This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.


Advanced practice nurses, registered nurses, and other health care professionals who care for cancer patients may participate in this CE activity.

Upon completion, participants should be able to:

• describe new preventive options and treatments for patients with cancer

• identify options for individualizing the treatment for patients with cancer

• assess new evidence to facilitate survivorship and supportive care for patients with cancer

ACCREDITATION/CREDIT DESIGNATION STATEMENT


Physicians’ Education Resource®, LLC, is approved by the California Board of Registered Nursing, Provider #16669, for 1 Contact Hour.

It is the policy of Physicians’ Education Resource®, LLC (PER®), to ensure the fair balance, independence, objectivity, and scientific objectivity in all of our CE activities. Everyone who is in a position to control the content of an educational activity is required to disclose all relevant financial relationships with any commercial interest as part of the activity planning process. PER® has implemented mechanisms to identify and resolve all conflicts of interest prior to release of this activity.The planners and authors of this CE activity have disclosed no relevant financial relation-ships with any commercial interests pertaining to this activity.

1. Read the articles in this section in their entirety.

3. Complete and submit the CE posttest and activity evaluation.

This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other health care provider relative to diagnostic, treatment, or management options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®.

Awareness of Tepotinib-Associated Adverse Events May Optimize NSCLC Outcomes

Nurse-specific recommendations highlighting potential adverse events associated with tepotinib treatment may help increase time on treatment and lead to improved outcomes.

Guidance created for nurses provides strategies to identify and manage common adverse events (AEs) in patients receiving tepotinib (Tepmetko) to treat non–small cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping, according to a poster presented at the 46th Annual Oncology Nursing Society Congress, held April 20 to 29, 2021.

Tepotinib is a MET tyrosine kinase inhibitor recently approved for the treatment of patients with NSCLC with METex14 skipping, which occurs in 3% to 4% of patients with this cancer.

“As with any anti-cancer therapy, it is important to promptly identify, prevent, and manage any adverse events,” Terri Alexander, MS, research nurse supervisor at The University of Texas MD Anderson Cancer Center in Houston, said during the presentation. “This can help minimize dose modifications [and] discontinuations and ensure that patients get maximal benefit from therapy. Effective AE management can also support patient quality of life. Within the multi-disciplinary team, nurses play an important role in AE management.”

Alexander and colleagues developed nurse-specific visual guidance for the early identification and management of the most common AEs associated with tepotinib therapy for NSCLC. This guidance was based on an analysis of AEs observed in 255 patients with METex14-skipping NSCLC in the VISION trial (NCT02864992), in addition to real-world nursing experience.

The AEs included in the guidance are peripheral edema; creatinine increase; gastro-intestinal AEs such as diarrhea, vomiting, and nausea; pleural effusion; interstitial lung disease; and liver enzyme elevations. Information about the frequency of each AE is provided, and strategies for monitoring and management are recommended.For example, the investigators note that low-grade peripheral edema is a common AE, even in fit patients; however, progression to established edema can make treatment more difficult. By routinely performing the monitoring steps described in the guidance (such as checking for skin erosions and weight gain), nurses can identify edema early and mitigate it using the suggested conservative management approaches, which include compression stockings and limb elevation.

“These recommendations can support nurses in timely and effective management of AEs with tepotinib,” Alexander said during the presentation. “Proactive approaches to mitigate AEs may help to improve quality of life. In addition, by increasing time on treatment, AE management may help improve outcomes for this elderly patient population.”

Alexander T, Ahn L, Berghoff K, Vlassak S, Lemmens L. Managing side effects of tepotinib treatment to optimize outcomes for patients with non-small cell lung cancer harboring METexon 14 skipping: expert guidance based on clinical experience. Presented at: 46th Annual Oncology Nursing Society Congress; April 20-29, 2021; Virtual. Abstract 8970. Accessed April 15, 2021. https://ons.confex.com/ons/2021/meetingapp.cgi/Paper/8970

NPs Play Crucial Role in Helping Patients With uHCC Avoid Premature Discontinuation of Lenvatinib

Nurse practitioners should educate patients and caregivers about how to manage key adverse reactions associated with lenvatinib to help ensure patients remain on treatment to maximize benefit.

Nurse practitioners (NPs) should routinely follow up with patients with unresectable hepatocellular carcinoma (uHCC) who are receiving treatment with lenvatinib (Lenvima) to help prevent premature discontinuation of therapy as a result of serious adverse events (AEs), according to study results presented in a poster at the 46th Annual Oncology Nursing Society Congress, held April 20 to 29, 2021.

“Nurse practitioners play a critical role in providing education, as well as monitoring for and managing adverse reactions that may arise during therapy, thereby alleviating patients’ and caregivers’ concerns about initiating and maintaining treatment,” said lead study author Anna Jones, FNP-C, of Pacific Hematology Oncology Associates in San Francisco, California, during a recorded presentation of the data.

