There is a higher incidence of treatment modifications or discontinuations in the neoadjuvant setting among Black patients compared with White patients who are receiving treatment for breast cancer, according to findings that were presented during the 2021 San Antonio Breast Cancer Symposium (SABCS).

However, results from this proof-of-concept study demonstrated that the use of a multiscale biophysical modeling platform may help identify what treatment outcomes may look like before clinicians and patients decide whether to modify their current treatment.

Researchers conducted a retrospective review of 173 patients who had received neoadjuvant therapy from January 2010 through March 2020 and separated the patients into 2 cohorts: 114 who received a scheduled regimen (SR) and 59 who received a modified regimen (MR). Although there were nearly double the amount of patients in the SR group than in the MR cohort, Black patients accounted for 59% of the MR cohort.

In the MR group, a significantly lower proportion of patients achieved a pathologic complete response (pCR) compared with the SR group (odds ratio, 0.44; 

 = .03). Moreover, similar to what has been observed in other studies, 42% of Black patients had treatment interruptions compared with 25% of White patients.

“During neoadjuvant therapy in breast cancer, treatment interruptions may impact rates of pathologic complete response and ultimately increase risk of recurrence,” the study authors wrote in their poster at SABCS.

Six patients (10%) had early discontinuation of doxorubicin and cyclophosphamide, 25 patients (42%) had an early discontinuation of a taxane therapy, 7 patients (12%) had an anti-HER2 therapy discontinued, and 21 patients (36%) had dose reductions throughout their therapy.

The study authors observed a pCR rate of 42% in the SR group and 20% in the MR group.

Utilizing the multiscale biophysical modeling platform, known as TumorScope, the researchers were able to use data from patients in the MR group and simulate what responses to treatment may have been if patients had received the full dose of their treatment uninterrupted. The simulation demonstrated that without treatment interruption, 10 additional patients (5.6%) would have been able to achieve a pCR. In the simulation, 100% of patients receiving SR had a complete response in comparison with 81.7% of those who would experience treatment interruptions.

TumorScope was previously evaluated in a separate study to determine its effectiveness and was used in several other studies and analyses presented at this year’s SABCS.

 According to the study researchers, the results show that TumorScope can be used to estimate the impact of variable dosing before clinicians decide to interrupt a patient’s treatment. Furthermore, researchers believe that TumorScope can evaluate individual treatments being considered for this patient population to support de-escalation of therapy ahead of time but note that further study is needed.

Pandey T, Pfeiffer J, Braun E, at al. Assessing the impact of treatment interruptions during neoadjuvant therapy in early stage breast cancer. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract P1-08-21.

SimBioSys presents new studies on its precision medicine software platform at the 2021 San Antonio Breast Cancer Symposium. News release. SimBioSys. December 1, 2021. Accessed December 8, 2021. https://bwnews.pr/3oz8qAP

Articles

Treatment modifications were inconsistent among White and Black patients with breast cancer. However, the use of a multiscale biophysical modeling platform may be useful in informing treatment modification decisions. 

Black Patients With Breast Cancer Experience Higher Rate of Treatment Modifications or Discontinuations

Patients with advanced hepatocellular carcinoma (HCC) demonstrated encouraging anti-tumor activity with a disease control rate (DCR) of 91% when treated with regorafenib (Stivarga) in addition to pembrolizaumb (Keytruda), according to a presentation at the 2021 virtual ASCO Annual Meeting.

Researchers looked at combing the 2 individual therapies, previously approved as monotherapies for patients with advanced HCC who progressed on sorafenib (Nexavar), in a phase 1b study (NCT03347292) that evaluated 35 patients with advanced HCC who had no prior systemic therapy. Treatment started with 120 mg of regorafenib daily on a 3 weeks on, and 1 week off schedule, and 200 mg of pembrolizumab given intravenously every 3 weeks. Treatment was planned to either escalate to 160 mg or lower to 80 mg of regorafenib, but only an exploratory cohort received 80 mg due to a high volume of dose modification in the 120 mg cohort. At the data cut off, 50% of the patients in the 80 mg cohort remained on treatment.

