CE lesson worth 1 contact hour that is intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for patients with cancer.
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.
Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may participate in this CE activity.
Upon completion, participants should be able to:
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
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®.
To assist in treating patients with immunerelated adverse events (irAEs), nurses can follow 5 pillars: prevent, anticipate, detect, treat, and monitor.1 “As [a] nurse in oncology, to help manage the toxicity profile that patients have, I really like the Champiat et al model, which [includes] 5 pillars of management of immunotherapy,” Marianne Davies, DNP, RN, CNS, ACNP-BC, AOCNP, who is an associate professor and oncology nurse practitioner at the Yale Comprehensive Cancer Center in New Haven, Connecticut, said during a presentation at the 3rd Annual School of Nursing Oncology™, hosted by Physicians’ Education Resource®, LLC, and held August 2-3, 2019, in San Diego, California. “It can help guide your practice.”
The first step in preventing irAEs involves evaluating patients for autoimmune risks before they start treatment. These risks include Addisons disease, celiac disease, Crohns disease, Graves disease, Hashimotos thyroiditis, multiple sclerosis, myasthenia gravis, pernicious anemia, rheumatoid arthritis, Sjogrens syndrome, systemic lupus erythematosus, type 1 diabetes, and ulcerative colitis. Also, nurses should know of any prior organ or hematopoietic stem cell transplantations to monitor the potential risk of graft rejection.
Nurses should also be prepared for medication reconciliation, including over-the-counter drugs and herbal supplements. “There are several levels of prevention, or preparing patients for treatment,” Davies said. “One of the key ones is that your institution needs to provide appropriate resources to help you manage your patients [who] are on therapy.” The next pillar is anticipation of irAEs through baseline assessments during and after treatment. These can include a review of systems, physical examinations, and laboratory evaluations such as a complete blood count, comprehensive metabolic panel, and thyroid panel. “How do we prevent toxicities for patients or prepare to best manage [them]? By understanding not only the mechanism of action of the checkpoint inhibitors but also how [to] manage each specific [toxicity],” Davies said. “Patients need to be encouraged and instructed to report any new symptoms because even subtle symptoms may be an immune-related toxicity, and that is really important for us to understand. [If] we can manage the toxicity [early], most often, patients can successfully continue on that therapy. We need to encourage and educate our patients [about] that.” DETECT Similar to anticipation, detection of irAEs is an area where both healthcare providers and patients play a role.
Healthcare providers should conduct regular monitoring of patients using standardized irAE assessment checklists, telephone triage, and toxicity management guidelines. In addition, nurses should be sure to always rule out any other cause of toxicity. Lastly, they should assess and monitor the kinetics of the toxicity. After following these steps, the healthcare team is responsible for determining the need for hospitalization or ambulatory care. Treatment with immunotherapy also requires patients to maintain close communication with their healthcare providers. They should report any new signs or symptoms they develop, as well as any visits to other healthcare providers or hospital admissions.
After an irAE is detected, the next pillar is treating the toxicity. Davies offered various sources that nurses can use for reference, including guidelines from the American Society of Clinical Oncology, the National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the AIM With Immunotherapy Foundation.
During and after treatment of irAEs, healthcare providers must continue to monitor the kinetics of the toxicity. Nurses should also monitor for resolution of the toxicity, complications of immunosuppressant drugs, and treatment response. “Communication is the essential thread,” Davies said, adding that the multidisciplinary team plays a key role in managing irAEs. “[Another] key [thing] we can do is helping to identify ‘IO champions’ within your facility [who] can be a resource as you are going through this.”
Davies M. Multidisciplinary Management of Immunotherapy-Related Adverse Events. Presented at: 3rd Annual School of Nursing Oncology; August 2-3, 2019; San Diego, CA.
With high incidence rates of breast cancer, nurses must stay up to date on the newest treatment options, according to Madelaine Kuiper, MSN, RN, OCN.1 “There is a lot going on at the moment,” said Kuiper, an oncology nurse practitioner at the University of California, Los Angeles Santa Monica Hematology/Oncology Breast Program, during a presentation at the 3rd Annual School of Nursing Oncology™, hosted by Physicians’ Education Resource®, LLC, and held August 2-3, 2019, in San Diego, California.
One of the most important changes in the past 2 years is in staging of the disease, with the addition of biomarkers, as well as tumor grade, which reflects the degree of proliferation. Incorporation of these molecular characteristics into the traditional anatomic TNM (tumor-node-metastasis) staging system has allowed the creation of a prognostic staging protocol. Anatomic staging of breast cancer consists of: Stage 0: (carcinoma in situ): Abnormal cells are present but have not spread to nearby tissue. Stage I (early stage): Cancer has spread to other tissue in a small area. Stage II (localized): Tumor is between 20 mm and 50 mm with some lymph nodes involved, or tumor is larger than 50 mm with no lymph nodes involved.