Jones and colleagues conducted a post hoc analysis of data from the phase 3 REFLECT trial (NCT01761266), which led to the FDA approval of lenvatinib in previously untreated patients, to characterize key AEs associated with treatment and assess strategies to manage them. A focus of their report was the crucial role NPs play in educating patients regarding the management of AEs.

Jones noted that although lenvatinib was found to be noninferior to sorafenib (Nexavar) in terms of median overall survival, the primary end point of the REFLECT trial (13.6 months vs 12.3 months; HR, 0.92; 95% CI, 0.79-1.06), important secondary end points, such as progression-free survival, time to progression, and objective response rate, improved significantly with lenvatinib treatment (P < .0001).

Almost all (99%) of the 476 patients treated with lenvatinib in the REFLECT trial experienced treatment-emergent adverse events (TEAEs), with 75% of patients experiencing TEAEs of grade 3 or higher. The most common TEAEs were hypertension (45%), diarrhea (39%), and decreased appetite (34%). An evaluation of dose modifications due to treatment-related AEs revealed a 40% rate of dose interruptions, 37% dose reductions, and 9% premature treatment discontinuation among patients taking lenvatinib. Early AE recognition and management, Jones emphasized, is imperative to ensuring patients remain on therapy to maximize the benefits of lenvatinib. 

Characterization of Adverse Reactions and Their Frequency

Jones and colleagues reviewed the key adverse reactions (ARs; grouping of AEs per FDA definitions) that most frequently resulted in either dose reductions or interruptions of lenvatinib treatment. These ARs included fatigue, hyper-tension, palmar-plantar erythrodysesthesia syndrome, proteinuria, decreased appetite, and diarrhea. Of note, the investigators determined that these ARs all had a median time to first onset that was less than 10 weeks after treatment initiation. Median time to first onset was shortest for fatigue (3.4 weeks) and hypertension (3.7 weeks) and was longest for diarrhea (9.6 weeks) and decreased appetite (6.8 weeks).

 Among the key ARs, proteinuria (7%) and fatigue (6%) most often led to lenvatinib dose interruptions; fatigue (7%), decreased appetite (6%), and diarrhea (6%) most frequently led to dose reductions.“

Knowledge of this information is crucial for nurse practitioners to make patients and care-givers aware of when to expect these [adverse] effects and to review ways to alleviate them, as well as when to contact the health care team,” explained Jones. “Through identification of potentially problematic comorbidities and routine check-ins, nurse practitioners [can] ensure that patients do not discontinue lenvatinib prematurely.”

NP Suggestions for Managing Key Adverse Reactions

Jones highlighted sections of the poster featuring NP perspectives on how to manage hypertension, diarrhea, and fatigue—ARs that may negatively impact on quality of life and result in premature lenvatinib discontinuation. The recommendations for hypertension management included identifying patients with preexisting hypertension and making sure the condition was controlled before initiating lenvatinib.

Among strategies for fatigue management was a recommendation that preexisting fatigue due to a treatable cause should be addressed both before and during therapy. Moreover, NPs should be mindful that fatigue may be caused by a patient’s decreased appetite (which may be an effect of lenvatinib therapy). Lenvatinib-associated fatigue may be managed by treatment modification, which should depend on the severity of the patient’s fatigue.

Appropriate dosing of concomitant medications such as lactulose is critical for prevention of diarrhea. For patients who nonetheless experience this AR, NPs may suggest the “bananas, rice, apples, and toast (BRAT)” diet to solidify stools. Additionally, patients should be counseled on the importance of sufficient hydration to replenish electrolytes lost through diarrhea.

Because they are often the primary point of contact for patient education, NPs are well positioned to reassure patients that they will receive the best tolerated dose of lenvatinib. According to the investigators, this will help patients stay on treatment longer to derive the maximum therapeutic benefit.

A crucial aspect of patient education by NPs is discussing common ARs patients may experience and offering suggestions for managing them at home. It is also important for NPs to help patients identify situations that require a call or visit to the clinic or emergency services for symptom management.

“I hope this presentation will provide meaningful information to further advance your clinical practice and enhance patient understanding and adherence of lenvatinib treatment for uHCC,” concluded Jones.


Jones A, Moore A, Robbins C, Amaya-Chanaga C, Sung MW, Baron AD. Patient education and management of adverse reactions in patients with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib: nurse practitioners’ perspective. Presented at: 46th Annual Oncology Nursing Society Congress; April 20-29, 2021; Virtual. Abstract 9403. https://ons.confex.com/ons/2021/meetingapp.cgi/Paper/9403

Articles

CE lesson worth 1 contact hour that is intended to advanced practice nurses, registered nurses, and other healthcare professionals who care for patients with cancer.

Continuing Education: June 2021

Utilizing a dose escalation strategy, as well as preemptive use of a steroid cream and close follow-up within the first few months of initial treatment with Stivarga (regorafenib) may reduce side effects from the tyrosine kinase inhibitor (TKI) while improving quality of life, according to Dr. Tanios S. Bekaii-Saab.

