Alana Hippensteele, Editor

A phase 3 trial investigating the PD-1 inhibitor cemiplimab (Libtayo, Regeneron) in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy showed a significant improvement in overall survival (OS), with a reduction in the risk of death by 31% compared to chemotherapy in the overall population, according to a presentation at the European Society for Medical Oncology Virtual Plenary.

These positive results add to the previously reported data showing an improvement in OS with cemiplimab compared to chemotherapy. In light of these positive findings, the data from this trial will be used as the basis for regulatory submissions in 2021.

"Improvements in progression-free survival [PFS] and objective response rate [ORR] were also demonstrated in the overall population compared to chemotherapy. Taken together, this landmark trial—which enrolled patients regardless of PD-L1 expression status—helps support the use of [cemiplimab] as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options," said trial investigator Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine, in a press release.

Currently, cervical cancer is the fourth leading cause of cancer mortality in women globally, with the most frequently diagnosed age group being women aged 35 to 44 years. Every year, approximately 570,000 women are diagnosed with cervical cancer, with deaths among those diagnosed totaling more than 250,000 annually. In the United States alone, there are approximately 14,500 patients diagnosed annually, with approximately 4000 women dying from the disease each year.

Although human papillomavirus infection is the cause of a majority of cases, approximately 80% are also classified as squamous cell carcinoma (SCC), which occurs from within cells in the lining at the bottom of the cervix. The remaining 20% of cases are classified as adenocarcinomas, which arises from glandular cells in the upper cervix. When detected early, cervical cancer is generally curable and can be managed; however, in advanced stages, the treatment options available become limited.

In the overall patient population, the investigators found that OS, PFS, and ORR significantly improved for those treated with cemiplimab (n=304), compared to chemotherapy (n=304). Specifically, the investigators observed a 31% reduction in mortality risk (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.56-0.84; one-sided p=0.00011), a 25% reduction in disease progression risk (HR: 0.75; 95% CI: 0.63-0.89; one-sided p=0.00048), and 16% ORR (50 patients; 95% CI: 13-21%; one-sided p=0.00004), compared to 6% with chemotherapy (19 patients).

Among this population, the median duration of response was 16 months with cemiplimab (95% CI: 12 months to not yet evaluable) and 7 months with chemotherapy (95% CI: 5-8 months), per Kaplan-Meier estimates.

Seventy-eight percent of trial participants were found to have advanced cervical cancer classified as SCC and also went on to experience significant improvements following treatment with cemiplimab (n=239) versus chemotherapy (n=238).

Specifically, patients in this population experienced a 27% reduction in mortality risk (HR: 0.73; 95% CI: 0.58-0.91; one-sided p=0.00306), a 29% reduction in disease progression risk (HR: 0.71; 95% CI: 0.58-0.86; one-sided p=0.00026), and 18% ORR (42 patients; 95% CI: 13-23%) compared to 7% with chemotherapy (16 patients; 95% CI: 4-11%).

Although the investigators did not set the assessment of adenocarcinoma as a pre-specified endpoint, a post-hoc analysis demonstrated that patients treated with cemiplimab (n=65) compared to chemotherapy (n=66) experienced a 44% reduction in mortality risk (HR: 0.56; 95% CI: 0.36-0.85; nominal one-sided p<0.005), a 9% reduction in disease progression risk (HR: 0.91; 95% CI: 0.62-1.34), and 12% ORR (8 patients; 95% CI: 6-23%), compared to 5% with chemotherapy (3 patients; 95% CI: 1-13%).

Additionally, the phase 3 trial demonstrated that patients treated with cemiplimab experienced an improvement or maintenance of their baseline Global Health Status/Quality of Life (GHS/QOL) over time. However, patients treated with chemotherapy experienced a deterioration that was clinically significant by cycle 8, per the European Organisation for Research and Treatment of Cancer QLQ-C30 (overall estimated mean change [95% CI]: improvement of 1.01 [-2.033, 4.047] for Libtayo, worsening of -6.81 [-10.977, -2.637] for chemotherapy; difference: 7.81; one-sided nominal p=0.00040).

