Chronic immune-related adverse effects (irAE) arising from adjuvant anti–PD-1 therapy in patients with high-risk melanoma are more common than previously recognized, and often persisted with longer follow-up, according to findings from a multicenter cohort study published in 

Chronic irAEs, which are defined as those that persist after 12 weeks of anti–PD-1 discontinuation, occurred in 43.2% of patients enrolled to the trial (n = 167/387). Although the majority of these chronic irAEs were grades 1 or 2 (96.4%; n = 161/167), most of the effects persisted until last available follow-up (85.6%; n = 143/167).

“It is certainly important to recognize that anti–PD-1 therapy, regardless of this study and others, certainly does improve outcomes for patients with melanoma and is something that I will certainly still be offering my patients” lead study author Douglas Johnson, MD, MSCI, an associate professor of Medicine at Vanderbilt University Medical Center, and clinical director of Melanoma at Vanderbilt-Ingram Cancer Center, told 

. “There is a subset of patients with stage III melanoma who have a very low risk of recurrence, and for those patients, [these data] may make us reevaluate how to [treat] them, and perhaps [revisit] how [we] make risk/benefit determinations in those settings.”

Moreover, irAEs such as endocrinopathies (83.0%; n = 73/88), arthritis (48.9%; n = 22/45), xerostomia (52.9%; n = 9/17), neurotoxicities (73.3%; n = 11/15) and ocular effects (62.5%; n = 5/8), were the most likely to become chronic, while effects impacting visceral organs like the liver, colon, lungs, and kidneys, had much lower rates of becoming chronic.

“We tend to think of specific organs that are being affected by these toxicities,” Johnson said. “The big ones that come to mind are the colon, the lungs, and the liver, but the toxicities in those organs seem to really get better; it was toxicities in the smaller organs that seemed to more commonly develop into chronic [effects].”

Adjuvant therapy with anti–PD-1 agents has been found to result in improved relapse-free survival (RFS) in patients with resected, advanced-stage melanoma. However, the long-term effects of this treatment approach remain uncharacterized. To address this knowledge gap, investigators launched this retrospective, multicenter cohort study to determine the incidence, length, spectrum and associations of chronic irAEs that arise from adjuvant anti–PD-1 treatment in patients with stage III and IV melanoma. The study was conducted from 2015 to 2020 at 8 medical centers across the United States and Australia.

The median age for patients enrolled on the study was 63 years (range, 17-88) and the majority were male (60.7%; n = 235/387). Additionally, 74.9% (n = 290) had preexisting comorbidities, 85.8% (n = 332) had cutaneous primary sites, and 51.2% (n = 198) had 

 wild-type variants. Moreover, 33.1% (n = 128) of patients had resected stage IIIB melanoma, while 39.5% (n = 153) had resected stage IIIC disease. Around 84% (n = 326) of patients had received prior treatment with nivolumab (Opdivo), and 15.8% (n = 61) of patients received pembrolizumab (Keytruda), with a median treatment duration of 306 days (range, 1-1049).

Reasons for treatment discontinuation included therapy completion for 50% (n = 193), irAEs for 25.3% (n = 98) of patients, and disease progression for 20.9% (n = 81) of patients. Moreover, median RFS and overall survival had not been reached. At a median follow-up of 529 days, the majority of patients (93%) were alive. Notably, patients with observed acute and chronic irAEs were found to have superior RFS compared with those who did not experience irAEs.

Of all 387 patients included on the trial, 69.0% (n = 279) experienced acute irAEs; 44.2% (n = 171) of these effects were grade 2 or higher, while 13.4% (n = 52) were grades 3 to 5 in severity. Two patients died from irAEs; 1 patient had myocarditis, while the other had Guillain-Barré–like syndrome.

The most common acute irAEs observed were dermatitis/pruritus (25.8%), thyroiditis/hypothyroid (16.3%), arthralgias (10.6%), colitis/diarrhea (9.8%), hepatitis (6.2%), pneumonitis (4.4%), and xerostomia (4.1%). About 28% of patients required treatment with glucocorticoids; 55.0% needed this for grade 2 irAEs, while 45.0% needed them for grade 3 to 5 effects.

In those who developed chronic irAEs, systemic glucocorticoids were needed in 32.9% (n = 55) of patients. The most common chronic irAEs observed were hypothyroidism (14.0%), arthralgias (5.7%), dermatitis/ pruritus (6.6%), adrenal insufficiency (3.1%), and xerostomia (2.3%).

Age and gender were not found to be linked with the development of chronic irAEs (63.0 years vs 63.0 years in those who did not develop chronic irAEs, 

 = .31, respectively). Moreover, the median time of onset of acute irAEs was not determined to be associated with chronicity (

 = .95). With the exception of endocrinopathies, those who were given glucocorticoids for acute effects did not go on to develop chronic effects more often than those who did not receive the agents (

The investigators concluded that the risks of chronic irAEs should be integrated into treatment decision-making for this patient population.

