Lindsay Fischer is the Associate Editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

Following data from a 22-month extended follow-up, the FDA has granted capmatinib (Tabrecta) full approval for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors harbor a 

 exon 14 skipping, as detected by an FDA-approved test.

 on the same indication based on initial overall and duration of response (DOR) rates observed in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multi-cohort study. Patients with metastatic disease (n = 160) and a mutation leading to 

 exon skipping received 400 mg of oral capmatinib twice daily until disease progression or unacceptable toxicity.

Data supporting the 2020 accelerated approval included the overall response rate (ORR), which was 68% (95% CI, 55%-80%) among the treatment-naïve subgroup (n = 60) and 44% (95% CI, 34%-54%) in the pretreated group (n = 100). The DOR was 16.6 months (95% CI, 8.4-22.1) and 9.7 months (95% CI, 5.6-13), respectively.

The recommended dose for capmatinib is 400 mg orally twice daily with or without food. Patients should be instructed to swallow the tablets whole.

 They should not be broken, crushed, or chewed. If a patient misses or vomits a dose, they should not attempt to make up the dose, but instead wait and take the next dose at the scheduled time.

In the event of adverse reactions, providers should reduce the dose to 300 mg twice daily. At second adverse event (AE), the dose should be further reduced to 200 mg twice daily. Patients who are unable to tolerate 200 mg twice daily should permanently discontinue the drug.

The drug comes with warnings for interstitial lung disease (ILD) and pneumonitis, hepatotoxicity, and pancreatic toxicity. Patients should be educated for their increased risks of these events and taught to monitor and report the appropriate symptoms.

Approximately 4.8% of patients enrolled in GEOMETRY mon-1 experienced ILD or pneumonitis, and 1.9% of these cases were graded as grade 3. One patient died as a result of ILD/pneumonitis and 9 patients discontinued treatment because of ILD/pneumonitis complications.

Any signs of pulmonary symptoms, including dyspnea, cough, and fever should be monitored and reported immediately. The median time-to-onset time for grade 3 or worse events was 1.8 months (0.2 months – 1.7 years). Capmatinib should immediately be withheld if this AE is suspected and discontinued if it is positively identified.

An increased in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 15% of patients who received capmatinib, of which 7% became grade 3 or 4. Three patients discontinued treatment because of hepatotoxicity.

Liver function should be tested at baseline and monitor every 2 weeks throughout the first months of treatment. These tests should include ALT, AST, and total bilirubin. After 3 months, la should be collected once a month, or as clinically indicated, with more frequent routine assessment for those who develop increased transaminases or bilirubin. If severe AEs begin to develop, it may be appropriate to withhold, dose reduce, or permanently discontinue capmatinib.

Fourteen patients experienced elevations in amylase and lipase levels, 7% and 1.9% of whom experienced grade 3 and 4 severity, respectively. Three patients discontinued because of pancreatic toxicity. One patient permanently discontinued treatment because of grade 3 pancreatitis.

Amylase and lipase levels should be assessed at baseline and regularly monitored throughout treatment. If severe AEs begin to develop, it may be appropriate to withhold, dose reduce, or permanently discontinue the agent.

Overall, the most common serious AEs included dyspnea (7%), pneumonia (7%), pleural effusion (4.3%), musculoskeletal pain (3.8%), general physical health deterioration (2.9%), ILD/pneumonitis (2.7%), and vomiting (2.4%). Fatal AEs occurred in 0.5% of treated patients, with pneumonitis representing the leading specified cause (0.3%).

Seventeen patients needed to discontinue because of an AE. The AEs most commonly associated with discontinuation included ILD/pneumonitis (2.4%), edema (2.4%), fatigue (1.3%), and pneumonia (1.1%).

Dose interruptions occurred in approximately 57% of patients on the trial. The AEs most likely to require a dose interruption included edema, increased blood creatinine, nausea, increased lipase, vomiting, increased ALT, dyspnea, pneumonia, fatigue, increased amylase, increased AST, musculoskeletal pain, abdominal pain, and increased blood bilirubin. The AEs most likely to require a dose reduction were edema, increased ALT, and increased blood creatinine.

According to a news release, nearly 70% of patients with NSCLC have a genomic mutation, and 3% to 4% of patients with NSCLC have 

The approval of this agent represents another targeted therapy for those 4000 to 5000 patients with this oncogenic driver mutation.

FDA approves capmatinib for metastatic non-small cell lung cancer. FDA. August 10, 2022. Accessed August 11, 2022. 

Capmatinib. Prescribing information. Novartis Pharmaceuticals Corp; 2022. Accessed August 11, 2022. https://bit.ly/3JLN2kQ

Novartis announces FDA approval of MET inhibitor Tabrecta for metastatic non-small cell lung cancer with METex14. May 6, 2020. Accessed August 11, 2022. https://bit.ly/2SIEmTc

Articles

The FDA has granted capmatinib regular approval for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to MET exon 14 skipping. The drug comes with warning for pneumonitis, hepatotoxicity, and pancreatic toxicity. 