Stivarga confers an improved survival benefit in patients with refractory metastatic colorectal cancer; however, side effects, like hand-foot skin reaction, may occur within the first two to three weeks after treatment initiation, with the most severe events occurring after week three or four. These common toxicities can be expected with oral TKIs, like Nexavar (sorafenib), but most of the toxicities tend to come a little bit later with those agents, Bekaii-Saab explained.

“The (idea) is, as you're starting the patient on treatment, those that are able to continue through it will see the benefits. Unfortunately, because of the early toxicities, a lot of patients end up stopping treatment prematurely, understandably so,” he added.

Hand-foot skin reaction, for example, causes redness, swelling and pain on the palms of the hands and/or the soles of the feet, which could limit walking or the use of one’s hands. “You can imagine that's incredibly disruptive,” said Bekaii-Saab, medical oncologist, leader of the Gastrointestinal Cancer Program at the Mayo Clinic Cancer Center, medical director of the Cancer Clinical Research Office and vice chair and section chief for medical oncology in the Department of Internal Medicine at the Mayo Clinic in Phoenix.

Therefore, he and his colleagues felt there was a need to determine ways to negate these toxicities so patients could stay on treatment with Stivarga in order to maximize the benefit of its improved survival outcomes.

“Most survival reported on this agent and similar agents is about six months, on average. In this case, you double the survival if you're able to get them to cycle three. So, we need strategies that mitigate some of the toxicities that ultimately have the patient stop the drug too prematurely and appear to negatively affect the overall outcome,” Bekaii-Saab said.

In the randomized, multicenter, open-label, phase 2 Regorafenib Dose Optimization Study (ReDOS) trial, the researchers evaluated four groups of patients treated with Stivarga:

54 patients were treated with a dose-escalation strategy: a starting dose of 80 mg per day orally, with weekly escalation of 40 mg each week, as tolerated, until a dose of 160 mg per day was reached.

62 patients were treated with a standard-dose strategy of 160 mg per day orally for 21 days of a 28-day cycle.

61 patients were preemptively treated with 0.05% clobetasol cream twice daily, applied to palms and soles before Stivarga treatment.

55 patients were reactively treated with 0.05% clobetasol cream twice daily, applied to palms and soles during Stivarga treatment.

They aimed to determine the proportion of patients who initiated cycle three of treatment.

After a median follow-up of 1.18 years, 23 patients (43%) treated with the dose escalation strategy and 16 patients (26%) treated with the standard dose initiated cycle three of treatment. The most common side effects experienced by those treated in the dose escalation and standard dosing strategies were fatigue (13% versus 18%, respectively), hand-foot skin reaction (15% versus 16%), abdominal pain (17% versus 6%) and hypertension (7% versus 15%). In addition, 14 patients had at least one drug-related serious side effect: six patients in the dose-escalation group and eight patients in the standard-dose group.

“With (dose escalation) by itself, it did not only improve the outcomes, meaning patients were more likely to stay on treatment, they're more likely to benefit from treatment and their survival was increased by an average of four months, at least,” Bekaii-Saab said. “But what we've seen also is a significant cut in toxicities as well as in the likelihood of the patients discontinuing treatment.”

When evaluating the use of clobetasol cream, 30% of those who followed the preemptive use strategy had no evidence of hand-foot skin reaction, compared with 13% who used the cream reactively during the first two cycles of treatment. During the first cycle, 54% and 45% of patients, respectively, had no hand-foot skin reaction, and 33% and 15% did not experience the side effect in the second cycle. During the second cycle, rates of grade 1, 2 and 3 hand-foot skin reaction were 30%, 8% and 3%, respectively, with preemptive clobetasol and 43%, 18% and 7%, respectively, with reactive clobetasol.

Moreover, patient-reported outcomes showed that the side effect compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol.

Bekaii-Saab noted that this finding has changed his practice in treating patients with Stivarga. “For many of my patients, now I do preemptive steroids. Ultimately, I think this is going to become a practice for every single one of our patients that goes on regorafenib,” he said. “We're even using it, based on this data, with other tyrosine kinase inhibitors. So this has expanded beyond regorafenib. This has changed, for all patients I hope, how we bring out some of these toxicities that can be incredibly limiting to quality of life.”

Ultimately, he added, the dose escalation strategy should be the standard of delivering Stivarga to patients, as well as the use of preemptive steroid creams. Lastly, Bekaii-Saab noted the importance of follow-up, in particular with the increased use of telemedicine following the COVID-19 pandemic.

“It has made it much easier for us to check on patients without bringing them to the clinic. The first month, my pharmacist, my nurse, and when possible myself, we get in touch with the patient,” he said, adding that follow-ups are the “third shield that will prevent those patients from going through a worse outcome.”