Stage III (regional spread): Tumor is larger than 50 mm, with more lymph nodes involved across a wider region. In some cases, no tumor is present at all. Cancer may have spread to skin or chest wall. Stage IV (distant spread): Cancer has spread beyond the breast to other parts of the body. CDK4/6 INHIBITORS Cyclin-dependent kinase (CDK) 4/6 inhibitors arrived in 2015 with palbociclib (Ibrance), then ribociclib (Kisqali) in 2017 and abemaciclib (Verzenio) in 2018 as first-line treatments for postmenopausal women with HR-positive/HER2negative metastatic breast cancer. The results from the first trial dedicated to evaluating endocrine therapy with and without a CDK4/6 inhibitor, the MONALEESA-7 study2, showed an overall survival (OS) benefit from the addition of ribociclib to endocrine therapy in premenopausal patients with advanced breast cancer.
On March 8, 2019, the FDA approved the antiPD-L1 drug atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) for women with PD-L1 positive locally advanced or metastatic triple-negative breast cancer. The agency also approved a companion diagnostic test, the VENTANA PD-L1 (SP142) Assay, which detects PD-L1 expression. Adverse events (AEs) associated with the atezolizumab/nab-paclitaxel combination include alopecia, peripheral neuropathy, fatigue, nausea, diarrhea, anemia, constipation, cough, headache, neutropenia, vomiting, and decreased appetite. Because atezolizumab affects the immune system, nurses must also be aware of AEs such as immune-mediated pneumonitis, hepatitis, colitis, and endocrinopathies; infections; and infusion-related reactions.
On May 24, 2019, the FDA approved the PI3K inhibitor alpelisib (Piqray) in combination with fulvestrant (Faslodex) for postmenopausal women and men with HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer. As with atezolizumab, the agency approved a companion diagnostic, the therascreen PIK3CA RGQ PCR Kit, to detect PIK3CA mutations in tissue and/or liquid biopsies. “The recommendation is to use the assay [with] a blood [sample]; if that is negative, then you send the patient’s tumor for testing,” Kuiper said.
She noted that despite this suggestion, the kit is not yet optimized for plasma samples, and she warned against using it to test blood at this time. The most common AEs associated with the combination include increased glucose, increased creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma glutamyl transferase, nausea, increased alanine amino transferase, fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, weight loss, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time, and alopecia. Hypersensitivity reactions and pneumonitis are 2 severe AEs nurses should watch for, and monitoring for drug interactions is key.
On October 16, 2018, the FDA approved the PARP inhibitor talazoparib (Talzenna) for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. Nurses should be aware of AEs such as fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and poor appetite. Warnings and precautions for talazoparib include myelodysplastic syndrome/acute myeloid leukemia and fetal harm.
REFERENCES 1.Kuiper M. Breast Cancer Essentials 2019. Presented at: 3rd Annual School of Nursing Oncology; August 2-3, 2019; San Diego, CA.
Patricia Jakel, MN, RN, AOCNUCLA Santa Monica Medical Center Solid Tumor Program Santa Monica, California
The most important components of supportive care are good symptom assessment and symptom management. That is going to look different for every person. For instance, we all know that exercise actually helps decrease fatigue; this is evidence-based. But that may not work for an 85-year-old patient who has been on breast cancer treatment for the last 10 years; you need an individualized care plan for such patients. Although the evidence suggests one course of action, you may have to take a somewhat different approach for specific patients. I think we are really good at symptom management. We are seeing some symptoms in patients with breast cancer that are different because of the class of drugs they are on. Monoclonal antibodies and kinase inhibitors work inside and outside the cell, so they can cause a variety of adverse events (AEs). But I think we have gotten really good at identifying and treating them.
What has helped nurses is education and opportunities. Not everyone can travel to a conference, but I think the availability of online education is crucial: There are videos you can watch and websites where you can receive continuing education on, for example, AEss associated with tyrosine kinase inhibitors or CDK4/6 inhibitors. These opportunities are really valuable. Journal articles are still great, but I think that, especially for future generations, digital communication is all about seeing things, touching things, and responding to things. Staying up-to-date is really important, and it is easier than ever.
