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Clinical Insights: October 2020

Thursday, October 22, 2020

Release Date: October 22, 2020
Expiration Date: October 22, 2021


This activity is provided free of charge.

STATEMENT OF NEED

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.

TARGET AUDIENCE

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

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.
 
DISCLOSURES/RESOLUTION OF COI

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.

METHOD OF PARTICIPATION
  1. Read the articles in this section in its entirety.
  2. Go to  www.gotoper.com/go/October 
  3. Complete and submit the CE posttest and activity evaluation.
  4. Print your CE Certificate.
OFF-LABEL DISCLOSURE/DISCLAIMER

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®.

Melanoma

Adverse Event Management for BRAF/MEK Inhibitors in Melanoma

By Brielle Benyon

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—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.”

References

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.
 

Breast Cancer

Managing Systemic Toxicities and Limiting Therapy Nonadherence in Breast Cancer

By Hayley Virgil

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—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—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—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.

Male patients with breast cancer can also experience sexual AEs. Over half (54%) of men who had received antiandrogen therapy reported no sexual desire following a year of treatment. Additionally, 80% to 90% of patients developed difficulties with erectile function. “We need have to this conversation about reproductive health,” Jakel said

There are a handful of models in the space to help make these conversations around sexual health easier. The PLISSIT model describes increasingly complex levels of intervention: Give the patient permission to discuss the topic, provide limited information about issues of concern, offer specific suggestions, and refer the patient to a specialist for intensive therapy.

There is also the BETTER model, another effective model, involving bringing up the topic of sexual health, explaining that sex is an important part of quality of life, telling the patient about resources, explaining that resources are available even if the timing is not right, providing education about any sexual AEs that may occur during treatment, and maintaining a record in the patient’s chart to document that the topic has been discussed.

Even with education and patient understanding, AEs still contribute to the breakdown of medication adherence among patients with cancer. Even if the patient appears to understand their treatment regimen, it is important to anticipate that there will be some degree of confusion, Jakel explained. With many systemic cancer therapies given orally, it is important to ensure that patients are adhering to regimens outside the clinic. “Interview patients, and don’t forget to do a medication reconciliation” she concluded. “[Ask patients], ‘How are you taking your medications at home?’ You can do pill counts, [and] pharmacies are much more involved than they used to be, so rely on your [pharmacists]. You can look at disease response rates and ask [your patient] if they’re taking their medication.”

Reference
Jakel P. Breast cancer: systemic toxicity management. Presented at: 4th Annual School of Nursing Oncology; July 31-August 1, 2020; Virtual. Accessed July 31, 2020. Nurse Perspective

Madelaine Kuiper, MSN, RN
UCLA Health


I do chemo teaching with my patients whenever I start new therapy. When someone's new and they're very overwhelmed, they don't hear so much data. We also try to be consistent and not confuse the patient. So, [we are often coming] up with standardized ways of trying to address symptom management and try to be consistent when it comes to oral therapies.

If they're coming in to see the infusion nurses, they're also checking where are they at in their regimen. So again, we're getting this double check on compliance, but also [asking if patients are] taking [medications] correctly.

Lots of eyes always make things [better for monitoring patients]. Unfortunately, some clinics might not have [the staff] to do all of this teaching that the nurses are involved in, but the resources that I'm so happy to see now that a lot of the drug companies are producing and having available when they bring out these new drugs to actually make it easier for patients to be compliant and for the nurses to teach as well, which is a great thing. .

 

Cervical Cancer

Cervical Cancer: Symptoms, Treatment, and Outlook

By Brielle Benyon

Although cervical cancer rates are expected to decline thanks to the human papilloma virus (HPV) vaccine, certain groups still have a higher incidence of the disease, and it is crucial for nurses to know the signs of cervical cancer as well as the treatment modalities once someone is diagnosed.

“The key risk factor for cervical cancer is HPV,” Carolyn Grande, MSN, CRNP, AOCNP, a medical oncology nurse practitioner at the Abramson Cancer Center, Hospital of the University of Pennsylvania in Philadelphia, said in a presentation at the 4th Annual School of Nursing Oncology virtual meeting, held July 31 to August 1, 2020.

Risk Factors and Symptoms

“For most people, the body can clear HPV, but it can be chronic for others—especially those who have higher risk,” Grande explained.

She noted that cervical cancer risk factors are similar to the risk factors for sexually transmitted diseases. They include the following:

• HPV infection
• History of smoking
• Engaging in intercourse at an early age (<18 years)
• Larger number of sexual partners (>5) and exposure to sexually transmitted diseases
• Lower socioeconomic status
• Long-term use of oral contraceptives (>5 years)

Although most annual cancer screening starts at an older age, the American Cancer Society recommends yearly cervical cancer screening to start at age 25, with HPV testing every 5 years.