Response rates among both cohorts were similar; 31% of patients had an objective response rate (ORR) in the 120 mg cohort and patients in the 80 mg cohort had an ORR of 32%. Moreover, the 80 mg cohort had a median follow up of 10 months and displayed a median progression-free survival (PFS) of 6.9 months and a median time-to-progression (TTP) of 6.9 months, with insufficient follow up for overall survival (OS) data. In the 120 mg cohort, after a median follow up of 13.9 months, median OS, PFS, and TTP, was 26.5 months, 7.5 months, and 8.1 months, respectively.

Out of 32 evaluable patients in the 120 mg cohort 31% of patients had a partial response and 56% had stable disease with a DCR of 88%. Twenty-two patients in the 80 mg cohort had a higher DCR at 91% with 18% showing partial responses and 73% had stable disease.

“Overall, 57 patients were treated,” said Anthony B. El-Khoueiry, MD, from the Keck School of Medicine of USC and lead investigator of the study, at a virtual presentation of the data at the 2021 ASCO meeting.

“At baseline, most patients had an ECOG Performance Status of 0. All patients had Child-Pugh A and approximately 80% were BCLC stage C. And two-thirds had extrahepatic disease and/or microvascular invasion.”

In comparing the 2 cohorts, the 80 mg cohort had a more favorable safety profile and lower rates of dose reductions and treatment interruptions, according to El-Khoueiry. In the 120 mg cohort, two-thirds of patients had a treatment-emergent adverse event (TEAE) that led to interruption of treatment or dose reduction. Grade 3 or 4 TEAE occurred in 86% of patients in the 120 mg cohort compared with50% in the 80 mg cohort. The most common TEAE in both cohorts were AST increase (23% compared with9%), lipase increase (20%/5%), ALT increase (17%/9%), and hypertension (17%/9%). The majority of TEAE were linked with regorafenib in the 120 mg cohort at 66% of TEAEs compared with37% in pembrolizumab, however, in the 80 mg cohort 41% of grade 3 TEAEs were related to regorafenib compared with 23% in pembrolizumab.

“In Panel B, there was no apparent association between regorafenib exposure and objective tumor response, and there was substantial overlap in individual exposures,” explained El-Khouiery when talking about an additional biomarker analyses researchers completed. “The biomarker analyses were limited by small sample size and the lack of power to compare the 2 dose levels. Nonetheless, we did see a decrease in the ratio of CD4-positive to CD8-positive T cells from baseline, which was more apparent in the 120 mg cohort.”

El-Khoueiry A, Kim R, H W, et al. Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC). 

. 2021;39(suppl 15; abstr 4078). doi: 10.1200/JCO.2021.39.15_suppl.4078

El-Khoueiry A, Kim R, H W, et al. Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC). Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 4078.

This article was originally posted on OncLive as 

“Regorafenib/Pembrolizumab Combination Yields Encouraging Results in Advanced HCC”

A study of 2 cohorts shows that the combination of regorafenib and pembrolizumab is effective in generating anti-tumor activity in patients with HCC.

Regorafenib Plus Pembrolizumab Shows Promise in Treating Advanced HCC 

Gastrointestinal (GI) adverse events (AEs) that occurred in patients with metastatic breast cancer who were treated with oral paclitaxel and encequidar can be managed by the use of 5- HT3 inhibitors and early intervention with loperamide, according to research presented at the 2020 San Antonio Breast Cancer Symposium.

This combination regimen allows for fewer AEs, but investigators looked to find a way to prevent GI AEs that were found to be higher following treatment with oral paclitaxel and encequidar.

“Paclitaxel is substrate of the intestinal e-flux pump p-glycoprotein that leads to low oral bioavailbailty. Encequidar is a specific p-glycoprotein absorbed by patients to help bioavailbailty,” explained lead investigator Hope Rugo, MD, from the University California San Francisco Helen Diller Family Comprehensive Cancer Center, in a poster presentation at SABCS. “This avoids the need for Cremophor risk and allows for at home dosing with patients and eliminates the need for IV infusions.” However, she added, the incidence of gastrointestinal adverse events from this combination was high.

The researchers investigated preventive measures for GI AEs associated with oral paclitaxel and encequidar or IV paclitaxel — which were evaluated in a multinational trial looking at the safety of this combination in 442 patients.