The investigators observed no safety signals for patients treated with cemiplimab. The investigators had assessed safety in patients who received at least 1 dose of study treatment, which included 300 patients in the cemiplimab group (median duration of exposure: 15 weeks; range: 1-101 weeks) and 290 patients in the chemotherapy group (median duration of exposure: 10 weeks; range: 1-82 weeks).

In terms of adverse events (AEs) observed during the trial, investigators found 88% of cemiplimab patients and 91% of chemotherapy patients experienced AEs. In 15% or more of cemiplimab patients, AEs included anemia (25% cemiplimab, 45% chemotherapy), nausea (18% cemiplimab, 33% chemotherapy), fatigue (17% cemiplimab, 16% chemotherapy), vomiting (16% cemiplimab, 23% chemotherapy), decreased appetite (15% cemiplimab, 16% chemotherapy), and constipation (15% cemiplimab, 20% chemotherapy).

Additionally, grade 3 or higher AEs were observed in 45% of cemiplimab patients and 53% of chemotherapy patients, whereas in 15% or more of patients, certain grade 3 or higher AEs were observed more frequently in the cemiplimab group. These AEs included asthenia (2% cemiplimab, 1% chemotherapy) and pyrexia (less than 1% cemiplimab, 0% chemotherapy).

The investigators also observed immune-related AEs in 16% of cemiplimab patients and fewer than 1% of chemotherapy patients. The AEs at grade 3 or higher occurred in 6% of cemiplimab patients and fewer than 1% of chemotherapy patients. However, patients discontinuing treatment due to AEs only occurred among 8% of cemiplimab patients and 5% of chemotherapy patients.

Positive Phase 3 Libtayo® (cemiplimab) Results in Advanced Cervical Cancer Presented at ESMO Virtual Plenary. Tarrytown, NY: Regeneron Pharmaceuticals; May 12, 2021. 

https://investor.regeneron.com/news-releases/news-release-details/positive-phase-3-libtayor-cemiplimab-results-advanced-cervical

Articles

A phase 3 trial investigating the PD-1 inhibitor cemiplimab in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy showed a significant improvement in overall survival.

Positive Results for the Treatment of Advanced Cervical Cancer 

There are widespread mental health concerns among children and teens currently, with 1 in 4 to 5 having a mental health problem, said Bernadette Melnyk, PhD, RN, CPNP, PMHNP, FAAN, during a session at the National Association of Pediatric Nurse Practitioners Virtual Conference 2021. The most commonly occurring mental health disorders in this population are anxiety, depression, and ADHD.

However, it is estimated that less than 50% of children and teens with a mental health disorder receive any treatment. This is of particular concern considering suicide remains the second leading cause of death in people aged 10 to 34 years in the United States.

“If every clinician, advanced practice provider, and physician could get great at providing evidence-based screening and intervention for just anxiety and depression in children, teens, and young adults, we could really put a dent in these mental health problems,” Melnyk said during the session.

Furthermore, during the struggles many have endured during the COVID-19 pandemic, there is an additional mental health epidemic that has emerged within the pandemic, Melnyk explained. The CDC and the Morbidity and Mortality Weekly Report released data showing 25% of Americans aged 18 to 25 years have thought about suicide since the start of the pandemic, highlighting the critical need for mental health promotion and development of resiliency skills so that a paradigm shift can occur around this issue.

“Because so many people are suffering from depression and anxiety related to the COVID-19 pandemic, we are seeing a rise in substance use, unhealthy eating, and a decline in physical activity. If we do not address these mental health problems urgently now, we are also going to see downstream affects in chronic disease in 3 to 5 years from now,” Melnyk said during the session.

There are a variety of risk factors for mental health disorders in children and teens. Poor self-esteem is a significant predictor, although it is often not screened for by providers. For this reason, every contact with a patient should be seen as a potential opportunity to screen for mental health disorders, especially during the pandemic, according to Melnyk. Asking a single screening question during a session such as, “On a scale from 0 to 10, how good do you feel about who you are?” can be an effective tool for assessing patient risk.

There are other valuable screening tools providers can use as well, such as the Pediatric Symptom Checklist, which has been found to be a valid and reliable first screen, as it is a short form with 17 items that takes approximately 5 minutes to complete.