And though the disease often starts off as asymptomatic, patients may develop symptoms once the tumor grows larger. These can include bleeding after intercourse, between periods, or after menopause and pelvic pain during intercourse. Symptoms of more advanced-stage disease may include swelling of the legs, hematuria, and problems moving the bowels or urinating.

Cervical Cancer Treatment

Because cervical cancer usually has no early symptoms, it is often diagnosed at later stages, when it is typically treated with radiation and/or chemotherapy.

“In terms of cancer treatment in advanced disease, you will have primary chemoradiation. The volume of radiation would be guided by the amount of nodal involvement. In the absence of nodal disease, pelvic external beam radiation therapy [EBRT] with concurrent platinum-containing systemic therapies and brachytherapy can be options,” Grande said.

Cervical cancer with positive para-aortic and pelvic lymph nodes is often treated with extended-field EBRT, brachytherapy, and concurrent platinum-containing chemotherapy.

Metastatic disease, which is unfortunately rarely curable, is usually treated with platinum-containing chemotherapy and palliative EBRT.

As treatments evolve and more people receive the HPV vaccine, cervical cancer statistics are predicted to trend in the right direction.

“Globally, [cervical cancer] is the fourth most common cancer-related [cause of] death in women. The good news, however, is that the incidence is expected to decline in women who received the HPV vaccine,” Grande said.

Reference

Grande C. Gynecologic cancer: essentials for oncology nurses. Presented at: 4th Annual School of Nursing Oncology; July 31-August 1, 2020; Virtual. Accessed August 1, 2020.
 
Blood Cancers

CAR T-Cell Therapy: Promising But Not Perfect


By Brielle Benyon

The advent of chimeric antigen receptor (CAR) T-cell therapy is a “game changer for blood cancers,” according to Kelly Garvin, MA, BSN, RN. However, these treatments may lead to potentially lethal adverse events (AEs), highlighting the importance of specific training and education for nurses who care for patients undergoing this type of therapy.

“CAR T-cell therapy is powerful, with impressive success rates, but also with specific dangerous [adverse events] that require trained nursing staff to manage,” Garvin, a nurse in the Department of Malignant Hematology at H. Lee Moffitt Cancer Center in Tampa, Florida, said in a presentation at the 4th Annual School of Nursing Oncology virtual meeting, held July 31 to August 1, 2020.

How CAR T-Cell Therapy Works

There are currently 3 FDA-approved CAR T-cell therapies, all indicated for patients with relapsed or refractory B-cell malignancies. They are axicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), and tisagenlecleucel (Kymriah).

To create CAR T cells, a clinician extracts T cells from the patient’s blood via apheresis and sends them to a specialized laboratory. There, the cells are programmed to recognize and attack malignant B cells in the blood through the addition of a receptor that targets the B-cell–specific antigen DC.1. The laboratory process can take 10 to 14 days, according to Garvin.

“While B cells develop a very specialized affinity for specific antigens, T cells are more like professional mercenaries that go after the bad guys. And sometimes, cancer cells develop ways of hiding from the immune system, escaping that surveillance,” Garvin said. “But with CAR T-cell therapy, we’re combining the specificity and the affinity of a B cell with the cytotoxic fighting ability of a T cell.”

After receiving lymphodepleting chemotherapy, the patient is infused with the reengineered T cells. Then, they typically stay in the hospital for 2 weeks or longer, Garvin explained. During this time, it is crucial for nurses to monitor for major AEs, namely, cytokine release syndrome (CRS) and neurotoxicity.

“These can occur quickly while the patient is still an inpatient and you’re taking care of them. They occur commonly, and they can be deadly,” Garvin said, adding that most patients who receive CAR T-cell therapy will experience 1 or both of these AEs.

Cytokine Release Syndrome

CRS commonly occurs approximately 2 to 3 days after a CAR T-cell infusion but can happen as early as a few hours after. This AE is marked by the release of high levels of inflammatory cytokines, a type of immune molecule, into the bloodstream. Signs of CRS include fever, chills, and rapid heart rate.

“We take vital signs at least every 4 hours on the floor and more often if we feel like something is brewing,” Garvin said. She noted that initial signs of CRS include fever, chills, and rapid heart rate. “And then after that, you can see hypoxia and hypotension. [We also] monitor [laboratory blood tests] every day.”

Severe or life-threatening CRS is treated with tocilizumab (Actemra); if that does not work, steroids may also be used.

Neurotoxicity

Neurotoxicity can manifest as any number of nervous system–associated symptoms, including delirium, dysphasia, word searching, encephalopathy, and seizure. The first sign is often a headache, and nurses should also watch for a “blank look” in patients’ eyes, Garvin said.