Patients were randomized 2:1 on either oral paclitaxel and encequidar (205mg/m2/day x3 weekly) or IV paclitaxel (175 mg/m2 every three weeks) until disease progression or toxicity. The primary end point of the study was efficacy as defined by tumor response with secondary endvpoints of progression-free survival (PFS) and overall survival (OS).

All patients on IV paclitaxel (n = 111) were given dexamethasone and antihistamine premedication and after 30% (n = 70) of patients were enrolled to include those on oral paclitaxel and encequidar the protocol was amended to address the imbalance of GI AEs. Treatments included loperamide taken at home at the onset of diarrhea along with prophylactic anti-emetic therapy.

The most frequently prescribed anti-emetic therapies included ondanesteron, granisetron, palenosetron, aprepitant, metoclopramide, domperidone, and aprepitant. The majority of patients in the combination (59%) and monotherapy (54%) arms received ondanesteron.

After the amended use of prophylactic anti-emetic therapy, there was a marked decrease of grade 2 or higher vomiting and diarrhea in patients on oral paclitaxel and encequidar, from 24% to 7% and 27% to 16% respectively. A greater incidence of both AEs were seen in patients treated with IV paclitaxel.

Of note, prior to the amendment, overall GI AEs occurred less frequently in patients on IV paclitaxel compared to the combination regimen, with a rate of only 1% of grade 3 vomiting and diarrhea occurring. Grade 3 incidences prior to the amended treatment in patients on the oral regimen were 7% in vomiting and 9% in diarrhea, showing a slight decrease to 4% and 3%, respectively.

Rugo H, Umanzor G, Barrios F J et al. Oral paclitaxel and encequidar (oPac+E) in the treatment of metastatic breast cancer (mBC): management of gastrointestinal adverse events (GI AE). Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual.

This article was originally published on OncLive as, "

GI AEs Associated With Oral Paclitaxel Plus Encequidar Subside with Antiemetics, Loperamide in Metastatic Breast Cancer.

Managing GI AEs in Metastatic Breast Cancer

As COVID-19 cases continued to increase across the United States at the onset of the pandemic, many elective treatments and routine visits to hospitals and clinics were canceled or moved online. For patients with cancer, this has led to a transition to telehealth to make up for canceled visits. But not all visits can be conducted over a video call, mainly, cancer screenings.

, Pat Basu, MD, MBA discussed a “shadow curve” with the potential to further disrupt the cancer space as patients are forced to delay their screenings, which means that patients with cancer may not have their disease detected until it’s an later stage.

Basu, president and CEO of Cancer Treatment Centers of America, elaborated on the fear surrounding in-person cancer screenings during the pandemic and how to find the right balance between at home treatments and essential visits.

It seems that a lot of people don't see cancer screening as a necessity right now, and kind of fear that they're more in danger should they go in clinic, rather than just not getting screened at all. What would you say to those people who have those kinds of fears?

: I would say number one, I understand their fear in a world of uncertainty. It’s perfectly normal.

Number two, it's a false choice. Right now, in society, we're facing so many false choices. I won't go through all of them, but t's either black or white, right? It's either we don't treat your cancer and the patient dies from that or we know we just frivolously expose you to infectious diseases, so that's not the case.

Third, and perhaps most importantly, is you cannot miss your screening. You cannot miss your diagnosis. You cannot miss your treatment. There are 10 million people around the world this year that will die from cancer. One out of three Americans in their lifetime will be diagnosed with cancer. This year alone, about 1.7 million Americans will be diagnosed with cancer, the bedrock of therapy in cancer and for the last couple of decades has been catch it early, treat it consistently and treat it completely.

That has to be the case, or we are going to have hundreds of thousands, if not millions, of patients that are adversely affected by missing their cancer treatments, diagnosis or screening, if we don't take this seriously. So, I would just remind people that during crises there is a part of our brain that sort of takes over from the emotional, what's the near and dear kind of thing that is in the news all the time, right?

And in the news, all the time right now, is COVID-19. And it's a very serious illness. It's not to be ignored. But you know, 10 million and people around the world will be diagnosed with (and) will die from cancer. That's the story that's not being told consistently.