For assessing risk for depression and anxiety disorders, the PHQ-9, GAD-7 and SCARED screening tools are also valuable. Additionally, the CRAFFT screen is used for assessing substance use risk, while the ACE screen helps to assess adverse childhood experiences.

If the results of the screening tool demonstrate further investigation is needed, a clinical interview should then be conducted with further evaluation completed by a health care provider.

“But we have to remember that screening is not diagnosis alone. Screening just raises a red flag that requires a good comprehensive interview and evaluation by the health care provider,” Melnyk said during the session.

Melnyk highlighted a strong outline that is available for the integration of behavioral health into primary care using the Screening, Brief Intervention and Referral to Treatment (SBIRT) model. SBIRT details that the starting point should be a screening for a mental health disorder in the primary care setting, which is then followed by a brief intervention that can be provided in the primary care location.

If necessary, a referral to a mental health provider or a consultation service can proceed this, with subsequent treatment offered by the primary care provider, integrated psychologist, mental health provider, or specialty care based on the needs of the patient.

“I like to add another letter to SBIRT, and that is H for Hope. I never let a child, teen, or young adult leave me without instilling hope that there are fabulous, evidence-based treatments to help them,” Melnyk said.

In the primary care setting, the 2 most common mental health disorders that providers observe are anxiety disorders and depressive disorders. However, there are now a rising number of trauma, stress-related, and obsessive compulsive disorders emerging.

“But again, if we could just get really good at delivering cognitive-behavioral-health based interventions for children and teens with depression and anxiety, we would avoid long wait times to mental health providers,” Melnyk said during the session. “Unfortunately, a lot of people feel that if you’re not born with resilience, you can’t develop it, and that couldn’t be further from the truth. All throughout life, you can build resiliency skills and cognitive behavioral skills that are wonderfully protective factors against mental health disorders.”

Melnyk B, Lusk P. Evidence-based Screening and Mental Health Interventions for Primary Care. Presented at: National Association of Pediatric Nurse Practitioners Virtual Conference 2021; March 27, 2021; virtual. 

https://napnap21.org/community/#/session-stream/42207

There are widespread mental health concerns among children and teens currently, with 1 in 4 to 5 having a mental health problem.

Evidence-based Screening for Mental Health Disorders in Children, Teens is Critical During Pandemic

With 1 in 4 children in the United States living in an immigrant family, the health care needs of this pediatric population are a critical area of focus when addressing health disparities for children, said Albrey Love DNP, APRN, PNP-PC, during a session at the National Association of Pediatric Nurse Practitioners Virtual Conference 2021.

For the purposes of understanding exactly what qualifies as a child living in an immigrant family, Love explained that this population is defined as children who are foreign born or are born in the United States who live with at least 1 foreign-born parent.

Currently, a significant portion (64%) of children living in an immigrant family reside in 6 states: California, Texas, New York, Florida, Illinois, and New Jersey. However, from 1990 to 2019, the largest growth in this population occurred elsewhere, in states such as North Carolina, Nevada, Georgia, and Arkansas.

The reason children migrated to this country vary widely, but some reasons can be quite complex, Love explained.

“Children migrate to this country with or without their parents for a number of reasons,” Love said during the session. “Some of the most common that you might be the most familiar with are economic needs, possibly educational pursuits, but some may also be a victim of human trafficking or are escaping a country due to violence.”

The immigration status in this population can also be highly variable, with some children entering on a temporary visa, a tourist visa, or on a lawful permanent residence visa. Some also qualify for the Deferred Action for Childhood Arrivals (DACA) program, which defers deportation of certain people who came to the United States as children and meet several guidelines. DACA allows these individuals to request consideration of deferred action for a period of 2 years, with the ability to renew.

“DACA allows young adults who had arrived in the United States as children without legal status but grew up here to essentially apply for deportation relief and working visas,” Love said during the session.

Children living in an immigrant family are also approximately twice as likely as other children in the United States to not be covered by health insurance. Love explained that sometimes this lack of insurance is due to the services not being available, whereas other instances may be due to a lack of knowledge regarding the programs that exist that could provide them with health insurance coverage.