“In terms of future directions, we might potentially be able to intervene early and identify these effects before they established themselves to become chronic,” Johnson noted.

Patrinely JR, Johnson R, Lawless AR, et al. Chronic immune-related adverse events following adjuvant anti–PD-1 therapy for high-risk resected melanoma. 

. Published online March 25, 2021. doi:10.1001/jamaoncol.2021.0051

Articles

Chronic immune-related adverse effects arising from adjuvant anti–PD-1 therapy in patients with high-risk melanoma are more common than previously recognized, and often persisted with longer follow-up.

Chronic Immune-Related Adverse Events Are Common in Certain Melanoma Subgroups

Provider communication is extremely important, especially when dealing with a pediatric cancer diagnosis. In this episode of “The Vitals,” Bryan A. Sisk, MD, MSCI, assistant professor of pediatric hematology and oncology at the Washington University School of Medicine discusses his recent research on communication barriers between healthcare providers and children with cancer and their families.

While some of these issues can be found in the broader cancer space, others – like how much information to give a 6-year-old versus a 16-year-old – align more with the intricacies of pediatrics. Sisk talks about this, and the improvements he hopes to see in this space in years to come.

Podcasts

A Chat on Communication Barriers in Childhood Cancer

The FDA approved nivolumab (Opdivo) plus certain types of chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma. This is the first frontline immunotherapy regimen approved for gastric cancer.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in 

The approval was based on a randomized, multicenter, open-label trial that included 1,581 treatment-naïve patients with advanced or metastatic gastric cancer, GEJ cancer, and esophageal adenocarcinoma – 789 of whom received nivolumab plus chemotherapy.

Those in the nivolumab/chemotherapy arm had longer average survival than those who were given chemotherapy alone, 13.8 months and 11.6 months, respectively.

Most common adverse events from nivolumab – a monoclonal antibody that enhances T-cell function to fight cancer – were peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation and musculoskeletal pain.

Nurses should also look out for immune-related adverse events, which could be serious. They include: pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Patients and providers must communicate if the patient has any issues with their immune system, lung or breathing problems, liver problems, have had an organ transplant, or are pregnant/plan to become pregnant.

“The FDA is committed to bringing new safe and effective treatment options like Opdivo to patients with advanced cancer,” Pazdur said.

The FDA approved nivolumab (Opdivo) plus certain types of chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma.

FDA Approves Frontline Nivolumab for Gastric Cancers

Research shows that individuals with low socioeconomic status, as well as members of racial/ethnic minority populations, often face disparities in cancer care. Considering that about one-quarter of the Latino population lives in poverty, and that this is the largest ethnic minority group in the United States,

 improving oncology care for this demographic should be a priority.

Cancer-related disparities for Latino populations include diagnosis at more advanced disease stages, delays in treatment initiation, and psychosocial morbidities such as poorer quality of life compared with non-Latino White individuals.

 In addition, poverty-exposed children with cancer suffer from poorer cancer-related outcomes, including lower survival rates and earlier relapse.

 Cancer health disparities extend to caregivers as well, including increased stress and negative health among Latino caregivers of family members with cancer.

 Moreover, health care providers tend to underestimate the needs of Latino parents of children with cancer, assuming that Latino families want less information about a child’s cancer diagnosis and prognosis than is actually wanted.

 Therefore, understanding and ameliorating factors contributing to disparities in health outcomes in Latino children and adults with cancer as well as their caregivers is vital to minimizing disparities in morbidity and mortality.

It has been proposed that access to health care is a critical avenue to eliminating racial and ethnic health disparities because it reflects a societal, rather than individual, effort to address broader systemic issues that contribute to such disparities with a focus on provision and cost support of health care. Enacting change in health care access is a task for nurses engaged in clinical care, research, and policy.


A potentially valuable framework for this work divides the approach into 3 phases: detection, understanding, and reduction of health-related disparities. Much of the work in this field has focused on detection; that is, identifying certain groups as receiving poorer quality of care, lacking access to care, and having poorer health outcomes. The second phase, understanding, relates to identifying potential determinants of health disparities that will ideally inform interventions or efforts to eliminate disparities. Understanding is often limited by a narrow scope that fails to consider the interplay of the broad range of individual, family, community, societal, and systemic factors that contribute to health-related disparities. The final phase, reduction, involves developing and implementing interventions aimed at reducing and eliminating disparities that unfortunately are least representative of the literature on health disparities.

Clinically, application of this framework may be accomplished by broadening assessment of potential determinants of health to under- stand the complex range of factors that may contribute to potential disparities among the patients we serve. For example, more detailed assessment of social determinants of health (eg, food, housing, energy, and transportation insecurity) may reveal opportunities to address barriers to care. Cross-sector collaborations, such as partnering with digital transportation companies like Uber or Lyft, can help address barriers. Nurse scientists can also take the lead in developing research programs that address and reduce health disparities. 