Knowing what we know now, do you think that there will be more of a focus moving forward on cancer treatments that can take place in a patient's home rather than in clinic?

I had helped co-found a telehealth company, and so, I'm a big fan of what telehealth can do, but I have a deep understanding of what telehealth cannot do.

In the year 2020 there are some things that can be done and some that I can't wait for the day when the iPhone can, you know, do surgery and radiation therapy but for now there’s a lot more we can do. Including remote monitoring to understand your symptoms, and potentially, we're exploring a lot of at home infusion of your medications.

So those types of things can be done for diagnosis and maintenance when it's done in a proper environment. But there is another consideration, which if you are in the active phase of treatment, that tumor needs to be surgically removed. It needs to be radiated, or you need to get the initial phase of the active chemotherapy treatment that requires you to come in and the best combination honestly is both.

At Cancer Treatment Centers of America, I believe that for the heavier part of the treatment, because there's no replacement to coming in, that the patient comes in. But then for surveillance, for maintenance and for some of those other things, they can get that through an at-home program.

Essential Visits or Telemedicine During COVID-19: Expert Offers Advice

The landscape for treating patients with indolent non-Hodgkin lymphoma continues to evolve, making it a challenge to optimize frontline and recurrent treatment, however, there are promising agents on the horizon, according to Brad S. Kahl, MD.

In the frontline setting alone, Khal, of the Siteman Cancer Center in St. Louis, explained that the first question that needs to be answered is whether a patient with indolent non-Hodgkin lymphoma (iNHL) needs to receive treatment immediately. This is because some patients are asymptomatic and have a low tumor burden, so they will not require treatment until symptoms develop or have a high tumor burden, explained Kahl.

Moreover, treatments used for iNHL vary between the lymphoma types, but typically in the frontline setting physicians use bendamustine (Bendeka) in combination with rituximab (Rituxan). This treatment is mostly well tolerated in patients; however, older patients can struggle with this combination and are then given single-agent Rituxan. Then, younger patients with a more aggressive form of iNHL would be better suited for a more in-depth combination treatment of Rituxan, cyclophosphamide (chemotherapy), doxorubicin (chemotherapy), vincristine (chemotherapy) and prednisone (R-CHOP).

“The management of [recurrent] indolent lymphoma is complicated because there are so many variables,” said Khal, in an interview with 

. "There are lot of treatment options and factors to consider, including a patient's age and fitness, their prior lines of therapy, and how well those previous therapies worked for them. It is hard to have a blueprint of how to manage these patients."

Managing patients with recurrent iNHL is also a matter of assessing the individual patient after their treatment as plans will vary based on a number of factors. For instance, maintenance therapy can weaken a patient’s immune system, explained Kahl, which can lead to hypogammaglobulinemia (a problem where not enough gamma globulins are produced in the blood which results in a low antibody count) that then leads to recurrent infections.

“Some physicians routinely administer maintenance therapy, others never do, and some make it optional. I tend to make it optional,” Kahl said. “I'll prescribe maintenance therapy to a patient, explain what it can do for them, and then [let the patient decide]. Maintenance therapy can extend a patient’s first remission, but it does not appear to impact overall survival (OS). If it did improve OS, all patients would receive maintenance therapy.”

One of the main challenges that Kahl cited for treating patients with iNHL, especially for recurrent indolent lymphoma, is trying to find agents with a longer durable response. Currently, the main treatment for these patients with recurrent indolent lymphoma is PI3K inhibitors and  ibrutinib (Imbruvica), drugs that target proteins related to cancer cell development, but the median progression free survival for patients on this therapy typically a year, according to Khal. Meaning patients will need another option after the first year.

New options are on the horizon, however, as researchers look at new antibody therapies and the use of CAR-T cell therapies. Kahl, also discussed the promise of immunotherapy agents that demonstrated responses in the 50-60% range, but cautioned patience as durability still needed to be assessed.

“We have a lot of options, which is a good problem to have. It does make the decision-making process more complicated, but I am grateful to have these options to manage patients with recurrent indolent lymphoma,” he said. “One needs to take a thoughtful long-term strategy when making these decisions for their patients.”