This pediatric population is also more likely to live below the poverty level, with access barriers to programs and benefits causing such problems to persist. Love noted that additionally, for these children, the threat of deportation or forced separations from their families are very real.

“The family immigration status represents an important and often neglected social determinant of health in this family,” Love said. “The immigration status affects their access to care and intertwines with other social determinants of health.”

Love explained that these social determinants of health can include poverty, food insecurity, health literacy, educational disparities, or discrimination, the latter of which they may experience based on their family’s immigration status.

In order to assess the mental, emotional, and behavioral health of immigrant children in light of the varying factors at play in their health and wellness, there are several screenings that can be used to help assess their wellbeing.

“Screening for trauma is very important in these children,” Love said during the session. “It’s really easy for us to kind of think of their journey as just hopping on a plane and crossing into the country. However, depending on their country of origin, it can be quite traumatic or it could be seamless. It really just depends on the country they’re coming from and the reason migration is happening.”

Upon arrival to the United States, immigrant children may actually also be healthier than native-born children, which is termed the “immigrant paradox” or “healthy immigrant effect” in the literature, according to Love. This is important to recognize as these children may require longer term care in order to develop a rapport with their provider, at which point signs of trauma may begin to appear.

“That’s why this ongoing screening is recommended,” Love said. “Trauma can occur before the migration journey, during the journey, on arrival, or post migration.”

There are also various types of trauma that could have occurred previously or are occurring, such as physical or sexual abuse, witnessing interpersonal violence, human trafficking, actual or threatened separation from parents, or exposure to armed conflicts.

Yet, immigrant families also bring strengths to the United States that may be less common in native-born families, which can be assessed using the Strengths and Difficulties Questionnaire. Love explained that a significant majority of immigrant families arrive intact, with multiple generations living in the same household. This can be a strength that can help build resilience in this pediatric population.

“Typically, what we see is that children in these families are not growing up in disjointed family units,” Love said during the session. “That’s an actual strength of these families and provides resilience for them, unlike children in the United States who are non-immigrants who are affected by divorce more commonly. These families are typically intact.”

Love A, Whited T. Nursing Beyond the Borders: Addressing Healthcare Needs and Health Disparities for Children in Immigrant Families. Presented at: National Association of Pediatric Nurse Practitioners Virtual Conference 2021; March 26, 2021; virtual. 

https://napnap21.org/community/#/session-stream/42189

With 1 in 4 children in the United States living in an immigrant family, the health care needs of this pediatric population are a critical area of focus when addressing health disparities for children.

The Importance of Screening for Both Trauma and the Strengths of Children Living in an Immigrant Family

During the coronavirus disease 2019 (COVID-19) pandemic, many patients in the United States reduced the number of in-person preventive and elective health care visits and increased the number of telemedicine appointments. However, an analysis of the data from March and April 2020, which were the first 2 months of the COVID-19 pandemic lockdown, found that the switch to telemedicine was not sufficient enough to offset the overall reduction in visits.

The analysis of the data was pulled from the medical records of approximately 5 million Americans with private health insurance and demonstrated that the number of mammograms and colonoscopies decreased by approximately 65%, as these types of elective medical care were not easily transferable to a telemedicine format. Overall, use of preventive and elective health care by patients declined by 23% in March and by 52% in April.

However, in lower-income or predominately non-white zip codes, there was a lower reduction in in-person care in addition to lower rates of telemedicine use. The authors who published these findings in 

 noted that this is another example of how the COVID-19 pandemic intensified existing disparities related to health care.

"This adds detailed evidence to the anecdotal reports that Americans quit going to see the doctor when the pandemic shutdown started," said lead author Christopher Whaley, PhD, a policy researcher at the nonprofit research organization RAND Corporation, in a press release. "If important visits are only delayed for a few months, there will likely be no harm. But if patients do not get important screenings, there could be long-term negative health consequences."

Although other studies have analyzed data from this same period, most have assessed data from a single health system or geographic market in order to observe the impact of COVID-19 on the utilization of medical services. In this study conducted by Whaley and his colleagues, the researchers used insurance claims data from 2018 to 2020 from approximately 200 employers across the country.