“They're already suffering from the cancer, we just want to make their lives better, not make it worse. And I think that if we don't do all the right things, we may actually impede their quality of life. If we do all the right things, then their quality of life is preserved and their survival is significantly improved. And they're more likely to get through more lines of therapy, which extends their survival significantly. So it's important. Cream, dose escalation strategy and close follow up are the three tenets of getting those patients through treatment.”

Although Stivarga may cause side effects after initial treatment, a dose escalation strategy and the preemptive use of steroid creams may help patients to tolerate the regimen better, while allowing them to capitalize on the agent’s survival benefit.

Three Tenets to Prevent Stivarga-Related Side Effects, Improve Survival and Quality of Life

 This activity is provided free of charge.

This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.

Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may participate in this CE activity.

Describe new preventive options and treatments for patients with cancer

Identify options for individualizing the treatment for patients with cancer

Assess new evidence to facilitate survivorship and supportive care for patients with cancer

Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 1.0 Contact Hour.

It is the policy of Physicians' Education Resource®, LLC (PER®) to ensure the fair balance, independence, objectivity, and scientific objectivity in all of our CE activities. Everyone who is in a position to control the content of an educational activity is required to disclose all relevant financial relationships with any commercial interest as part of the activity planning process. PER® has implemented mechanisms to identify and resolve all conflicts of interest prior to release of this activity.

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

This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other health care provider relative to diagnostic, treatment, or management options for a specific patient's medical condition.

The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®

Mutations, irAEs May Help PredictImmunotherapy Response in NSCLC

Patients with non–small cell lung cancer (NSCLC) who experience immune-related adverse events (irAEs) may have better survival outcomes than those without irAEs, according to research presented at the IASLC 2020 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, held January 28 to 31, 2021.

Overall, 30 Hispanic and 97 non-Hispanic patients were involved. Neither 

 mutations nor irAEs were found to occur at significantly different rates between these 2 patient groups.

 gene mutation had shorter median overall survival (OS) than those with wild-type 

 double mutation was also correlated with a lower 12-month OS rate compared with doubly wild-type tumors.

The investigators retrospectively analyzed the outcomes of patients with stage IIIB/IV NSCLC who were tested for mutations in the 

 genes and who were treated with immune checkpoint inhibitors between July 2014 and November 2019. In addition to examining the role of 

 mutations and irAEs in predicting immunotherapy response, the research team sought to compare the incidence of 

 mutations and irAEs between Hispanic and non-Hispanic patients.

The study population included 96 patients with 

 mutation. Both groups had a median age at diagnosis of 65 years. Forty-eight patients experienced an irAE (median 70 years old at diagnosis), and 77 patients were irAE negative (median 66 years old at diagnosis). Overall, 30 Hispanic patients were involved: 8 harbored an 

Median OS was significantly longer in patients who were 

-mutant group (12.1 vs 8.6 months, respectively; HR, 1.7; 95% CI, 1.0-3.6; 

= .03). The wild-type group also had a higher 12-month OS rate (73% vs 55%; 

 wild-type cancer had slightly better median progression-free survival (PFS) (6.3 vs 5.6 months; HR, 1.35; 95% CI, 0.76-2.1; 

-mutant group, though the differences were not statistically significant.

 had a significantly higher 12-month OS rate compared with patients harboring both mutations (70% vs 40%, respectively; 

However, median OS did not differ significantly between the 2 groups (11.4 vs 5.3 months; HR, 1.8; 95% CI, 0.69-4.62; 

= .13), nor did median PFS, at 5.1 months in the fully wild-type group and 3.0 months in the double-mutant group (HR, 1.2; 95% CI, 0.58-2.54; 

 mutations did not differ significantly between Hispanic and non-Hispanic patients (26.7% vs 23.7%, respectively; OR, 1.2; 95% CI, 0.46-3.0; 

Effects of irAE Status on Survival Outcomes

Patients who experienced an irAE had significantly better PFS and OS outcomes.

Median PFS was 9.5 months in patients who had an irAE compared with 4.4 months in those who did not (HR, 0.54; 95% CI, 0.35-0.82; 

 = .005). Twelve-month PFS was also significantly better in irAE-positive patients than in irAE-negative ones (60% vs 33%, respectively; 

Median OS was 14.2 vs 7.3 months in the irAE-positive and -negative groups, respectively (HR, 0.35; 95% CI, 0.20-0.61; 

 < .001). Twelve-month OS was also significantly higher in patients who had an irAE compared with those who did not (85% vs 60%; 

The rate of irAE positivity did not differ significantly between Hispanic and non-Hispanic patients (46.7% vs 35.8%, respectively; OR, 1.6; 95% CI, 0.68-3.5; 

 = .29). Similarly, the irAE-positive patients in the 2 groups did not have significantly different rates of the most common irAEs: hypothyroidism (35.7% vs 14.7%; 

This study’s findings provide additional support for the use of irAE and 

 mutation status to better identify patients who may respond to immune checkpoint inhibitors. The investigators also suggested further evaluation of their findings in larger studies in the future.