This article was originally published on CURE as, "

Evolving Treatment Landscape Presents Patients With Indolent Non-Hodgkin Lymphoma 'Lots of Options'.

Brad S. Kahl, MD, discusses the unique challenges that occur when treating patients with indolent non-Hodgkin lymphoma.
 

Options Expand for Indolent Non-Hodgkin Lymphoma

People who quit smoking at any time, even up to 2 years before a lung cancer diagnosis, have increased chances of survival after their diagnosis, according to data during a 2020 ASCO Virtual Scientific Program press briefing.

Researchers looked at data that included the time on smoking cessation from 17 International Lung Cancer Consortium (ILCCO) studies that made up a population of 35,428 patients with lung cancer. Researchers found that individuals who quit smoking more than 5 years before their lung cancer diagnosis had a 20% reduced risk of death from all causes, those who quit between 2 to 5 years prior to their diagnosis had a 16% reduced risk of death and those who quit less than 2 years before their diagnosis had a 12% reduced risk of death compared to current smokers.

"This research shows that if you're a smoker and you quit, no matter when you quit, you will be more likely to survive after being diagnosed with lung cancer, compared to someone who continues smoking," said Aline Fusco Fares, MD, lead author of the study and a clinical research fellow at the Princess Margaret Cancer Centre in Toronto. "The study's message is simple: quit smoking now."

In the study, researchers confirmed that there is a better overall survival among lung cancer patients who never smoked compared to those that did. However, former smokers can share these survival benefits as it is not “too late” for patients that were smokers prior to their lung cancer diagnosis.

Researchers found that the benefit of quitting smoking was also slightly greater among patients who smoked at least 20 cigarettes per day for over 30 years. These patients who smoked 20 cigarettes a day for at least a year were defined as heavy smokers, and researchers found that long-term heavy smokers who also quit smoking less than 2 years before, between 2 to 5 years before, and for more than 5 years before their lung cancer diagnosis had a 14%, 17%, and 22% reduced risks of death from all causes compared to non-smokers. However, for those that smoked less than 30 pack-years, the reduction rate was only significant for those that quit smoking at least 5 years before their lung cancer diagnosis.

"We saw a slightly bigger benefit to quitting among people who had smoked heavily for over 30 years compared with the overall population of former smokers. For long-term smokers, the benefits of quitting cannot be overstated," Geoffrey Liu, MD, MSc, a clinician scientist at the Princess Margaret Cancer Centre in Toronto and senior author on the study, said in a press release.

In a press briefing of the study, Fares explained that they want to use the time of a lung cancer screening to explain to patients the benefits of smoking cessation and showing patients that there is a marked survival benefit. Moreover, researchers found that the overall survival advantage of quitting smoking prior to their lung cancer diagnosis occurred in all subsets of patients studied including sex, lung cancer stage, histology, and a patient's pack years. Fares summed up the study as "it's never too late to quit smoking" imploring oncologists to explain this to their patients.

Fares A. Smoking Cessation and Lung Cancer outcomes: A survival benefit for recent quitters? A pooled analysis of 35,481 International Lung Cancer Consortium (ICLO) patients. Presented at: 2020 ASCO Virtual Scientific Program; May 12, 2020. Abstract 1512.

Regardless of Timing, Smoking Cessation Before Lung Cancer Diagnosis Shows Survival Benefit

Smoking Cessation Before a Lung Cancer Diagnosis Improves Outcomes

Cancer is a widespread disease that affects every population, yet none more so than the elderly. This patient population is growing at a pace that is overburdening cancer centers, and the duty of filling the gap created between aging patients and their care team is falling on oncology nurses.

Although there already is a shortage of nurses, even fewer are geriatric certified, making these training programs vital to the future of the oncology nursing field.

To understand the full scope of the care gap nurses are faced with bridging, it’s important to understand the phrase the “Silver Tsunami.” This nickname refers to the rising tide of the aging population flooding the healthcare system. On average, 10,000 Americans turn 65 each day, and 53.4% of all new cases of cancer involve patients 65 and up, with a median diagnosis age of 66, according to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program 2019 statistics.1

“The last of those baby boomers, those born between 1946 and 1964, will be turning 65 in 2030. And the estimate is [that] 1 in 5 of these baby boomers will be over 65 in 2030, so that’s a big group of people coming into the healthcare system in 2030,” explained Carolina Uranga, MSN, BSN, RN, AGCN-BC, OCN, WCC, ONS, in an interview with Oncology Nursing News®. However, healthcare has long known that the silver tsunami would crest in 2030.