The results of the study demonstrated that when compared to the rates in March and April 2019, colonoscopies decreased by approximately 70% during March and April 2020. When conducting the same comparison for mammograms, the researchers observed a 67% decrease among women aged 46 to 64 years.

Additionally, utilization of blood sugar tests decreased by approximately 50%, vaccinations among children under age 2 decreased by 22%, and angioplasty procedures decreased by approximately 17%. Surgeries such as musculoskeletal surgery and cataract surgery, as well as MRIs, all decreased by 45% or more. However, only a small decreased was observed in utilization of chemotherapy treatments.

In April 2020, use of telemedicine appointments increased by over 4000% when compared to April 2019. Yet, this significant increase in telemedicine visits replaced only approximately 40% of the decline in in-person visits during this period.

Notably, the authors observed that patients living in lower-income or predominately non-white zip codes had approximately a third lower increase in telehealth visits than those who lived in the wealthiest neighborhoods.

"The extent to which access barriers to telemedicine contribute to lower rates of in-person care deferral, and thus increases in potential exposure to COVID-19, should be examined in future work," Whaley said in the press release.

Health care use drops during pandemic; switch to telemedicine creates disparities. Rand Corporation; November 5, 2020. 

https://www.eurekalert.org/pub_releases/2020-11/rc-hcu110320.php

During the first 2 months of the COVID-19 pandemic, many Americans reduced their in-person preventive and elective health care visits and increased telemedicine appointments. 

Telemedicine Use During the First 2 Months of the Pandemic Did Not Offset the Drop in In-Person Visits

In a recent study conducted in Sweden, researchers found that women who were diagnosed with invasive cervical cancer had an increased risk of iatrogenic injuries, which are injuries that occur as a result of medical intervention, and noniatrogenic injuries, which occur due to accidents and self-harm.

The correlation was observed through the analysis of data from approximately 3 million women who had participated in cervical cancer screenings during the period of 2001 to 2012. By cross referencing multiple Swedish registries, the researchers were able to identify women within this cohort who received a diagnosis of invasive cervical cancer or cervical cancer precursor lesions, as well as women who had a normal smear during follow-up examination.

"Cervical cancer screening is one of the most successful cancer prevention programs, [and] has greatly reduced cervical cancer incidence and mortality," said Qing Shen, PhD, researcher in the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm, in a prepared statement. "Despite these substantial benefits, our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic workup, although at a very low level."

In prior research, Shen and her colleagues had found the potential for increased risk of injuries to be demonstrated during the time period before and after a diagnosis of any cancer.

"These injuries were likely a result of invasive procedures and the severe psychological distress experienced during the clinical evaluation of a potential cancer," Shen said in the press release. She additionally noted that what remains unknown is whether there would be a similar increase in risk among patients screened for cervical cancer if an organized cancer screening program was largely accessible.

After analysis of the initial 3 million women who had participated in cervical cancer screenings, the final cohort of women included in the study were approximately 1.85 million women with a normal smear, approximately 22,000 women with cervical intraepithelial neoplasia (CIN) grade 1, approximately 21,000 women with CIN grade 2 (CIN2), approximately 37,000 with CIN grade 3 (CIN3)/adenocarcinoma in situ (AIS), and approximately 5000 women with invasive cervical cancer.

The researchers then investigated the incidence rates of both iatrogenic injuries and noniatrogenic injuries that had occurred during the diagnostic workup. They found that the Iatrogenic injuries were frequently related to receipt of a punch biopsy, while noniatrogenic injuries were most frequently the result of unintentional falls.

For those injuries that occurred during the diagnostic workup, incidence rate ratios were found through comparing women with a diagnosis of cervical cancer or its precursor lesions to women who had a normal smear, with adjustments made for age, calendar period, screening adherence, education, income, and marital status.

The results of the research showed that women with a diagnosis of invasive cervical cancer, when compared with women with a normal smear, had 8 times the likelihood of iatrogenic injuries, while women with CIN3/AIS had a 3 times increased likelihood of iatrogenic injuries. However, women with CIN1-2 did not have a significantly increased rate of iatrogenic injuries when compared with women with a normal smear.