Kristie L Khal
Nurses play a key role in addressing the barriers associated with clinical trial enrollment of patients with cancer, according to Maria Hendricks, MSN, RN.1 “One of the most important things is considerations for subject participation. That is why we all do what we do every day,” Hendricks, director of clinical research operations at the Abramson Cancer Center Clinical Research Unit at the University of Pennsylvania in Philadelphia, said during a presentation at the 3rd Annual School of Nursing Oncology™, hosted by Physicians’ Education Resource®, LLC, and held August 2-3, 2019, in San Diego, California.
The first barrier Hendricks mentioned: stringent eligibility criteria that may not be necessary for the endpoints of the study and could exclude some patients who would otherwise enroll. Similar to the difficulties faced by patients receiving standard care for cancer, financial hurdles and time constraints constitute a large barrier to clinical trial participation. “Not everything is paid for on the study, especially in cancer trials. That does sometimes get lost in translation,” she said, adding that although clinical trials do offer patients access to the latest available interventions, such access often comes with a cost.
Clinical trials can involve additional evaluations and more return visits than standard of care, Hendricks explained: “[Whether] someone is working or a stay-at-home mom, regardless of the scenario, time is of value, too.” Clinical trial access also poses a barrier, as does competition among trials to enroll patients with the same tumor type. Thus, nurses need to carefully pick which trials they pursue. Other barriers to trial participation include discrepancies in knowledge, education, and training; patient stress and fear; literacy and language barriers; and cultural issues. Although these areas of concern are not limited to cancer clinical trials, addressing them is important to ensure that patients are appropriately informed and aware of their options on an ongoing basis.
First, it is important to explain to patients the routine care costs incurred during a clinical trial. Some insurance plans will pay for these costs, whereas others will not; this varies by state and health insurance provider. Typically, Medicare covers routine costs. Hendricks explained that some insurance companies will pay for routine costs under the following circumstances: • The trial is medically necessary. • The costs are about the same as those of standard care. • There is no standard care for the patient’s disease. • The trial is funded by the National Cancer Institute (NCI). The prospective reimbursement analysis (PRA) process was created to help identify which parties are responsible for covering the costs of clinical trials. As part of clinical trial preparation, an institution’s billing compliance office reviews the study protocol with clinical staff to complete a PRA, determining routine costs according to Medicare coverage guidelines and estimating out-ofpocket costs for patients. “The key part [of a] PRA is being able to identify and work with the supporting group—whether it is an industry sponsor, National Institutes of Health partner, or philanthropic fund—to determine if elements will be covered,” Hendricks said, adding that nurses should be aware of this crucial piece of the puzzle. “When you have a patient [who] is on a trial, I encourage you to participate in the collaborative care of that patient,” she said. “When patients have a ton [of questions] and are thinking, ‘Hey, am I supposed to be charged for this?’ there are people [who can answer] these questions. It is important to reference your research team; they will help support you.”
To enhance patient access to clinical trials and identify more referral options, Hendricks said, nurses should use resources such as NCI-designated Cancer Centers and the NCI Community Oncology Research Program, which have been essential in providing access and funding, especially in underserved and minority communities throughout the United States. In addition, the Commission on Cancer program of the American College of Surgeons offers an accreditation program for high-quality cancer centers, providing important guidance to patients seeking cancer care. “There is a minimum [percentage of] accrual to trials that your institution needs to meet, [which is based on] your total number of new diagnoses and cancer patients,” Hendricks said. “Because of that, it is really important to identify which trials best match your patient population to ensure you have the available therapy options for your patients, as well as the right portfolio to [use] resources to enhance your accrual opportunities.”
1.Hendricks M. Clinical Trial Essentials 2019. Presented at: 3rd Annual School of Nursing Oncology; August 2-3, 2019; San Diego, CA.
Kristie L. Kahl
While the treatment landscape for lung cancer continues to grow, nurses must stay up-to-date on advances. Beth Eaby-Sandy, MSN, CRNP, a thoracic oncology nurse practitioner at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, discussed the various treatment options for patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).1 LOCALLY ADVANCED STAGE III NSCLC Durvalumab (Imfinzi) was approved as the first immunotherapy option for these patients. In a phase III trial of patients who had undergone chemotherapy/radiation, treatment with durvalumab demonstrated superior progression-free-survival (PFS) and overall survival (OS) compared with placebo.2 More recently, pembrolizumab (Keytruda) was also approved for patients with locally advanced NSCLC in April 2019; however, Eaby-Sandy noted that the patients in the drug trial received treatment intended for more advanced disease.