Uranga, a clinical nurse specialist at City of Hope in Los Angeles, California, added that the majority of patients that nurses will see in a cancer clinic are elderly adults, and although 2030 feels far away, the gap in care is happening now and colliding with the current oncology nursing shortage.

“According to Dr Buerhaus in his article ‘Four Challenges Facing the Nursing Workforce in the United States,’ the acceleration of nurses retiring is estimated to be 1 million by 2030,” and this will create a brain drain in the healthcare system,” Uranga said.2 “Suffice to say, we aren’t graduating enough nurses also to keep up with the estimated demand. It’s really a vicious cycle because we don’t have enough nursing professors to provide the education, so we really can’t graduate enough nurses to keep up with the demand.”

Uranga pointed out that although less than 1% of nurses are geriatric certified, more schools are adding geriatric training to their programs, allowing all specialties within oncology to get the training they need to properly assess elderly patients.

A patient is considered geriatric at 65 because at this age, Social Security and Medicare benefits kick in, but this chronological age does not always equate to a patient’s functional age, according to Uranga.

At the 37th Annual Chemotherapy Foundation Symposium (CFS®), hosted by Physicians’ Education Resource®, Uranga presented on a geriatric training and assessment program done through City of Hope that recently received Cancer Research Education Grants Program (R25) support for a funding effort that her and her colleagues were spearheading.3

One of the program’s pillars involves educating nurses to understand that age 65 does not have to be a medical cutoff for treatments and that patients younger than 65 may function worse than someone older. Each patient is different, with a different cancer, so the care they need will be unique.

“Maybe [with a] patient you thought you couldn’t be aggressive with, you do a geriatric assessment…and find that this patient can tolerate an aggressive treatment versus decreasing the dose,” Uranga explained during her presentation. “Some older patients can do a lot more and are very active, so assessing the fitness of the older adult versus their frailty will go a long way in making those decisions.”

This approach to personalized care for geriatric patients has also changed the oncology nurse’s role at the bedside. In an interview with Oncology Nursing News®, Paola Bueno, RN, a clinical nurse at City of Hope and a participant in the R25 grant program, discussed how she approaches geriatric patients. “We perform some assessments that help determine any age-related sensory changes that patients might have, such as auditory [or] visual, or limitations on mobility,” she said.

Implementing these tests has led to a better workflow, Buneo said, because it gives the care team a validated tool that can help create personalized care plans prior to undergoing the rigors of cancer treatment. These assessments are often not time-consuming and are simple for the patient to use. For example, the Timed Up & Go assessment takes 3 minutes or less, and nurses need just a chair, a stopwatch, and 10 feet of space. The nurse times the patient walking 10 feet from the chair and back; according to the certified test, 12 seconds or more indicates a risk of falls and also gives the nurse the chance to observe the patient’s gait and consider how adverse effects from treatment might affect mobility.3

Ultimately, Uranga and Bueno hope that a better understanding of what it takes to help a geriatric patient will lead to more positive outcomes as oncology nurses bear the brunt of the Silver Tsunami.

As the number of elderly oncology patients rises rapidly, nurses need training to properly assess their needs.

Nurses Face Challenge of Closing Gap in Geriatric Care

About 10,000 Americans turn 65 each day, bringing on what some call a "silver tsunami" of geriatric patients flooding the healthcare system. However, less than 1% of nurses are geriatric certified.

For this month's episode, we'll hear from Carolina Uranga, MSN, BSN, RN, AGCN-BC, OCN, WCC, ONS, clinical nurse specialist at City of Hope, and Paola Bueno, RN, clinical nurse at City of Hope, about a program they used -- as well as other resources -- to improve their care of geriatric patients, a skill that nearly all oncology nurses will need to have.

There's a title wave of older adults flooding the healthcare system. Hear from two oncology nurses on how practitioners can be preapred to give high-quality care.