Engaging with the target community allows for development of sustainable and culturally relevant interventions. Such approaches, including community-based participatory research, establish a collaborative partnership that engages community experts in decision-making and changes in the practice of health care. Academic-community research collaborations can successfully reduce health disparities and, more specifically, have been shown to address systemic inequities, such as those related to education, financial insecurity, health literacy, and access to technology.

Advances in detection and treatment of cancer have led to increases in survival rates in recent decades. Unfortunately, for some populations, these advances have not affected cancer-related morbidity and mortality. Thus, it is crucial that nurse clinicians and scientists adopt a wide lens of assessment and intervention using a population health approach to incorporate myriad factors that contribute to these health inequities. Reduction and elimination of health disparities stems from detection and understanding, and nurses have a key role in clinical settings, research partnerships with communities impacted by disparities, and in policy decisions and implementation. Community and cross-sector partnerships can allow for innovative approaches that address social determinants of health not just at the individual but at the larger community and population levels and can lead to improvements in cancer- related outcomes for all patients and families.

1. Stepler R, Brown A. 2014, Hispanics in the United States statistical portrait. Pew Research Center. April 19, 2016. https://www.pewresearch.org/hispanic/2016/04/19/2014-statistical-information-on-hispanics-in-united-states/

2. Cancer Facts & Figures for Hispanics/Latinos 2018-2020. American Cancer Society. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-hispanics-and-latinos/cancer-facts-and-figures-for-hispanics-and-latinos-2018-2020.pdf

3. Luckett T, Goldstein D, Butow PN, et al. Psychological morbidity and quality of life of ethnic minority patients with cancer: a systematic review and meta-analysis. 

. 2011;12(13):1240-1248. doi:10.1016/S1470-2045(11)70212-1

4. Wahi A, Phelan M, Sherman-Bien S, Sender LS, Fortier MA. The impact of ethnicity, language, and anxiety on quality of life in children with cancer. 

. 2016;11(3):817-836. doi:10.1007/s11482-015-9399-6

5. Bona K, Blonquist TM, Neuberg DS, Silverman LB, Wolfe J. Impact of socioeconomic status on timing of relapse and overall survival for children treated on Dana-Farber Cancer Institute ALL Consortium Protocols (2000-2010). 

. 2016;63(6):1012-1018. doi:10.1002/pbc.25928

6. Crist JD, García-Smith D, Phillips LR. Accommodating the stranger en casa: how Mexican American elders and caregivers decide to use formal care. 

2006;20(2):109-126. doi:10.1891/rtnp.20.2.109

7. Israel B, Eng E, Schulz A, Parker EA. Introduction to methods in CBPR for health. In: Israel BA, Eng E, Schulz AJ, Parker EA, eds. 

Methods for Community-Based Participatory Research for Health

April is National Minority Health Month, highlighting the need for health care and community sectors to come together and improve cancer outcomes for underserved populations.

Approach Health Disparities From All Angles

Receiving a diagnosis of either cancer or diabetes can be life changing, but for patients with both diseases, it can prove especially challenging. Research shows that 8% to 18% of individuals living with cancer also have diabetes

 and that treating both simultaneously makes the process more complicated for nurses and their patients. The American Diabetes Association states, “Cancer and diabetes are diagnosed within the same individual more frequently than would be expected by chance.”

“As our population ages and people are living longer, we can expect to see the number of patients receiving diagnoses of both cancer and diabetes increase,” said Jill Olausson, PhD, RN, CDE, an assistant professor and assistant chair, Master’s of Nursing in Healthcare Administration, at Azusa Pacific University in California. Olausson is part of the Glycemic Control for Patients with Cancer Nursing Task Force, a group of nurses committed with improving health-related outcomes and the care of oncology patients with diabetes.


People with diabetes (primarily type 2) are at a higher risk of developing certain cancers than those without diabetes, as the diseases share risk factors such as aging, obesity, poor nutrition, and physical inactivity.

 Olausson notes that predni- sone and other steroids used to treat or prevent nausea, or as a component of cancer treatment, can also cause a spike in blood sugars and compound the management of diabetes. Patients who receive steroids should be closely monitored with premeal glucose testing and additional testing 2 hours after a meal.

Caring for Patients With Diabetes and Cancer


“Cancer patients with diabetes are at an increased risk for developing infections, being hospitalized, and requiring chemotherapy reductions or stoppages,” says Denise Hershey, PhD, RN, FNPBC, an associate professor at Michigan State University’s College of Nursing in East Lansing. Unfortunately, Hershey says there is not sufficient evidence on the best way to manage diabetes in patients with cancer. She believes in looking at each patient’s overall health rather than focusing solely on their cancer.