Nivolumab (Opdivo), pembrolizumab, and atezolizumab (Tecentriq) are approved for various indications in metastatic NSCLC. In the open-label, phase III KEYNOTE-024 trial, investigators evaluated pembrolizumab versus platinum-based chemotherapy. This study was the first to find that a single-agent immunotherapy was superior to platinum-based chemotherapy. The agent was also generally less toxic than chemotherapy. Next, investigators evaluated chemotherapy plus pembrolizumab compared with chemotherapy alone in the KEYNOTE-189 trial. At 12 months, 69% of patients were alive in the combination arm compared with 49% in the chemotherapy arm. Based on this success, investigators then evaluated a regimen of atezolizumab, carboplatin, paclitaxel, and bevacizumab (Avastin) in the IMpower150 trial. The regimen was associated with superior OS compared with carboplatin, paclitaxel, and bevacizumab (19.2 months vs 14.7 months; P = .02). Eaby-Sandy said this drug combination is typically used in patients with specific genetic mutations who require treatment with targeted therapies. “This can be a very toxic [regimen],” she said.
Chemotherapeutic approaches for these patients rely on platinum-based drugs. In the KEYNOTE-407 trial, investigators added pembrolizumab to carboplatin plus paclitaxel or nab-paclitaxel, improving PFS and OS. In the second-line setting, the National Comprehensive Cancer Network recommends the following treatments if not used in the frontline setting: docetaxel with or without ramucirumab (Cyramza); nivolumab, pembrolizumab, or atezolizumab; and gemcitabine.
To treat patients with EGFR-mutant NSCLC, erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), osimertinib (Tagrisso), and dacomitinib (Vizimpro) are used. However, osimertinib is the preferred option based on the FLAURA trial, which evaluated the use of osimertinib versus erlotinib or gefitinib in the first-line setting. The results showed an improved PFS of 18.9 months compared with 10.2 months, respectively (HR, 0.46; 95% CI, 0.37-0.57; P <.0001). For patients with ALK-positive NSCLC, crizotinib (Xalkori), ceritinib (Zykadia), alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena) are approved treatments.
Alectinib is the preferred treatment, Eaby-Sandy said. In a trial comparing alectinib to crizotinib, alectinib demonstrated a significant improvement in PFS, with some improvement in OS. There was also a significant improvement in intracranial response, and the agent was well tolerated. NSCLC positive for ROS1 mutations is effectively treated with crizotinib, the only approved therapy for these patients. However, lorlatinib, entrectinib, repotrectinib (TPX-0005), and the combined use of ceritinib and trametinib (Mekinist) are all under clinical investigation. For patients with BRAF mutations, dabrafenib (Tafinlar) plus trametinib is approved for the firstline setting based on phase II trial results. SCLC Due to the aggressive nature of SCLC, chemotherapy should be started immediately. Etoposide and platinum have been the mainstay; however, immunotherapy may now have a role.
In the phase I/III IMpower133 trial, investigators evaluated frontline atezolizumab plus carboplatin and etoposide in patients with early-stage disease. The immunotherapy regimen was superior to placebo plus chemotherapy in terms of 12-month OS (51.7% vs 38.2%, respectively). Also, median OS was 12.3 months compared with 10.3 months in the immunotherapy group (HR, 0.70; 95% CI, 0.54-0.91; P = .0069). In the past 12 months, nivolumab, pembrolizumab, and atezolizumab have all been approved to treat patients with SCLC.
1. Eaby-Sandy B. Lung Cancer: Essentials for Oncology Nurses. Presented at: 3rd Annual School of Nursing Oncology; August 2-3, 2019; San Diego, CA.
Brianna Kirkland, RN, CHPNUCLA Department of OB/GYN
If you are a specialist in lung cancer, it is very important that you remain up-to-date and know everything there is to know about treatments. Patients lose hope if they have someone who is not knowledgeable in front of them, and that is the last thing we want as healthcare providers. I believe that communication is one of the biggest keys to not only the success of the patient but also the entire quality of care. Lung cancer care involves a lot of communication.
At first, a lot of information is given at diagnosis time. Then you need to communicate some more, especially whenever there has been a setback. Nurses need to over-communicate and thoroughly explain to the patient what is going on. You need to be very careful to not make assumptions. Never assume that the patient necessarily understands what is going on or that you know how the patient is feeling or what they are going through.
One of the most important things any nurse should bear in mind, whether they are dealing with lung cancer or another condition, is to never forget that there is a person in front of you. Do not ever think for 1 second that they cannot determine what they want with the right education and the right tools around them. Never underestimate the importance of supportive care early on. A good palliative care program can really make a difference, not only in the patient’s life but also for their loved ones.