Raez LE, Uba R, North A, et al. STK11/LKB1, KRAS mutations and immune-related adverse events as predictors of response to immunotherapy in lung cancer. Presented at: IASLC 2020World Conference on Lung Cancer; January 28-31, 2021; Virtual. Poster P33.14. Accessed January 31, 2021.

Virtual Prehabilitation Is Efficacious Before Lung Cancer Surgery 

Virtual prehabilitation may improve patients’ physical activity level and exercise capacity before they undergo lung cancer surgery, according to recent research presented at the IASLC 2020 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, held January 28 to 31, 2021.

“Prehabilitation is the practice of enhancing a patient’s functional capacity before surgery, with the aim of improving postoperative outcomes,” explained lead study author Stephanie Wynne, BSc, psychical therapist at Guy’s and St. Thomas’ NJH Foundation Trust in London, England while presenting the data. “In lung cancer surgery, [prehabilitation] is associated with improved functional capacity and quality of life and reduced hospital length of stay, postoperative complications, and readmission.”

Wynne explained that lung resection is the most common radical treatment for lung cancer, yet only 10% to 30% of individuals referred are actual candidates for the procedure “due to their disease stage and a number of surgical risk factors, including advanced age, performance status, high comorbidities, and reduced cardiopulmonary reserve.” Prehabilitation may help increase patients’ presurgical physical fitness.

Although prehabilitation typically occurs in a face-to-face setting, an at-home option is particularly attractive during the COVID-19 pandemic.

A study was conducted during the summer of 2020 that included 20 patients who were about to undergo lung surgery at a National Health Service Trust in London, England. They were all given a personalized home-based exercise program and a diary to monitor compliance. Patients also received written advice and counseling for symptom management and participated in virtual follow-ups every 1 or 2 weeks via telephone or video.

The majority (65%) of participants were female, and the average age was 68 years. The preintervention assessment revealed that 45% of patients had 5 or more comorbidities, 70% had a history of smoking, and 15% were classified as “vulnerable-mildly frail” per the Rockwood Clinical Frailty Score.

Participants were assessed before and after the intervention on the following outcomes:

Continuing Education: April 2021

Videos

Metastatic CRC Nursing Webinar

This activity is provided free of charge.

, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 1 Contact Hour.

It is the policy of Physicians’ Education Resource

) to ensure the fair balance, independence, objectivity, and scientific objectivity in all of our CE activities. Everyone who is in a position to control the content of an educational activity is required to disclose all relevant financial relationships with any commercial interest as part of the activity planning process. PER

 has implemented mechanisms to identify and resolve all conflicts of interest prior to release of this activity.The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial interests pertaining to this activity.

Read the articles in this section in its entirety.

Complete and submit the CE posttest and activity evaluation.

This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other healthcare provider relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER

Preventing the Spread of Clostridioides Difficile in Oncology Units

Hospital-acquired infections can negatively affect outcomes in patients with cancer, so it is imperative that oncology nurses are vigilant about preventing them. After seeing a spike in Clostridioides difficile (C diff) infections a few years ago, nurse investigators at City of Hope National Medical Center in Duarte, California, conducted a root cause analysis and then created an intervention plan to stop the spread.

The results were presented by Karen Wohlgezogen, BSN, RN, CPHON, assistant clinical nurse manager at City of Hope, during the 2020 Oncology Nursing Society Bridge virtual conference, held September 8 to 17, 2020.1

“C diff is a spore-forming [bacterium] that is very resilient and difficult to kill,” Wohlgezogen said. “It causes life-threatening diarrhea and colitis.”

In their initial analysis, the investigators realized that C diff infections were occurring in adjacent rooms during the same time frame, which suggested a role of staff in spreading the infection, Wohlgezogen explained, also noting that some staff members were unable to correctly answer questions about how to adequately clean shared equipment. They also noticed family members of patients in isolation rooms not washing their hands when they left the room.

“Any time you’re cleaning anything having to do with C diff, you definitely have to use bleach so it’ll kill the spores. Alcohol gel and alcohol wipes don’t do it,” Wohlgezogen said. “But we had complaints from staff, patients, and families about using bleach. They didn’t like the strong smell, [and] it seemed to stain the clothes of the staff using it.”

Addressing the issue began with patient and staff education. In addition, nurses were put in charge of providing patients and families with any items they wanted or needed, such as coffee or snacks, and they were tasked with making sure that objects were cleaned appropriately before and after use.

Next, they realized the importance of patients bathing or showering daily to decrease the bacterial count on the body. Then, the team determined that bedside commodes likely were not being cleaned as thoroughly as they should be, particularly the heavy-duty bucket component that catches the waste. Therefore, City of Hope began to invest in single-use patient items.

“Once we [changed] the bedside commode buckets [to] single use, we definitely saw a decrease [in C diff],” Wohlgezogen said.

The team also ensured that there were enough vital sign monitors that one could be kept in the room of each oncology patient in isolation for the duration of their stay without needing to be shared with other patients. Similarly, they encouraged limiting movement of computer workstations on wheels among isolation patients’ rooms when possible.