Garvin told a story about realizing that a patient, whom she had been treating for 2 weeks, was experiencing neurotoxicity. “I walked into [her room] one morning, and I handed her her pill cup, and she just stared at it like she’d never seen it before,” Garvin said. “She didn’t answer any of my questions; she didn’t look at me, and then she poured her pills down her shirt. This was the first sign that that some [neurotoxicity] was beginning to brew.”

Risk factors for neurotoxicity, the typical onset of which is approximately 4 to 6 days after CAR T-cell infusion, include higher disease burden and concurrent CRS.

Treatment for neurotoxicity is often supportive care, and steroids may be administered if needed. Garvin explained that treatment guidelines exist for both neurotoxicity and CRS, depending on the specific type of CAR T-cell therapy the patient is receiving.

CAR T-cell therapy has transformed the treatment of some hematologic cancers, but—like every other therapy—it is not perfect and comes with risks.

“We do see relapses after treatment, we see death from [adverse events],” Garvin said. “I don’t want to oversell the treatment, but what I saw is that this treatment offers the promise of hope to patients for whom traditional chemotherapy didn’t work and their prognosis was very poor.”

Reference

Garvin, KL. CAR-T therapy: nursing considerations. Presented at: 4th Annual School of Nursing Oncology; July 31-August 1, 2020; Virtual.

 
Lung Cancer

Durvalumab Boosts Survival Outcomes in Locally Advanced NSCLC


By Brielle Benyon

Non–small cell lung cancer (NSCLC) is often diagnosed at later stages because there are few signs indicative of cancer when the disease first appears. By the time NSCLC becomes locally advanced—meaning it has spread to the mediastinal lymph nodes in the center of the chest—patients may start to experience symptoms, leading to their diagnosis, according to Beth Sandy, MSN, CRNP.

“Once those lymph nodes get big … you start to have symptoms like shortness of breath,” Sandy, a thoracic oncology nurse practitioner at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, said. She recently discussed treatment for locally advanced NSCLC at the 4th Annual School of Nursing Oncology virtual meeting, held July 31 to August 1, 2020.1

Experts debate whether it is appropriate to conduct surgery on stage III locally advanced NSCLC, according to Sandy, who noted that there is no consensus on whether surgery or concurrent chemoradiation is superior in terms of survival and adverse events.

Up-front Chemoradiation

Sandy outlined 3 common chemotherapy regimens given with radiation:

• Paclitaxel plus carboplatin; a low dose given once a week
• Pemetrexed plus either carboplatin or cisplatin; a full dose given every 3 weeks
• Etoposide plus cisplatin; etoposide given on days 1 through 5 and cisplatin given on days 1 and 8, repeating every 28 days
“Paclitaxel and carboplatin is probably the most common [regimen]. It’s the easiest to tolerate,” she said. “With pemetrexed and platinum (either cisplatin or carboplatin), the good thing about that regimen is that it’s full dose … but it can be more toxic. Then, etoposide/cisplatin is kind of a middle-of-the-road dose.”

After chemoradiation, patients with locally advanced NSCLC traditionally received no further treatment because no other efficacious agents were available. However, development of the immunotherapy agent durvalumab (Imfinzi) has transformed treatment options for this population.

Immunotherapy With Durvalumab

Findings from the randomized, phase 3 PACIFIC trial (NCT02125461) showed that durvalumab improved outcomes in patients with stage III, locally advanced, unresectable NSCLC who had not progressed after 2 or more cycles of platinum-based chemotherapy plus radiation.2

Durvalumab bested placebo in terms of median PFS (16.8 months versus 5.6 months, respectively; HR, 0.52; 95% CI, 0.42-0.65; P < .001), as well as 12-month (55.9% versus 35.3%) and 18-month PFS (44.2% versus 27.0%).

The immunotherapy agent was also superior to placebo in terms of overall survival (OS). At the 36-month mark, 57.0% of participants in the durvalumab arm were alive compared with 43.5% in the placebo arm, and the median OS was not reached versus 29.1 months (HR, 0.69; 95% CI, 0.55-0.86).

“You can see that there is a significantly [larger] number of patients alive at the 3-year mark. This is really exciting,” Sandy said. “Once we get to that 5-year overall survival, we can then see if they’ve never relapsed … our cure rates may be improving.”

References

1. Sandy B. Lung cancer: essentials for oncology nurses. Presented at: 4th Annual School of Nursing Oncology; July 31-August 1, 2020; Virtual.
2. A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non-small cell lung cancer (PACIFIC). ClinicalTrials.gov. Updated March 19, 2020. https://clinicaltrials.gov/ct2/show/NCT02125461

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