Preparing Nurses for the 'Silver Tsunami'

Findings from the phase III CheckMate-067 trial, which investigated the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) to treat patients with advanced melanoma, showed potential biomarkers in patients who achieved a complete response at 5 years, according to Georgina V. Long, PhD, BSc, MBBS, FRACP.

Long, co-medical director of Melanoma Institute Australia (MIA), chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, University of Sydney, presented these findings at the 16th International Congress of the Society for Melanoma Research (SMR). She discussed how the patients were alive at 5 years were an enriched population more likely to achieve a complete response.

Long also had the chance to sit down with 

, and discuss the findings of the study along with toxicities that oncology professionals should look out for during the course of the treatment. 

: What are the current treatment options for patients with advanced melanoma?

For people with advanced melanoma, the approved drugs in many countries around the world include 2 types of treatments, immunotherapy and targeted therapy. The targeted therapies are BRAF plus MEK-inhibitors for those who carry the BRAF mutation in their tumor — that’s about 40% of all advanced melanoma patients. The immunotherapies work in all patients whether they're BRAF wildtype or BRAF mutant.

Now I should qualify that the immunotherapies don't work in all patients, but they're potentially available for all patients. The immunotherapies include checkpoint inhibitors, the CTLA-4 and anti-CTLA4 with ipilimumab, and anti-PD1 with either nivolumab or pembrolizumab. We also have the combination of ipilimumab with nivolumab as an option for patients.

What were some of the findings from studying this combination?

When we looked at the descriptive analysis of subgroups, those alive at 5 years are an enriched population, more likely to have had a complete response, are more likely to have had a lower LDH or a normal LDH baseline and are more likely to have a lower numbers of metastatic sites. That's a marker of lower volume of disease, and that's what we see across all the drug treatments we now use in melanoma.

Patients who get a complete response have low volume of disease in a normal LDH baseline, and tend to do better on all our drugs. And indeed, we see this with both the combination of nivolumab plus ipilimumab and nivolumab alone.

So that was one finding from the study — 5 years survivors are enhanced with patients like that. It doesn't mean that if you have poor prognostic features you won't be alive at 5 years. You can, it's just enriched for those sorts of patients. The other thing we looked at in the study was how well do people do based on their response, their resist response. So, we found that for patients who had a complete response, 80% of them remained in complete response at 5 years, and that was also the same for nivolumab. Eighty percent was nivolumab combined with ipilimumab 79% of those who had a complete response on nivolumab had not progressed by 5 years.

What is the toxicity profile of this combination?

We do see toxicity with the combination compared with the monotherapy nivolumab. Nivolumab combined with ipilimumab we see a rate of grade 3-4 treatment related adverse events just under 60%. Many of those are reversible with corticosteroids.

The ones that are not reversible tend to be the endocrinopathies, that's thyroid or hypopituitary and rarely type-1 diabetes, but they can be managed with replacement drugs. So, for example, replacement thyroid hormone, and replacement corticosteroids and for type-1 diabetes insulin. Although that can be an impact on people's quality of life.

So, it's certainly more toxic, but we see fewer grade 3 for a treatment related adverse events with nivolumab alone. Again, a similar pattern though, I mean, we're talking less than 20% grade 3-4 but a similar pattern, in that, most of the side effects are reversible with cessation of treatment, sometimes you need steroids to reverse them, but the endocrinopathies are not reversible, but you are able to replace the hormone.

Recent findings showed patients with advanced melanoma had a favorable complete response to nivolumab and ipilimumab due to potential biomarkers in the disease.

Nivolumab/Ipilimumab Shows More Promising Results in Patients with Melanoma

In a recent study titled, “Palliative Care and Moral Distress: An Institutional Survey of Critical Care Nurses,” researchers found that respondents experienced more moral distress while in the clinic and if they had less perceived use with palliative care.

Fewer than 40% of respondents reported being highly component in any type of palliative care, and 38% of those respondents reported not having any palliative care education in the past 2 years.

Researchers concluded that due to this lack of training, when nurses perceive their ability to provide palliative care is inadequate and are asked to provide this care, they are more prone to feeling moral distress. This moral distress not only impacts their work, but can also affect their home lives creating psychosocial damage detrimental to a nurses’ wellbeing, and while this study is focused on critical care nurses, these issues within palliative care extend to the oncology nurse.