Capmatinib Snags Full FDA Approval for MET Exon 14 Skipping NSCLC

The great resignation, spurred by the COVID-19 pandemic, has taken an enormous toll on the nursing field. 

In a poll conducted in September 2021, results showed that 20% of health care professionals had abandoned their position since February 2020.

Furthermore, a report examining labor trends in 2020 found that 24% of all hired nurses leave their position within 1 year of being hired.

 Coupled with increasing demand and a depletion of resources, many units are losing nurses  and other staff at an unsustainable rate.

From a financial perspective, the average cost of a single bedside registered nurse (RN) turnover is $40,038, and cost of turnover per health care system for every 1000 nurses hired is $9,609,120.

Although there is no single solution to address the staffing crisis, institutions can start with the onboarding process to better engage and retain employees. Solidified onboarding processes, structured mentorship programs, and clear pathways for career development are crucial factors in ensuring that new hires feel valued and supported.

“Once you invest in a person—through the process of hiring, interviewing, bringing them through a solid orientation—you show them that you want them to stay,” Nicola Stewart, MHL, RN-NC, BSN, OCN, a complex gastrointestinal cancer nurse navigator at Methodist Healthcare at Sarah Cannon Cancer Institute in San Antonio, Texas, explained in an interview with 

. “[It is important] to focus on that individual and to create a family atmosphere. It is how you inspire loyalty and how you create a support system at work.”

Stewart joined Lance Ortega, MBA, BSN, RN, OCN, director of nursing services at Texas Oncology in Dallas; and Lyndsey Conway, MN, RN, BMTC, of Seattle Cancer Care Alliance in Washington, in a presentation at the 2022 Oncology Nursing Society Congress.

Their presentation, “Mission Possible: Enhancing Oncology Nurse Recruitment and Retention,” highlighted the causes of RN turnover, including stress, burnout, inflexibility, lack of representation, too much overtime, and external competition. They also presented opportunities for institutions to address those root causes. One of those considerations is through enhanced onboarding strategies and ongoing developmental support.

“There is no 1 magical fix to correct these issues,” Ortega said in an interview with Oncology Nursing News®. “The series of events that led us here, as an industry and profession, [was] complex, longstanding, and sometimes subtle but profound. That means our solutions to these dilemmas will need to be creative, innovative, and more outside-the-box than ever before. The solutions will also not occur overnight or even on the first attempt, and our path forward will be long and very difficult at times. However, for the sake of our patients and the overall health care system, we need leaders and organizations [to be] committed to and engaged in changing the face of nursing for the future in such a way that we reinvigorate our staff to remember their reasons why they became, and continue to be, a nurse.

One critical aspect of a good onboarding program is mentorship, Stewart explained in the presentation.

 Everyone needs guidance, new nurses especially, and the key to ensuring this is through a well-defined mentorship program, she said. Preceptors from different units should be intentionally matched to preceptees and rotated among different preceptees during orientation to expose a new hire to multiple people because, as Stewart explained, 1 person never has all the answers.

Incentivizing mentors and preceptors with bonuses helps ensure that teachers are enthusiastic about educating the new nurses. “Identifying mentorship opportunities and having a good, quality preceptor [is critical],” Stewart said. In addition, training preceptors on how to mentor and instruct new staff by providing clear guidelines and expectations for the onboarding process should be a key pillar of the program. Regular check-ins to evaluate the progress of the trainee, as well as the enthusiasm and desire of the mentor to continue precepting, are also important. 

“Even the best preceptors need breaks from time to time,” Ortega said, adding that “new nurses need methodical and unrushed onboarding with a preceptor who is willing and wanting to onboard these nurses in an environment that is as conducive to learning as possible.”

A methodical and unrushed program, according to Ortega, comprises evidence-based materials and competency cutoffs that have been vetted by those currently performing the role. The program should have a timeline for milestones that is both realistic for the position and tailored to the new nurse’s learning style and experience level. Furthermore, Ortega said, environment should be a key consideration when thinking about onboarding. A busy or chaotic floor or unit may not be conducive to learning and development. Identifying floors or areas that are ideal for training and onboarding can contribute to an improved overall learning environment.

Stewart also recommended building the team through enthusiasm and positivity. She acknowledged that it is a difficult time to work in nursing, and that listening to colleagues and supporting them is important to show them that you are there for them.

“Once you create that family and that bond, relationships have been created. It’s difficult to [want] to walk away from that,” Stewart said. Finally, investing in an individual and their future with their company is a great way to establish a desire to continue with the company. “Appreciate the loyalty, offer longevity bonuses, and be there for one another,” Stewart said.