“Our recommendation is to maintain a high focus on [C diff] infection prevention and [to continue] the education with the nursing [and medical] staff, patients’ families, and all the people who touch the patients,” Wohlgezogen said.

1. Wohlgezogen K. Decreasing C. difficile infection rates: the bundle approach. Presented at: 2020 Oncology Nursing Society Bridge virtual conference; September 8-17, 2020; Virtual. Accessed September 22, 2020.

Opioid Overview: Know What to Use and When

Patients with cancer can experience immense pain, and it is crucial that oncology nurses know how to effectively—and safely&mdash;manage that pain.

“Pain management is both an art and a science. You really have to see how the patient is doing. How are they tolerating the opioids?” said Jeannine Brant, PhD, APRN, AOCN, FAAN, an oncology clinical nurse specialist and the director and lead scientist of Collaborative Science and Innovation at Billings Clinic in Montana. Brant recently led a presentation on opioid use at the 2020 Oncology Nursing Society Bridge virtual conference, held September 8 to 17, 2020.

Brant said that morphine is “the gold standard for comparison for all opioids” because it is inexpensive and can be given orally or rectally, in immediate- or controlled-release form, and can even be injected into the space or fluid around the spinal cord.

Morphine has 2 metabolites (byproducts of the body breaking down the drug): morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Nurses should be aware that for patients with compromised kidney function, M3G and M6G accumulate in the body and can cause adverse events (AEs) such as neurotoxicity, nightmares, hallucinations, or oversedation.

This opioid is not completely off the table for patients with renal insufficiency, but clinicians should adjust the dose appropriately.

Oxycodone, which is primarily administered orally and is sometimes combined with acetaminophen, is another common and versatile opioid option for patients with cancer.

Frequently, patients who experience AEs from morphine will switch to oxycodone. However, clinicians should be cautious when combining oxycodone and acetaminophen.

“We have to be careful of [combining the drugs] because we should limit acetaminophen to even less than 4 [grams] a day. Oftentimes, the limits are lower,” Brant said. “So, many times, giving pure oxycodone [with] acetaminophen on the side is one of the best ways to control pain, even though [oxycodone] has an active metabolite.”

While oxycodone is efficacious and has a tolerable AE profile, nurses and other providers should also remember that it may pose a greater risk for substance use disorder compared with other opioid pain relievers.

Finally, fentanyl is a drug that has various pharmacokinetic properties, depending on how it is administered.

For example, a transdermal patch can take up to 12 hours to start working because the drug must penetrate and saturate the patient’s subcutaneous adipose tissue before entering the systemic circulation. “Then, it finally starts working 12 hours later and lasts about 72 hours,” Brant said. “For some patients, however, you have to apply it every 48 hours because they really drain that patch more quickly.” Nurses must remember that transdermal fentanyl’s analgesic effect will likely be delayed in patients who are obese because the drug must saturate a greater amount of adipose tissue.

Clinicians can also give fentanyl via the transmucosal route. That method has a quick onset of action of approximately 5 to 10 minutes, according to Brant, who explained that fentanyl is absorbed through a mucous membrane—in the patient’s mouth, for example. Intravenous fentanyl also takes effect quickly. ;

Clinical Insights: December 2020

Adverse Event Management for BRAF/MEK Inhibitors in Melanoma

With BRAF mutations occurring in approximately 50% of patients with cutaneous melanoma,1 the advent of BRAF/MEK inhibitors for this disease type has drastically improved outcomes in recent years, according to Grace Cherry, MSN, RN, NP, a nurse practitioner at the melanoma program at UCLA.

Cherry discussed recent exciting advancements in the melanoma field at the 4th Annual School of Nursing Oncology virtual meeting, held July 31 to August 1, 2020.2

“BRAF [V600] is a driver mutation,” Cherry said. ““It’s like that switch for that signal to have the cells grow is constantly on. It’s like a light has been switched on … When it’s switched on, there’s no stopping that signal. It’s continuing to allow those tumors to grow rapidly. So, when we give a BRAF/MEK inhibitor, it’s like turning off that switch.”

There are 3 FDA-approved BRAF/MEK inhibitor combinations (below). Although there is some overlap between their adverse events (AEs), such as fatigue and nausea, there are specific AEs frequently seen with each regimen that nurses need to be aware of when treating patients, according to Cherry.

• Dabrafenib (Tafinlar)/trametinib (Mekinist): fever

• Vemurafenib (Zelboraf)/cobimetinib (Cotellic): photosensitivity and rash

• Encorafenib (Braftovi)/binimetinib (Mektovi): nausea

“Nurses are our front line as far as giving these treatments and also in teaching our patients about side effects and detecting them,” Cherry said.