“While this is a critical care group, the findings are extremely relevant to the oncology population and oncology nurses across settings,” said Betty Ferrell, PhD, MA, FAAN, FPCN, director of the Division of Nursing Research and Education at City of Hope, in an 

 addressing the use of education to help palliative care practices.

“There have been similar studies like this, including in the oncology nursing space, and generally all of those studies have had very similar findings that nurses are not prepared to care for very sick or dying patients,” Ferrell explained, highlighting that moral distress for nurses in these situations comes from the gap of knowing the care that is right to deliver and the care that the nurse is prepared to deliver.

This is where further education needs to step in to fill the gap, like the 

End-of-Life Nursing Education Consortium (ELNEC)

, a program that Ferrell was the principal investigator on, and co-author of the study Kenneth R. White, PhD, RN, ACNP, ACHPN, has recommended for any nurses engaged with palliative care. 

White, professor of nursing and medicine and Associate Dean of Strategic Partnerships and Innovation, School of Nursing, University of Virginia, and a palliative care nurse practitioner, University of Virginia Medical Center, Charlottesville, Virginia, had the chance to speak with 

 and discuss the findings of the study and how education and collaboration is essential for health systems to help address the moral distress nurses are experiencing. 

®&#8203;&#8203;&#8203;&#8203;&#8203;&#8203;&#8203;

Can you briefly describe the objectives of this study?

: We sought to find out more about what critical care nurses viewed as their self-assessed level of palliative care knowledge and competency.  A second objective was also assessing 

the respondent’s self-perceived moral distress.

How did this study come about, and where was the need for this study first identified?

Alex Wolf was obtaining his DNP degree from UVA and focused his education on palliative care. He is a critical care nurse by experience and sought to learn more about critical care nurses’ perceptions of palliative care.  He had observed in his own practice that critically ill patients were not always given the option for palliative care when facing complex chronic illness.  Two of the faculty co-authors (White and Epstein) had developed a survey instrument, “Palliative Care Competencies of Registered Nurses,” which was used to gather information for the results.

Aside from having health system leaders prioritize palliative care training, are there any resources for nurses to use to help increase their understanding of palliative care?

Yes! The ELNEC is a national program that is focused on increasing knowledge in the palliative care domains. ELNEC is designed for specific patient populations and has “train-the-trainer” programs for replication and rapid spread. There are many other resources available such as the Clinical Practice Guidelines for 

. (The AACN also provides its own list of 

palliative care and end-of-life clinical resources

For respondents and other nurses experiencing moral distress from being unable to provide proper palliative care, how would you advise them to help treat their own moral distress?

It is important to find someone to talk to when a person experiences moral distress in their practice. It may be a colleague, a nurse manager, or a member of the ethics consult service. At UVA, nurses have championed a palliative care group in order to learn more about palliative care and to have a voice with other professional colleagues in improving access to palliative care. 

While the study focused on nurses in the intensive care unit, how do you think these findings may apply to palliative care training in the oncology nurse setting?

The survey that was used in this study was adapted for critical care nurses from a study that was originally designed for oncology nurses. The results of two national studies that surveyed oncology have been 

The findings with the critical care nurses are similar to the findings with oncology nurses. The most often cited knowledge gap is how to talk with patients and families about death and dying.

What do you hope happens for the future of palliative care?

Although it is important for nurses to have more knowledge about palliative care and to be able to recognize signs of moral distress, it is also important that nurses and physician colleagues collaborate and practice inter-professionally. It has been shown that when nurses have more knowledge about palliative care, the moral distress 

increase when their patients are not receiving the best care possible, which may include palliative approaches. Palliative care is a discipline that must be learned and practiced inter-professionally.

Wolf AT, White KR, Epstein EG, Enfield KB. Palliative care and moral distress: an institutional survey of critical care nurses. Critical Care Nurse. 2019;39(5):38-50.

New findings show that while nurses need to provide more palliative care to patients, they are not prepared to do so, leading to high levels of moral distress.

Conor Killmurray