Anna Vioral Gavin PhD, MEd, RN, OCN, BMTCN

“When I moved to ambulatory oncology, there was [no] infrastructure built for onboarding oncology nurses,” Anna Vioral Gavin, PhD, MEd, RN, OCN, BMTCN, reflected in an interview with Oncology Nursing News®. “It’s taken us 3 years to get to where we are today—to build the infrastructure to properly onboard an oncology nurse—with 26 geographically dispersed locations.”

Vioral, who is director of oncology practice and professional development at the Allegheny Health Network Cancer Institute in Pittsburgh, Pennsylvania, helped to launch a successful oncology practice and professional development program at her institution with a focus on building resiliency in the ambulatory setting.

One challenge was how to centralize an innately decentralized onboarding experience. This led to the development of the Oncology Professional Proficiency Initiative, an individualized onboarding experience within the Allegheny Health Network.

“In-patient [nursing] has a lot in infrastructure for onboarding, but ambulatory settings tend to be all over the place,” Vioral said. 

Vioral’s professional development team meets with new oncology nurses during the week following their initial hire, along with the preceptor and the manager. The novice nurses are asked to complete a self-assessment of skills and past experience, which provides direction for what they should be focusing on in their biweekly meetings.

“If they’ve been starting [intravenous infusions] IVs for 20 years, we spend [approximately] 10 minutes with them teaching them our way,” Vioral explained. “Whereas, if they’ve not done certain types of infusions, then we spend that time working on those infusions.”

The biweekly meetings are scheduled over 90 days, and during that time the new hires are expected to meet the rudimentary goals of oncology nursing. Another unique piece of the proficiency initiative is that in the first 2 weeks of onboarding, the nurses’ main responsibility is to learn more about the roles in the institute and the locations.

“[New nurses] are assigned a role observation for their location. For example, if they were hired into medical oncology, they have a document that has them sit with each role in each department, including medical oncology, radiation oncology, support care services, hematology, and gynecologic oncology,(surgical oncology, is optional). They will sit with the front desk for anywhere from 30 minutes to 2 hours; they will go with the medical assistant; they will go with the clinical pharmacists and watch how [prescriptions] are prepared, verified, and mixed. They [will gain an understanding of] the timeframe of why things take solong back there with certain drugs. That helps them in the front end, when they’re administering [drugs, because] they understand the workflow process of the office. [Nurses will] follow a physician and an advanced practice nurse. They even spend a full day in radiation oncology observing the workflows there. And then we set up informal connections with all our supportive care services,” Vioral said.

Trainees receive a document that helps them identify who are the institute’s genetic counselors, who are members of nutritional services, etc. This becomes an additional resource for them, allowing them to know who plays what role in the institute. The team also hosts an “Oncology Interprofessional Onboarding Course,” which is held every month for all new hires across the cancer institute. The first 4 hours encompass soft skills; such as conflict resolution, de-escalation, and communication skills however, the afternoon features breakout discipline-based sessions. For nurses, there is a special emphasis on supportive care therapies and nononcology infusions, as well as oncologic emergencies and management of patients with cancer .

Notably, all new hires are all expected to test out of the chemotherapy program, even if they arrive with a chemotherapy card.

“This serves as a bridge into how we do things here,” Vioral explained. “Even if they’ve been an oncology nurse for 30 years, it gets them used to our organization and how we do things.”

The program has been fruitful. Many recently hired nurses shared in an anonymous survey that the program not only helped them feel supported and confident to independently care for their patients, but they also felt it built their resilience.

One nurse said that the Allegheny Health Network onboarding experience helped them “bounce back from difficult situations because the training taught how to step back and remain calm to handle patients professionally and efficiently.” Other new hires’ responses stated that the program was “incredibly helpful” in becoming familiar with “all the roles involved with the Allegheny Health Network team” and let them focus on the areas they individually neededassistance with.

One nurse shared that the program helped build resilience by assuring new hires that the role takes to time to adapt to; another shared that they really appreciated the fact that someone was consistently checking up with them to ensurethey understood their role.

“This onboarding program was the best I’ve ever had,” one respondent shared.

When it comes to training, faster isn’t always better, according to Vioral. Hasty training can lead to attrition if employees do not feel they have the resources to successfully do their job.

“I love patients, but staff is what makes the difference,” Vioral, who has worked in patient care for more than 33 years, said. “If an employee is not [properly] trained, [does] not like what they are doing, or we are not meeting their needs, they are going to leave—which [affects] the quality of care we give to our patients.”

When employees leave, Vioral’s team needs to bring more nurses in and train them, which can be costly. This can be another barrier to care. However, whenever the opportunity presents itself, Vioral will try to shift a nurse to a new area rather than see them leave. “So rather than lose them from the organization, I will do everything in my power to get them to stay,” Vioral said.

When first initiating this program, something that Vioral frequently was asked was, “Why are you stealing my nurse?”

“That was a huge barrier,” she said. “I would say, ‘I’m not stealing your nurse.