The first step in managing AEs from BRAF/MEK inhibition is confirming that the patient has a BRAF V600E or V600K mutation (which represent up to 90% and 10% of BRAF mutations in melanoma, respectively). “If [patients] get these drugs and they’re BRAF wild type [negative for a BRAF mutation], it can have a paradoxical effect and make the tumor grow.”

Patients should then undergo a dermatological examination and echocardiography because there is a small chance that they may have cardiotoxicity. If the patient is experiencing blurred vision, which is rare, they should be referred to an ophthalmologist to check for ocular toxicity.

All patients experiencing AEs from their BRAF/MEK inhibition treatment should undergo laboratory testing. Clinicians can monitor their blood for elevated liver enzymes, reduced white blood cell count, and markers of rare AEs, such as elevated creatine phosphokinase, which may indicate a rare AE, rhabdomyolysis. Cherry also noted that dose interruptions were very common in the clinical trials that led to approval of these drugs.

“If [patients are] having a really severe side effect, it’s warranted to do a dose reduction so they can continue taking it on a continuous basis. Sometimes they may have to discontinue if [toxicities] are really severe,” Cherry said.

Despite the landmark advances of BRAF/MEK inhibitors—as well as other agents, such as immunotherapy&mdash;in melanoma, there is still more work to be done.

“Our patients have come a long way compared [with] before BRAF/MEK inhibitors and immunotherapy came along, but we have a long way to go,” Cherry said. “Not everybody responds to [these agents], and we need to improve on them.”

1. Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol. 2018;31(1):24-38. doi:10.1038/modpathol.2017.104

2. Cherry, G. Melanoma: treatment updates in advanced melanoma. Presented at: 4th Annual School of Nursing Oncology; July 31-August 1, 2020; Virtual.

Managing Systemic Toxicities and Limiting Therapy Nonadherence in Breast Cancer

One of the most important tasks oncology nurses face is ensuring that patients are taking their medications consistently and correctly and that adverse events (AEs) are properly managed—especially in patients with breast cancer, according to Patricia Jakel, MN, RN, AOCN.

“[Nonadherence] is a nursing issue,” Jakel emphasized. “Learn that patients who think they’re taking their [medications] correctly [can still be mistaken]. … Try to help patients make sure that all medications, especially oral medications, are taken correctly. It really does have an impact on overall life expectancy.”

In her presentation on systemic toxicity management in breast cancer at the 4th Annual School of Nursing Oncology virtual meeting, held July 31 to August 1, 2020, Jakel, an advanced practice nurse with the University of California, Los Angeles (UCLA) Medical Center, Santa Monica, an associate professor of nursing at the UCLA School of Nursing, and a patient with breast cancer herself, discussed the best supportive care strategies that should accompany breast cancer therapy.

Medication adherence rates for patients with cancer range from 15% to 87%, with a mean of 50%. Poor adherence has been found to be associated with patient age older than 65 years, prescriptions written by nononcologists, polypharmacy, and high co-payments. Poor adherence to treatment regimens—whether due to AEs or confusion about how to take medications&mdash;can lead to worse patient outcomes, such as disease progression, development of resistance to certain medications, and even death.

A number of therapeutic agents are currently available for patients with estrogen receptor (ER)—positive breast cancer, including selective ER response modulators such as tamoxifen (Soltamox), toremifene (Fareston), and raloxifene (Evista); luteinizing hormone–releasing agents for ovarian suppression such as goserelin (Zoladex), leuprolide (Lupron), and triptorelin (Triptodur); aromatase inhibitors (AIs) such as anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara); and ER downregulators such as fulvestrant (Faslodex). AEs that accompany these endocrine therapies can lead to therapy nonadherence, according to Jakel. Aside from joint pain known AEs include hot flashes, menopausal symptoms, libido loss, blood clots, and osteoporosis and may contribute to a decrease in long-term adherence to oral endocrine therapies. This issue of nonadherence may affect between 30% and 80% of patients, especially those who have been receiving these therapies for at least 5 years.

“[One patient] stopped [her AI treatment] because of bone pain,” Jakel explained. “We tend to not think about that … but probably about 40% of patients have pretty severe bone pain that makes it hard to get up off the couch.”

Patients who receive CDK4/6 inhibitors also tend to experience AEs such as diarrhea, though this can be managed with other agents such as loperamide (Imodium) and octreotide (Sandostatin), which are likely to be effective. The benefits of agents such as amifostine (Ethyol) and neomycin (Neo-Rx) must be balanced against their possible harm. Jakel stated that encouraging patients with diarrhea to follow the BRAT diet— bananas, rice, applesauce, and toast&mdash;is another expert opinion worth exploring.

Fatigue is also a prevalent AE among patients undergoing breast cancer therapy. Though numerous medications exist to help manage fatigue, Jakel emphasized that exercise can help patients to feel better, coupled with proper sleep hygiene, such as decreasing screen time with electronic devices and reducing alcohol consumption.