“It’s important for oncology nurses to work with diabetes educators, nutritionists, and others to form a comprehensive care plan for patients,” Hershey says. “Nurses can assess how well a patient’s diabetes is being controlled by looking at the patient’s A1C [glycated hemoglobin] at the time of their initial cancer diagnosis and seeing if they now appear to [have] hyperglycemia.”

Care plans can help patients balance their glucose levels with their cancer treatment after discharge. “It’s important to look at barriers patients may be facing, such as not being able to afford the high cost of diabetic test strips,” Hershey says. “Rather than just advising them to exercise, letting them know that regular exercise can help stabilize blood sugar levels while also lowering the chances of cancer adverse events [AEs] such as fatigue and neuropathy.”

Recent research shows that blood glucose above 180 increases the risk of complications in hospitalized patients.

 Hershey says oncology patients sometimes make the mistake of prioritizing their cancer diagnosis over their diabetes.

“We know glycemic control plays a role in the overall health quality of life for oncology patients, level of symptom severity, and can also affect overall survival,” Hershey says. “Educating patients about how to self-manage their glycemic control is just as important as treating their cancer, in order to achieve the best outcomes.”

Oncology nurses also need to be aware of changes in a patient’s condition; many
cancer symptoms are also signs of diabetes. Uncontrolled high blood sugar can lead to dehydration, but extreme thirst can also be an AE of chemotherapy. Both diabetes and cancer complications can cause or worsen neuropathy. “We need to look at cancer survivorship and ensure these patients receive optimal diabetes care and achieve their glycemic targets,” Hershey says.

Nurses need to know these key concepts when treating patients who have diagnoses of both cancer and diabetes.

Dual Diagnosis: Nurses Face Challenges in Caring for Patients With Both Cancer and Diabetes

Caregivers have their own set of issues and anxieties, but a telehealth support service may help. 

Telehealth Program Supports Family Caregivers of Patients With Brain Cancer

Two tests for homologous recombination deficiency have been FDA approved for patients with ovarian cancer, including myChoice CDx and FoundationOne CDx, and they produce important information that can be used to guide treatment decisions.

HRD Testing Expands, But Still Lacks Standardization in Ovarian Cancer

 is the leading national organization providing free, professional support services and information to help people manage the emotional, practical and financial challenges of cancer. Our comprehensive services include counseling and support groups over the phone, online and in-person, educational workshops, publications and financial and co-payment assistance. All Cancer

 services are provided by oncology social workers and world-leading cancer experts.

The information provided by the assessment is essential as it contributes to shared decision making. The goal of shared decision-making is for patients and clinicians to partner together and make informed choices based on the patient’s needs, values and preferences.

Comprehensive Assessment Is Key for Geriatric Patients

A breast surgeon discusses the best practices for breast cancer surgery during the COVID-19 pandemic.

Breast Cancer Surgery in a Pandemic: What's the Best Approach?

The FDA granted a regular approval to sacituzumab govitecan (Trodelvy) for previously treated patients with unresectable locally advanced or metastatic triple-negative breast cancer.

FDA Approves Sacituzumab Govitecan for Pretreated, Metastatic TNBC

Wearable fitness trackers may boost fitness, quality of life and overall health in childhood cancer survivors.

Wearable Fitness Trackers May Improve Health in Childhood Cancer Survivors

The FDA has approved a new biweekly dosing regimen of 500 mg/m2 as a 120-minute intravenous infusion for cetuximab (Erbitux) for patients with KRAS wild-type, EGFR-expressing colorectal cancer or squamous cell carcinoma of the head and neck.

FDA Approves Additional Cetuximab Dose for KRAS Wild-Type, EGFR-Expressing CRC, Head and Neck Cancer

Patient-reported outcomes (PRO) hold valuable information on how patients are handling cancer treatment. Recent research analyzed which methods of PROs patients prefer. 

Study Examines Patient Preference in Patient-Reported Outcome Tracking

Wade T. Iams, MD, discusses the efficacy and safety of lurbinectedin in patients with small cell lung cancer, the impact of its approval on the paradigm, and remaining questions regarding its use.

Lurbinectedin Shows Promise in Small Cell Lung Cancer Treatment

Optimizing first- and second-line therapy, understanding the role of maintenance therapy for patients with BRCA-positive disease, and developing improved therapeutic options for elderly patients has become a priority for research in metastatic pancreatic cancer.

Top Medical News

Chronic Immune-Related Adverse Events Are Common in Certain Melanoma Subgroups

A Chat on Communication Barriers in Childhood Cancer

FDA Approves Frontline Nivolumab for Gastric Cancers

Approach Health Disparities From All Angles

Dual Diagnosis: Nurses Face Challenges in Caring for Patients With Both Cancer and Diabetes

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