It’s an oncology nurse with a very sound understanding of oncology. They’re going to leave if they lose interest.’” Vioral noted, “We have medical oncology, surgery, chemo, nurse navigation….We have so many opportunities. Some nurses do not want to move up; they want to stay lateral and move into different roles and learn them. We’re professionally developing them into a new area of nursing.”

When you move nurses and do not have to retrain new nurses, you save yourself money and time and become more efficient, Vioral said. 

The decision to allocate sources to the outpatient setting can sometimes be a hurdle, she added. Inpatient services may feel as though the time and money spent on training is a loss to their department. However, according to Vioral, “The outpatient setting is where oncology is now. It is not all inpatient nursing anymore. If you have an oncology nurse who wants to do that, they are going to go to another organization or ambulatory to get what they need.” Ultimately, lateral moves are a way to retain nurses across the institution, she said.

Similarly, Stewart emphasized the need to look at an individual’s potential growth beyond their current position during the onboarding process. “A new patient care assistant on their first day could be the future chief nursing officer,” Stewart said. “You never know what [individuals] will want to do in the future and what capabilities they possess. You want to grow these [employees] and avoid turnover so you can build within for generations to come.”

“Investing in our nurses is key to future retention,” Ortega said. “If you survey most nurses, specifically surrounding their reasons for staying with their current company, the vast majority of them will say their coworkers and patients keep them there. Strategies for retaining nurses needs to focus on those areas as a foundation and expand from there. So I think about things [such as] increased educator positions and roles to engage and knowledge- share experiences with the staff and even patients. Survey the nurses to see what is most appealing to them. This could include things [such as] different scheduling options, retention bonuses, different salary models, new workflows and staffing patterns.”

Overall, experts agreed that engagement is at the heart of retention. Listening to new nurses and acting on their behalf goes far in making them feel heard and valued. By investing at the beginning, most organizations will see increased loyalty and, ultimately, boosted retention. 

1. Ortega L, Stewart N, Conway L. Mission possible: enhancing oncology nurse recruitment and retention. Presented at: 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022, Anaheim, CA.

2. Galvin G. Nearly 1 in 5 health care workers have quit their jobs during the pandemic. Morning Consult. October 4, 2021. Accessed July 14, 2022. https://morningconsult.com/2021/10/04/

health-care-workers-series-part-2-workforce/

3. NSI National Health Care Retention & RN Staffing Report. NSI Nursing Solutions, Inc. Accessed July 11, 2022. https://www.nsinursingsolutions.com/Documents/Library/NSI_ National_Health_Care_Retention_Report.pdf

In an unprecedented age of health care burnout, hospital administrators may
need to think outside of the box to find ways to engage and support employees.

Structured Onboarding Processes Boost Employee Retention 

The addition of novel targeted and immunotherapies, as well as antibody-drug conjugates, into the urothelial cancer (UC) treatment paradigm has accentuated the importance of the oncology nurse’s role in patient education and symptom management, according to Laura Wood, RN, MSN, OCN.

“I’d like nurses to know that we’ve made significant strides in improving treatment options for patients with urothelial carcinoma,” Wood said in an interview with 

 “Nurses play a critical role in providing education to patients and caregivers, ensuring that [adverse effects] AEs and [immune-related AEs] irAEs are identified early so appropriate interventions can be initiated, [all] while continuing to provide emotional support [to patients] as they navigate the cancer journey.”

Wood, a retired oncology nurse specialist with the Cleveland Clinic Taussig Cancer Institute, recently presented on treatment updates in the schema as part of the 

®, she highlighted avelumab (Bavenzio), erdafitinib (Balversa), and enfortumab vedotin-ejfv (Padcev) as 3 key drugs that nurses caring for patients with urothelial carcinoma should be aware of underscoring what makes them unique and what the best AE management looks like with them.

The current standard of care maintenance treatment for patients with locally advanced or metastatic urothelial cancer that has not progressed with frontline platinum-based chemotherapy is avelumab. This drug was approved for patients who have received prior treatment with at least 1 line of platinum-based chemotherapy following positive results from the JAVELIN Bladder 100 trial (NCT02603432),

 which compared the efficacy of avelumab plus best supportive care (BSC) against BSC alone.

An analysis of long-term outcomes found that the 30-month overall survival (OS) rate with avelumab (n = 350) was 43.7% compared with 33.5% with BSC (n = 350). In addition, the median progression-free survival (PFS) was 5.5 months vs 2.1 months (HR, 0.54; 

 < .001) in the experimental and control arms, respectively, and the 30-month PFS rate was 19.3% vs 6.3%, respectively.

“Nurses need to be aware that this treatment is available, [and] that it is an approved option for patients who are doing well and benefiting from first-line platinum-based chemotherapy,” Wood said. “They also need to know that it requires pre-medication for the first 4 infusions due to the potential for an infusion-related reaction. That is unique compared to the other checkpoint inhibitors we use in oncology.”