"Women with invasive cancer can have greater vascularity due to tumor growth, which can lead to hemorrhage and hematoma following a biopsy," Shen said.

Additionally, the results showed that women with a diagnosis of invasive cervical cancer had about twice the likelihood of noniatrogenic injuries than women with a normal smear. However, women with CIN1-2, CIN3, or AIS did not have a significantly increased rate of noniatrogenic injuries when compared with women with a normal smear.

"This study, for the first time, systematically examined the risks of injuries during the cervical diagnostic workup,” Shen said. “Although the chance of having such injuries was rare, we found an increased risk of inpatient care for iatrogenic and noniatrogenic injuries for women with invasive cervical cancer. It is important to emphasize, however, that cervical cancer screening is greatly beneficial for the early detection of cancer and is largely safe."

Women with cervical cancer may have increased risk of injury during diagnostic workup. Philadelphia, PA: American Association for Cancer Research; October 21, 2020. eurekalert.org/pub_releases/2020-10/aafc-wwc101920.php. Accessed January 8, 2020.

Researchers found that women who were diagnosed with invasive cervical cancer had an increased risk of injuries during diagnostic workups.

Women With Cervical Cancer May Have Increased Risk of Injury During Diagnostic Workup

According to 2 editorials in the journal 

, research in the nursing field has been critically influential to understanding evidence-based health care practice, care delivery, and policy during the coronavirus disease 2019 (COVID-19) pandemic. In order to investigate this influence further, researchers at the University of Pennsylvania School of Nursing assessed what the role of nursing research has been in supporting patients during the pandemic.

According to the authors of the guest editorial “Nursing Research Is Coronavirus Research

,” nursing practice has not only saved lives throughout the pandemic, but it has also played a critical role in understanding the nature of care for patients with COVID-19. The research conducted to understand this role further has helped to progress knowledge regarding the necessary elements of more supportive work environments that save patient lives and promote recovery in both hospitals and nursing homes.

Additionally, research in the field of nursing has helped to advance knowledge regarding how individuals sheltering at home with in-home nursing care are managing diets to support their health in light of chronic conditions, as well as how in-home nursing care has been able to stabilize chronic conditions during the pandemic.

The research in the field has also been able to bring to light lessons from the past around areas of concern for patients in order to positively impact policy around patient care during the pandemic.

"We know that nursing practice is saving lives in this pandemic. Nursing research also plays a critical role," write the authors of the guest editorial. “We support the move in universities to concentrate research on innovations directly related to the coronavirus crisis. But so much of nursing's research is coronavirus research. We applaud the search for reliable epidemiological data, effective treatments, and vaccines. We, though, must articulate nursing research's fundamental frame. We focus on the lived experiences of clinicians, patients, families, and communities.”

The author of the second editorial “How Effective Response to COVID-19 Relies on Nursing Research

,” Eileen T. Lake, PhD, the associate director of the Center for Health Outcomes and Policy Research and editor in chief of 

, explained further that throughout the pandemic, several clear challenges to an effective response to the public health crisis became evident. These challenges included the country’s restricted access to health care, the present surging demand for health care personnel, and the moral distress that many health care providers face during the pandemic.

Lake also noted that in order to better help institutions meet the demands that the COVID-19 pandemic posed to the health care system, nursing research was critical to effectively inform crucial elements of policy response and institutional preparedness.

"Nursing research provides answers during crises," writes Lake in the editorial. “In a time of profound upheaval, risk, and strain, it is reassuring to have evidence-based solutions to the challenges confronting our health care system and its clinicians.”

Nursing research informs response to COVID-19 pandemic. Philadelphia, PA: University of Pennsylvania School of Nursing; April 27, 2020. eurekalert.org/pub_releases/2020-04/uops-nri042720.php. November 30, 2020.

D’Antonio P, Naylor M, Aiken L. Nursing research is coronavirus research. 

Lake ET. How effective response to COVID‐19 relies on nursing research. 

2020;43(3):213-214. doi: 10.1002/nur.22025.

According to 2 editorials, research in the nursing field has been critically influential to understanding evidence-based health care practice, care delivery, and policy during the COVID-19 pandemic.