heart disease. Every 2 years, participants fill out questionnaires that gauge whether they have diseases and what medications they take, as well as their involvement in activities such as smoking and exercise. The men fill out questionnaires about their dietary habits every 4 years.

Before being diagnosed, the men had filled out an average of nearly 5 questionnaires assessing their levels of total, vigorous, and nonvigorous activity, as well as their walking pace. Vessel morphology—including vessel size, regularity of the vessel lumen, and microvessel density&mdash;was assessed through the analysis of tumor-section images stained to detect the expression of the protein CD34. The team of investigators considered the relationship between the cohort’s level of physical activity and their vessel morphology.

They found that prediagnosis brisk walking was associated with more regularly shaped vessels in prostate tumors. Men who walked the fastest, from 3.3 to 4.5 miles per hour, had 8% more regularly shaped vessels than men who walked the most slowly, from 1.5 to 2.5 miles per hour (P = .01). Brisk walking was also associated with larger vessels (P = .06).

Walking pace did not demonstrate any effect on microvessel density, and the amount of time spent walking did not prove meaningful when it came to vessel morphology in general. The authors suggested that further studies should investigate whether increasing brisk walking after prostate cancer diagnosis will fuel positive changes in a man’s tumor vasculature.

Melanoma

Nivolumab Delivers Durable Remissions With Low Toxicity in Advanced Melanoma

Nivolumab, a PD-1-specific antibody, has been shown to produce long-term remissions with limited toxicity in patients with advanced melanoma, according to results from one of the longest follow ups to examine the drug (J Clin Oncol. 2014;32[10]:1020-1030).

In the phase I analysis, the objective response rate (ORR) was 31% for a median duration of 2 years in patients with advanced melanoma. The median overall survival (OS) in nivolumab-treated patients was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively.

“These are striking results for patients with metastatic melanoma,” the study’s senior author F. Stephen Hodi, MD, director of the Melanoma Treatment Center and Center for Immuno-Oncology at Dana-Farber Cancer Institute. “This study provides the first demonstration of the long-term benefits this treatment approach can produce.”

In the study, representing a maximum followup of 4.3 years, patients with previously treated advanced melanoma (n = 107) received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks. Patients treated with nivolumab experienced a median progressionfree survival (PFS) of 3.7 months. PFS rates were 36% and 27% at 1 and 2 years, respectively. In the analysis, the authors pointed out that OS was significantly longer than PFS, and Kaplan-Meier curves for both flattened after 1 year of follow-up.

“The results seen here are remarkable for these patients with treatment-resistant, advanced metastatic melanoma, who had limited life expectancies when they joined the trial,” says study lead-author Suzanne Topalian, MD, professor of surgery and oncology, and director of the melanoma program at Johns Hopkins.

Seventeen patients discontinued therapy for reasons other than disease progression of which 12 (71%) maintained responses off-therapy for at least 16 weeks. The side effects of the treatment were consistent with those observed in other studies of the drug. The most common adverse experiences were fatigue (32%), rash (36%), and diarrhea (18%), most of which occurred in the first 6 months of therapy.

In an extended analysis of 306 patients across various tumor types, the objective response rate and toxicity profiles were similar for patients treated with nivolumab. Moreover, the toxicity profile with nivolumab appears to be in line with the already approved checkpoint inhibitor ipilimumab, Geraldine O’Sullivan Coyne, MD, and colleagues from the National Cancer Institute wrote in an accompanying editorial.

“The continued demonstration of promising clinical outcomes with the use of modern immunotherapy strategies such as nivolumab may allow medical oncologists to have raised expectations for patients with metastatic cancer,” Coyne et al wrote. “Current treatment for metastatic solid tumors, apart from rare exceptions such as testicular cancer, remains palliative, but perhaps immune checkpoint inhibitors can be part of a strategy to enhance the number of patients who can enjoy sustained, durable responses.”

Nivolumab is one of a new generation of drugs that releases the brakes on an immune system attack on cancer. The drug blocks PD-1, a protein on immune system T cells that restrains the cell from leading a charge on the tumor. By interfering with PD-1, nivolumab allows the attack to proceed.

Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on survival in patients with metastatic melanoma. Clinical trials are already under way to assess a combined approach with other immune system-based therapies, such as ipilimumab.

Nivolumab is also being studied as treatment for multiple tumors types, including non-small and small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, hematologic malignancies, triple-negative breast cancer, gastric cancer, and pancreatic cancer.

Nurse Perspective

Rajni Kannan, BS, MS, RN, ANP-BC

Nurse Practitioner

NYU Cancer Institute

NYU Langone Medical CenterNew York, NY

Nivolumab is the newest immunotherapy being studied in metastatic melanoma. In recent years we have seen new novel therapies approved in metastatic melanoma that are changing overall survival in patients who previously had no hope. Immunotherapies such as nivolumab are producing durable responses with minimal toxicities.

It is important for nurses to understand nivolumab’s mechanism of action, for it correlates with the side effect profile and patient’s treatment responses.

Nivolumab is a PD-1 specific antibody. Melanoma cells express PD-L1 on their surface allowing them to prevent detection by the immune system. PD-1 is a protein on the surface of activated T cells. When PD-L1 on melanoma cells attach to PD-1 on T cells, it stops the immune system’s recognition of melanoma cells. This puts the “brakes” on the immune system not allowing for T cells to attack the melanoma cells. Nivolumab, an immune checkpoint inhibitor, works to release the binding of PD-1 to PD-L1 enabling T cells to identify melanoma cells and resume their antitumor activity.

Due to T-cell activation, nivolumab side effects are similar to those seen with ipilimumab. These side effects are immune mediated in nature and are treated with use of systemic corticosteroids for moderate to severe side effects. Early intervention and patient education is the key in management of these immune-mediated side effects. Patients must be educated to report side effects in real time so that prompt interventions can be implemented.

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