As of August 2022, National Comprehensive Cancer Network guidelines dictate that patients with locally advanced or metastatic disease who are cisplatin-eligible may receive cisplatin-based combination chemotherapy followed by avelumab maintenance therapy or dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (DDMVAC) with growth-factor support for 3 to 6 cycles followed by avelumab maintenance therapy.

Patients who are cisplatin ineligible may receive gemcitabine plus carboplatin chemotherapy followed by avelumab maintenance therapy. They may also receive atezolizumab (Tecentriq) or pembrolizumab (Keytruda) if their tumors express PD-L1 and they are not eligible for any platinum-based chemotherapy regardless of PD-L1 expression. They may also receive gemcitabine with or without paclitaxel.

For second-line treatment, the preferred agent is pembrolizumab (category 1 post-platinum). Other favorable alternatives to pembrolizumab include the immune checkpoint inhibitors, nivolumab (Opdivo) and avelumab; and monotherapy with the agents erdafitinib, and enfortumab vedotin. Paclitaxel, docetaxel, and gemcitabine are also viable options included in the guideline.

In certain circumstances, depending on a patient’s prior treatment history, the following options may also be useful: ifosfamide, doxorubicin, and gemcitabine; gemcitabine plus paclitaxel; gemcitabine plus cisplatin; and DDMAC with growth-support factor.

Erdafitinib is approved for patients with locally advanced or metastatic UC that is susceptible to 

 genetic alterations and that has progressed during or following at least 1 line of platinum-based chemotherapy—including within 12 months of neoadjuvant or adjuvant therapy.

The companion tests to determine if a patient is eligible for erdafitinib are the Theraseen GRGR RGQ RT-PCR kit, and the formalin-fixed, paraffin embedded (FFPE) tissue sample.

“Tumor testing is required,” Wood stressed. “There’s biomarker testing involved, and [erdafitinib] is approved for patients who have progressed during or following frontline platinum-based chemotherapy. [It] remains a mainstay in our treatment plan within 12 months of neoadjuvant or adjuvant therapy.”

Notably, Wood highlighted, “The unique component to erdafitinib is that there is the potential for dose titration.”

The starting dose for erdafitinib is 8 mg once daily (two 4-mg tablets). After the patient has been taking erdafitinib for 14 to 21 days, the dose can be increased to 9 mg (three 3 mg tablets) so long as they are able to tolerate the drug and their serum phosphate labels are at appropriate levels.

Nurses should note that the treatment can increase a patient’s phosphorus levels, putting them at risk of hyperphosphatemia.

“Again, we’re looking at sequential therapy,” Wood said. “One of the unique [AEs] is the potential for an increased phosphorus level and that is something we do not normally include in our laboratory panels. But it is critical to monitor for that with [and to] educate patients about a low phosphorus diet as well.”

Patients should restrict phosphate intake to 600 mg to 800 mg daily. However, if serum phosphate exceeds 7.0 mg/dL, it may be appropriate to add an oral phosphate bunder until the levels return to less than 5.5 mg/dL.

Erdafitinib is also be associated with ocular toxicities. According to the package insert, 19% of patients experienced all-grade dry eye with the agent, 17% experience blurred vision, 6% cataracts, and 5% keratitis. The percentage of patients who experience grade 3 or greater ocular toxicities was much smaller at 1%, 0%, 2% and 3%, for dry eye, blurred vision, cataracts, and keratitis, respectively.

Moreover, 25% of patients experience serous retinopathy/retinal pigmen epithelial detachment (CSR/RPED). The median onset time to first occurrence was 50 days.

“Nurses need to be aware of the potential for increased phosphorus levels and the need to educate patients and caregivers about the drug dose and drug formulation change if dose escalation is appropriate,” Wood summarized.

The last drug that Woods covered in her presentation was enfortumab vedotin.

“Enfortumab vedotin is an antibody-drug conjugate Targets Nectin-4 protein on UC cells,” she said to 

 “The drug binds with the Nectin-4 protein, the linker dissolves, and the microtubular payload is released—leading to cell cycle arrest and apoptosis.”

The agent is indicated for adults with locally advanced or metastatic disease who have previous PD-1 or PD-L1 inhibition and platinum-based chemotherapy. Patients receiving this drug must be ineligible for cisplatin-containing chemotherapy and must have previously received at least 1 or more prior lines of therapy.

The recommended dose for enfortumab vedotin is 1.25 mg/kg. The maximum dose is 125 mg/kg. It is administered intravenously (IV) over 30 minutes on days 1, 8, and 15, as part of a 28-day cycle.

Nurses should be aware that this agent can cause severe and fatal cutaneous AEs, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These reactions frequently occur throughout the first treatment cycle but may also occur later.