Nausea is another gastrointestinal AE associated with CDK4/6 inhibitors that can be managed through recommended lifestyle changes. “What time of day should [patients] take [their CDK4/6 inhibitor]?” Jakel asked. “How should they take it? Should they take it with food? Should they take it before bed? Should they take it in the morning and [risk] being nauseated during the day? Have that conversation [with patients] because if it’s only once a day—though many drugs are twice a day&mdash;you can play around with the time of day [patients] take it to help with nausea.”

A large proportion (75%) of patients with breast cancer experience cognitive impairment, or “chemo brain,” which can lead to confusion and memory loss. Thus far, cognitive training has been shown to be an effective way to manage cognitive impairment. Other activities that help to focus the mind, such as yoga, meditation, and psychoeducational interventions may also help; however, their effectiveness has not yet been established.

Another AE that is not discussed enough, according to Jakel, is ongoing problems with sexual function—an issue that half of all cancer survivors report. Especially following antiestrogen breast cancer therapies, a large number of female patients report having low or absent sexual desire. Menopausal symptoms and dyspareunia (painful intercourse) due to vaginal dryness may be 2 contributing factors, as well as issues with body image after reconstructive surgery.

Clinical Insights: October 2020

Evaluating the benefits of the subQ vs IV formulation of the trastuzumab-pertuzumab combination for the management of HER2+ breast cancer and examining the potential use of at-home administration.

HER2-targeted Therapy: Routes of Administration

Nurse practitioners provide insight on issues surrounding the administration of dual HER2-targeted therapy in the neoadjuvant/adjuvant setting and counseling patients on common AEs associated with trastuzumab-pertuzumab for the treatment of HER2+ breast cancer.

Practical Management of Early Stage HER2+ Breast Cancer

Carfilzomib Triplet Regimen Is Not Superior To Standard of Care in Myeloma

The combination of next-generation proteasome inhibitor carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Decadron) (KRd) did not demonstrate superior progression-free survival (PFS) in newly diagnosed multiple myeloma (NDMM) compared with the current standard-of-care triplet of bortezomib (Velcade), lenalidomide, and dexamethasone (VRd), according to results of the ENDURANCE (E1A11) trial (NCT01863550) presented in a presscast ahead of the 2020 American Society of Clinical Oncology Virtual Scientific Program.1

In the VRd cohort, median PFS was 34.4 months compared with 34.6 months in the KRd arm. Moreover, there were no PFS differences based on age, t(4;14) status, or disease stage.

The randomized phase 3 trial also assessed whether indefinite maintenance with lenalidomide improved overall survival (OS) compared with 2-year maintenance. Data are not yet mature for this end point.For the maintenance phase, patients received lenalidomide at 15 mg on days 1 to 21 every 4 weeks.

Given previous phase 3 trial results showing superior efficacy of carfilzomib compared with bortezomib in the relapsed setting, investigators sought to determine whether carfilzomib could replace bortezomib in the current standard-of-care triplet induction regimen for patients with standard- and intermediate-risk NDMM.

Patients who were enrolled in the trial lacked high-risk features such as chromosome 17p deletion, translocation t(14;16) or t(14;20), plasma cell leukemia, a high-risk profile based on the GEP70 test of 70 genes associated with multiple myeloma aggressiveness. The median age of all patients was 65 years.

The 542 patients in the VRd arm received 12 cycles (3 weeks each) of bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 (days 1 and 8 for cycles 9-12); lenalidomide at 25 mg on days 1 to 14; and dexamethasone at 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12.

The 545 patients in the KRd arm received 9 cycles (4 weeks each) of carfilzomib at 36 mg/m2 on days 1, 2, 8, 9, 15, and 16; lenalidomide at 25 mg daily on days 1 to 21; and dexamethasone at 40 mg weekly.

The second of 3 planned interim analyses revealed that substituting carfilzomib for bortezomib did not affect PFS (HR, 1.04; 95% CI, 0.83-1.31; P = .74). Three-year OS rates were also similar in both arms, at 84% in the VRd arm (95% CI, 80%-88%) and 86% in the KRd arm (95% CI, 82%-89%).

In the VRd cohort, 57% of patients did not complete the induction treatment. The most common reasons for leaving the trial were pursuit of an alternative therapy (18%), adverse events (AEs; 17%), patient choice (7%), and disease progression (6%).

In the KRd arm, 39% of patients withdrew from treatment early due to pursuit of an alternative therapy (14%), AEs (10%), patient choice (4%), and disease progression (4%).

Overall, treatment-related AEs (TRAEs) of grade 3 or higher occurred in 59% of VRd and 66% of KRd patients. Nonhematologic TRAEs accounted for the majority, with rates of 41% and 48%, respectively. Although peripheral neuropathy was more common with VRd (53% compared with 24% in KRd; P < .001), the KRd arm experienced a significantly higher rate of cardiopulmonary and renal TRAEs (16% compared with 5% in the VRd arm; P < .001).

Based on these study results, investigators determined that VRd remains the superior triplet induction regimen in this patient population, making it a suitable backbone for 4-drug combinations as well.

Staff