|The following article features coverage from the 2022 Oncology Nurse Advisor Summit. Click here to read more of Oncology Nurse Advisor‘s conference coverage.|
Urologic cancers affect thousands of patients within the United States every year and treatment options have changed drastically with the adaptation of targeted therapy, immuno-oncology, antibody-drug conjugates, and combination therapy. During a session at the 2022 Oncology Nurse Advisor Summit Mary W. Dunn, MSN, RN, OCN®, NP-C, of the University of North Carolina in Chapel Hill, reviewed guideline-directed therapies for advanced bladder cancer and advanced renal cell carcinoma (RCC) and discussed the need for a collaborative interdisciplinary approach when addressing adverse events in these patient populations.
The principles of systemic therapy for advanced bladder cancer take into consideration a number of factors, including patient age, performance status, comorbidities, prior therapies, renal function (particularly for platinum-based chemotherapy eligibility), and disease stage.
Cisplatin-based chemotherapy is the preferred regimen in first-line metastatic bladder cancer for those who have never received a prior cisplatin treatment or have not received one within 12 months since cisplatin-based neoadjuvant chemotherapy, Dunn explained. The National Comprehensive Cancer Network (NCCN) guidelines recommend either gemcitabine + cisplatin with avelumab maintenance or dose dense methotrexate + vinblastine + doxorubicin + cisplatin with avelumab maintenance as first-line therapy for cisplatin-eligible patients with metastatic disease. For patients with advanced bladder cancer who are cisplatin ineligible, gemcitabine + carboplatin with avelumab maintenance; atezolizumab (for patients with PD-L1+ tumors or patients who are not eligible for platinum-based therapy regardless of PD-L1 status); or pembrolizumab are the preferred regimens for first-line treatment.
The NCCN guidelines have also been recently updated in regards to second-line therapy in advanced bladder cancer, Dunn explained, with pembrolizumab, nivolumab, avelumab, erdafitinib, and enfortumab vedotin being recommended post-platinum chemotherapy. After a checkpoint inhibitor, the guidelines recommend gemcitabine + cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in cisplatin-eligible, chemotherapy naive patients. For patients who are cisplatin-ineligible and chemotherapy naive, enfortumab vedotin or gemcitabine + carboplatin are recommended.
For third-line therapy, NCCN guidelines outline enfortumab vedotin and erdafitinib as preferred regimens.
“There’s challenges galore in all that we do for oncology… not all patients benefit from chemotherapy and not all patients benefit from immunotherapy,” Dunn said. “It’s incredibly difficult to predict outcomes, [which makes] treatment selection and treatment sequencing complicated.” Dunn stressed the importance of thinking about patient comorbidities and their risk status when navigating this complicated series of decision making.
With the emergence of new treatment options, clinicians must also be mindful of the potential adverse events. For immune checkpoint inhibitors, which is unique compared with platinum-containing chemotherapy, these drugs tend to be better tolerated and associated with a lower incidence of treatment discontinuation. The more common immune-related adverse events include maculopapular rash with or without pruritus, diarrhea, abdominal pain, colitis, hepatic events, asymptomatic elevation in amylase/lipase, headaches, visual disturbances, and fatigue.
For antibody-drug conjugates, the most common adverse events include rash, increased aspartate aminotransferase, hyperglycemia, increased creatinine, fatigue, peripheral neuropathy, ocular disorders, pneumonitis, neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, and abdominal pain. The most common severe adverse events include Stevens-Johnson syndrome, toxic epidermal necrolysis, hyperglycemia, peripheral neuropathy, diarrhea, hypersensitivity reactions, and nausea and vomiting.
No matter what therapy is being administered, Dunn stressed the need to inform patients to communicate with the oncology care team about any changes to their “norm” to ensure that these events are promptly identified and addressed.
In patients who receive erdafitinib, Dunn recommends that patients received monthly eye exams and to withhold treatment in patients who experience central serous retinopathy/retinal pigment epithelial detachment. Dose reduction should occur if hyperphosphatemia is detected.
Several guidelines outline best practice for monitoring patients receiving immune checkpoint inhibitors, how to detect the early signs of these adverse events, and how to manage the events. In general, collaborative management and referring to subspecialists as needed is very important.
For patients with RCC, there have been a large amount of drug approvals over the last 3 decades with exciting emerging data that are helping patients with this advanced disease to live longer.
NCCN guideline recommendations for advanced kidney cancer with clear cell histology are based on risk category, as determined by a number of risk calculators. For patients with favorable risk, the NCCN preferred guidelines include axitinib + pembrolizumab, cabozantinib + nivolumab, and lenvatinib + pembrolizumab. For patients with poor/intermediate risk the recommended therapies are axitinib + pembrolizumab, cabozantinib + nivolumab, ipilimumab + nivolumab, lenvatinib + pembrolizumab, or cabozantinib. Preferred subsequent lines of therapy include cabozantinib, lenvatinib + everolimus, and nivolumab.
“Sequencing wasn’t complicated prior to immunotherapy and combination therapy,” Dunn explained. “Now, it’s a blessing and a curse, we have so many options that are helping patients live longer but not really any good data regarding sequencing.”
In patients who are receiving an immune checkpoint inhibitor and targeted therapy regimens for their advanced RCC, patients and providers should be aware of the possibility of adverse events, including hypertension, hand foot syndrome, proteinuria, stomatitis, cytopenia, diarrhea, thyroid disorders, rash, transaminitis, hypophysitis/adrenal crisis pruritus, and pneumonitis. Whereas immune-related adverse events are managed using immunosuppressants, such as systemic corticosteroids, toxicities from antiangiogenic agents are managed primarily with treatment interruptions and dose reductions.
Treating RCC with combination immunotherapy can result in a variety of skin, hepatic, gastrointestinal, renal, eye, endocrine, pulmonary, and neurologic adverse events. “The diarrhea and hepatotoxicity profile of this combination tends to be high.” Dunn recommended monitoring for blood in the stool, changes to baseline bowel habits, and determine whether patient’s therapy needs to be paused.
In patients who receive targeted therapy, hypertension, proteinuria, wound healing, fatigue, hand-foot skin reaction, mucositis, hypothyroidism, rash, dysphonia, and LV dysfunction are some of the potential adverse events associated with therapy.
Similar to management of AEs in bladder cancer, Dunn stressed that collaborative management of adverse events in RCC is key. Patient and caregiver education is very important to ensure timely reporting of symptoms. It is also important to discuss goals of care with patients, as the therapies for these patients are unlikely to lead to cure, so balancing quality of life with goals of care is important in this patient population.
With new and emerging therapeutic options for patients with urologic cancers there are many benefits to patients, however challenges for providers and patients have emerged as well, particularly in regards to sequencing decisions and managing adverse events. “Nursing recognition and management is crucial as is patient and caregiver education,” Dunn concluded.
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Dunn MW. Updates in the Management of Urologic Cancers. Oral presentation at: 2022 Oncology Nurse Advisor Summit; March 25-27, 2022.