The drug also comes with warning for skin reactions, hyperglycemia and diabetic ketoacidosis, pneumonitis, peripheral neuropathy, ocular disorders, dry eye symptoms, blurred vision, increased lacrimation, conjunctivitis, and infusion site extravasation.

Patients should be educated on the risk of infusion site reactions, hyperglycemia, pneumonitis, and vision changes. They should also be advised to use artificial tear substitutes to both prevent or treat dry eyes. Moreover, baseline assessments and continued monitoring for peripheral neuropathy are advised.

According to Wood, there are numerous investigative therapies with promising efficacy and safety profiles. One of these agents is N-803, a mutant IL-15–based immunostimulatory fusion protein complex.

, findings from the ongoing phase 2/3 QUILT 3.032 trial (NCT03022825) showed that among 160 patients with carcinoma in situ, or papillary Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer, the complete response rate was 71% (95% CI, 60.1%-80.5%). The median duration of response was 26.6 months and at a 2-year data cut-off, the OS rate was 100%.

Based on findings from the QUILT 3.032 trial, a biologics license application has been filed with and 

. The decision date has been set for May 23, 2023, under the Prescription Drug User Fee Act.

Wood highlighted a biomarker gaining traction in UC—Trop-2. In May 2021, the 

FDA granted sacituzumab govitecan (Trodelvy) accelerated approval

 based on phase 2 findings from the TROPHY-U-01 trial (NCT03547973).

Data showed a viable response among patients with pretreated metastatic UC who received the Trop-2-directed antibody-drug conjugate. In a single cohort of 133 patients with a median range of 3 prior lines of therapy, the objective response rate was 27% and a measurable disease decrease was observed in 77% of patients. In addition, the median PFS was 5.4 months, and the median OS was 10.9 months.

Continued approval is contingent on findings from the confirmatory phase 3 TROPiCS-04 trial (NCT04527991).

Woods noted in her presentation that nurses should encourage and support participation in clinical trials and give continued attention to understanding the importance of pre-treatment and on-treatment biopsy requirements for biomarker testing, as well as leveraging multidisciplinary care including palliative care for disease-related symptom management.

Wood L. Novel approaches to Renal and Urothelial Cancers. Presented at: 

 School of Nursing Oncology™; July 29-30, 2022; San Diego, CA.

Powles T, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): long-term follow-up results from the JAVELIN Bladder 100 trial

. 2022;40(suppl 6):487. doi:10.1200/JCO.2022.40.6_suppl.487

NCCN. Clinical practice guidelines in oncology. Bladder cancer, version 2.2022. Accessed August 9, 2022. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf

Balversa. Prescribing information. Janssen Products, LP; 2019. Accessed August 10, 2022. 

Padvec. Prescribing information. Astellas Pharma US, Inc; 2019. Accessed August 10, 2022. 

Chang SS, Chamie K, Gonzalgo ML, et al. Positive efficacy and safety phase 3 results in both CIS and papillary cohorts BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) after IL-15RαFc superagonist N-803 (Anktiva) and BCG infusion. 

. 2022;40(suppl 6):431. doi:10.1200/JCO.2022.40.6_suppl.431

ImmunityBio announces FDA acceptance of biologics license application for N-803 in BCG-unresponsive non-muscle-invasive bladder cancer carcinoma in situ. News release. Immunity Bio. July 28, 2022. Accessed August 10, 2022. 

Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. 

. 2021;39(22):2474-2485. doi:10.1200/JCO.20.03489

FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed August 10, 2022. https://bit.ly/3tgxmgy

Avelumab, erdafitinib, and enfortumab vedotin-ejfv are 3 critical drugs in the treatment of urothelial cancer with distinct safety profiles, according to a presentation at the 6th Annual School of Nursing Oncology™ Meeting. 

Approaches to Urothelial Care Call for Nuanced AE Management

A biologics license application (BLA) for the IL-15 superagonist N-803 has been accepted and will undergo review for the treatment of patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS), regardless of T1 or Ta disease.

A decision date has been set for May 23, 2023, under the Prescription Drug User Fee Act.

The BLA is based in part on findings from the ongoing phase 2/3 QUILT 3.032 trial (NCT03022825), in which 71% (95% CI, 60.1%-80.5%) of patients with BCG-unresponsive NMIBC who progressed on prior treatment achieved a complete response (CR). The 12-month CR rate with the regimen was 62% (95% CI, 48%-74%); at 24 months, this rate was 52% (95% CI, 37%-65%).

If approved, N-803 plus BCG would represent the first immunotherapy combination for this indication in 23 years that can be delivered directly to the bladder to generate natural killer (NK) cells and T cells.

“This BLA acceptance brings us a very important step closer to being able to offer this promising combination therapeutic to more people living with NMIBC and, ultimately, reduce the incidence of cystectomies,” Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer at ImmunityBio, stated in a press release. “This is a compelling example of the power of inducing trained innate immune memory to potentially provide long-term, durable effects against serious, life-threatening diseases.”