Kristie L. Kahl
All nurses—whether treating solid tumors or hematologic malignancies—should better understand blood cancers, such as chronic lymphocytic leukemia (CLL), as well as the treatment options and special considerations associated with the disease, said Laura J. Zitella, MS, RN, ACNP-BC, AOCN. “Many of your patients, even those with solid tumors, are at risk for developing leukemia. You might have a patient who has head and neck cancer but is being treated for CLL. So, [learning about leukemia] is applicable to [all nurses]. In addition, age is one of the biggest risk factors for leukemia,” Zitella, a hematology/oncology nurse practitioner and associate professor at the University of California San Francisco, said during a presentation at the 3rd Annual School of Nursing Oncology™, hosted by Physicians’ Education Resource®,LLC, and held August 2-3, 2019, in San Diego, California.1
CLL, one of the most common adult leukemias, is typically diagnosed by routine examinations or blood tests that find an asymptomatic increase in lymphocyte count. The disease is characterized by the proliferation of small, mature-appearing lymphocytes in the blood, marrow, and lymphoid tissues. Of note, more than 95% of cases in the United States are B-cell CLL, Zitella said. Clinical features of the disease include an absolute lymphocyte count >5000/mcL with a predominance of mature small lymphocytes, anemia and thrombocytopenia, lymphadenopathy, hepatosplenomegaly, hypogammaglobulinemia, and elevated beta-2 microglobulin and lactate dehydrogenase.
Approximately 80% to 90% of patients are asymptomatic at time of diagnosis. For these patients, the standard of care is simply observation. “There has been no survival benefit to early treatment [compared with watching and waiting] in asymptomatic patients,” Zitella explained. Treatment comes into play when patients could be eligible for a clinical trial; if they experience significant disease-related symptoms, such as fatigue, night sweats, weight loss, or fever without infection; if there is a risk of end-organ damage; if there is bulky disease (spleen >6 cm below costal margin or lymph nodes >10 cm); if the lymphocyte doubling time is ≤6 months; if there are progressive cytopenias; or if there is progressive high-risk disease.
Treatment for patients with CLL varies, depending on their age and the presence of any comorbidities or 17p deletion. “The most important thing in leukemias is knowing the genomic factors,” Zitella said. “This [had] been true for years before it became important in solid tumors. Genetic factors have always been the defining characteristic of leukemias.” For patients who are young (aged <65 years) and fit, preferred options for initial therapy are ibrutinib (Imbruvica) or a clinical trial. Therapies in the relapsed setting include ibrutinib (if not used in the front-line setting); venetoclax (Venclexta) plus rituximab (Rituxan); duvelisib (Copiktra); or idelalisib (Zydelig) plus rituximab.
For young patients with comorbidities, those aged 65 or older, and individuals who are frail with significant comorbidities, oncologists use ibrutinib or venetoclax plus obinutuzumab (Gazyva) in the first-line setting, or they suggest a clinical trial. Patients in this group who have relapsed may be treated with ibrutinib; venetoclax plus rituximab; duvelisib; or idelalisib plus rituximab. For patients with a 17p deletion, initial therapy consists of either ibrutinib, venetoclax plus obinutuzumab, or a clinical trial. In the relapsed setting, treatment includes ibrutinib (if not used in the front-line setting); venetoclax plus rituximab; duvelisib; or idelalisib plus rituximab. “There is a trend in leukemia toward moving toward nonchemotherapy-based regimens,” Zitella said. “In CLL, all of the current preferred regimens recommended by the NCCN [National Comprehensive Cancer Network] are nonchemotherapy; that has been a really exciting advance.”
With any treatment, nurses should be aware of the risk of a variety of adverse events (AEs). AEs associated with ibrutinib include diarrhea, hypertension, atrial fibrillation, bleeding, and rash. Hypersensitivity reactions and hepatitis B reactivation are commonly associated with both obinutuzumab and rituximab. Nurses should take precautions against tumor lysis syndrome when administering venetoclax.
Lastly, duvelisib and idelalisib are both associated with diarrhea, hepatotoxicity, pneumonitis, rash, and cytomegalovirus reactivation; pneumocystis pneumonia prophylaxis should also be administered. In addition, nurses should monitor for atypical infections, such as sinopulmonary infections; hypogammaglobulinemia; autoimmune hemolytic anemia and/or autoimmune thrombocytopenia; and non-melanomatous skin cancer. Zitella recommended that nurses reference the NCCN guidelines to better understand various leukemias, their treatments, and their AEs. She shared an additional tip with the audience: “The NCCN patient guidelines [are] an excellent summary about any disease that is very easy to read,” she said. “When I am seeing something for the first time, that is one of the things that I use.”
Zitella L. Chronic Lymphocytic Leukemia: Essentials for Oncology Nurses. Presented at: 3rd Annual School of Nursing Oncology; August 2-3, 2019; San Diego, CA.