N-803 is an antibody cytokine fusion protein that generates NK and T cells that, when combined with BCG, results in a synergistic immune response.

Previously, N-803 was granted a breakthrough therapy designation and fast track designation for use in combination with BCG in patients with BCG-unresponsive NMIBC CIS.

QUILT 3.032 is an open-label, multicohort, multicenter study that enrolled patients with histologically confirmed BCG-unresponsive disease with persistent or recurrent CIS, with or without recurrent Ta or T1 disease. Patients were enrolled within 1 year of receiving BCG. Those with CIS comprised cohort A, and those with papillary histology (n = 77) made up cohort B.

Patients received 50 mg of intravesical BCG in combination with 400 µg of N-803 weekly for 6 cycles followed by 6 cycles of maintenance treatment in those who experienced a CR for up to 2 years. Those who did not experience a CR but responded to treatment were allowed to receive another 6 cycles of re-induction with the combination regimen.

The primary end point was CR at any time, and secondary end points included CR duration, cystectomy avoidance, and time to cystectomy. Serious toxicities and immune adverse effects (AEs) were also evaluated.

Additional findings presented during the 2022 Genitourinary Cancers Symposium demonstrated that with a median duration of follow-up of 23.9 months (range, 0.3-37.5), the median duration of response (DOR) was 24.1 months (95% CI, 9.9-not reached) in cohort A.2 Sixty-two percent (95% CI, 48.0%-73.5%) of patients experienced a DOR of at least 12 months, 55% (95% CI, 40.1%-67.3%) experienced a DOR of at least 18 months, and 52% (95% CI, 37.0%-64.9%) had a DOR of at least 24 months.

Moreover, the cystectomy avoidance rate was 93%, and the median time to cystectomy was 5.1 months.

The 24-month rate of bladder cancer–specific progression-free survival was 91% (95% CI, 81.2%-95.4%), and the 24-month bladder cancer–specific overall survival rate was 100%.

In terms of safety, no patients in cohort A experienced treatment-related grade 4 and 5 AEs, treatment-related serious AEs, or immune-related AEs. The most common grade 1/2 AEs included dysuria (22%), pollakiuria (19%), and hematuria (18%). All grade 3 AEs occurred in less than 1% of patients, which included arthralgia, bacteremia, dysuria, encephalopathy, Escherichia bacteremia, hematuria, myalgia, pain in extremity, pollakiuria, sepsis, urinary tract infection, and urine flow decrease.

“We are pleased the FDA has begun its review, and ImmunityBio is prepared to move rapidly to manufacturing and marketing should the Agency approve our therapeutic for this indication,” Richard Adcock, president and chief executive officer of ImmunityBio, said.

ImmunityBio announces FDA acceptance of biologics license application for N-803 in BCG-unresponsive non-muscle-invasive bladder cancer carcinoma in situ. News release. Immunity Bio. July 28, 2022. Accessed August 1, 2022. 

A biologics license application for the IL-15 superagonist N-803 has been accepted and the agent will be reviewed for the treatment of patients with Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer carcinoma in situ.

N-803 BLA Undergoes Review For BCG-Unresponsive Non–Muscle Invasive Bladder Cancer in Situ

VEGF tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) regimens have played a significant role in improving progression-free survival (PFS) and overall survival (OS) in patients with renal cell carcinoma (RCC), according to Laura Wood, RN, MSN, OCN.

“We’re seeing impressive improvements in long-term outcomes with the newer regimens in advanced renal cancer,” Wood, who is a retired oncology nurse specialist at Cleveland Clinic, said in an interview with 

 “TKI/IO combinations have made a huge impact on clinical outcomes and quality of life for patients with advanced RCC.”



Wood recently gave a talk on updates in renal cell and urothelial carcinomas as part of the 

 meeting. Following the meeting, Wood met with 

 to give a recap of the key takeaways in RCC for nurses.

In her presentation, Wood noted that the treatment of metastatic RCC has undergone multiple eras, starting with the use of cytokine-directed therapies, such as IL-2 and IFNα.

The targeted therapy era ushered in numerous treatments, including sorafenib (Nexavar), sunitinib (Sutent), temsirolimus (Torisel), bevacizumab (Avastin), everolimus (Afinitor), pazopanib (Votrient), axitinib (Inlyta), cabozantinib (Cabometyx), lenvatinib (Lenvima), and tivozanib (Fotdiva).

In 2015, the first immunotherapy entered the scene with the approval of nivolumab (Opdivo) and soon thereafter the combination of ipilimumab (Yervoy)/nivolumab was added to the landscape as well. In 2019, the first combination of immunotherapy plus VEGF/TKI was approved, marking a new and exciting area in the treatment of renal cell carcinoma.

Two such combinations were approved in 2019: pembrolizumab (Keytruda) and axitinib, and avelumab (Bavencio) and axitinib. In 2021, 2 more combinations were added to the fold: nivolumab/cabozantinib and pembrolizumab/lenvatinib.

According to Wood, there are 4 key studies which have drastically shifted VEGF/TKI combination regimens to the forefront of the treatment landscape. These include CheckMate 214 (NCT02231749), JAVELIN Renal 101 (NCT02684006), KEYNOTE-426 (NCT02853331), and CheckMate 9ER (NCT03141177).

The CheckMate 214 trial was a phase 3 trial which randomly assigned a total of 1096 patients to receive either nivolumab plus ipilimumab intravenously (IV) every 3 weeks for 4 doses followed by nivolumab for 2 weeks, or 50 mg of daily oral sunitinib (Sutent) for the first 4 weeks of a 6-week cycle. Nivolumab doses were 3 mg/kg and ipilimumab was 1 mg/kg.

The median follow-up time was 25.2 months, at which time it was revealed that among intermediate- and poor-risk patients (n = 550), the 18-month OS rate was 75% (95% CI, 70%-78%) with dual immunotherapy and 60% (95%, 55%-66%) with sunitinib. Moreover, the median OS was not reached with nivolumab plus ipilimumab compared with 26.0 months with sunitinib (HR, 0.63; 

Between the 2 groups, the objective response rate was 42% vs 27% (

 < .001) and the complete response rate was 9% vs 1%; median PFS was 11.6 months and 8.4 months, respectively (HR, 0.82; 

Findings from the positive trial supported the FDA’s 

JAVELIN was a single-group, phase 1b trial which randomly assigned 886 patients 1:1 to receive either IV avelumab every 2 weeks plus 5 mg daily oral axitinib or 50 mg of daily oral sunitinib for the first 4 weeks of a 6-week cycle. The dose for avelumab was 10 mg/kg.

In the combination arm (n = 442), the median PFS was 13.8 months vs 8.4 months in the single-agent arm (n = 444; HR, 0.69; 95% CI, 0.56-0.84; 

< .001). In an analysis of patients with PD-L1 expressing tumors, the median PFS was 13.8 months vs 7.2 months, respectively (HR 0.61; 95% CI, 0.47-0.79; 

 < .001). In the same subpopulation, the overall response rate was 55.2% vs 25.5% with the combination and single-agents, respectively, and the median OS was 11.6 months vs 10.7 months.

The phase 1b KEYNOTE-426 trial randomly assigned patients 861 to receive either combination therapy with IV pembrolizumab and oral axitinib (n = 432) or sunitinib (n = 429). Pembrolizumab was administered at a dose of 200 mg every 3 weeks and axitinib was taken twice daily at a dose of 5 mg. Sunitinib was taken at a dosage of 50 mg once daily for the first 4 weeks of a 6-week cycle.

The median follow-up time was 12.8 months. At follow-up, the percentage of patients who had survived the first 12 months was 89.9% with pembrolizumab/axitinib vs 78.3% with sunitinib (HR 0.53, 95% CI, 0.38-0.74; 

< .0001). The objective response rate between the 2 groups was 59.3% (95% CI, 54.5%-63.9%) and 35.7% (95% CI, 31.1%-40.4%).

CheckMate 9ER was a phase 3, open-label trial which randomly assigned 651 adults to receive either nivolumab (240 mg every 2 weeks) and cabozantinib (40 mg once daily) or 50 mg of daily oral sunitinib 4 weeks of each 6-week cycle.

At a median follow-up of 18.1 months, the median PFS was 16.6 months (95% CI, 12.5-24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0-9.7; HR, 0.51; 95% CI, 0.41-0.64; 

< .001). The probability of surviving 12 months with the dual immunotherapy was 85.7% (95% CI, 81.3%-89.1%) and 75.6% (95% CI, 70.5%-80.0%; HR, 0.60; 98.89% CI, 0.40-0.89; 

 = .001) with the targeted therapy. The overall response rate between the 2 cohorts was 55.7% and 27.1%, respectively (

Findings from the trial supported the FDA’s 

Nursing Considerations With Combination Treatment

The goal behind combination treatment is to combine the mechanism of actions of the drugs with single-agent efficacy—ideally using drugs with limited overlapping toxicities which can be given to a patient at their respective full dose.

When caring for patients with RCC, baseline symptom assessment is key, Wood noted. This includes reviewing the comorbidities, concomitant medications, and any adverse events (AEs) experienced with prior lines of therapy.

Patient and caregiver education should revolve around key indicators that should result in a phone call to the oncology care team.

Further, details regarding AEs, specific interventions, and assessing for improvement is key for nurses to consider, she added, particularly with the blossoming number of VEGF/immunotherapy combinations.

For example, AEs commonly associated with VEGF-targeted therapy include hypertension, taste changes, mucositis, dyspepsia, myelosuppression, and hand-foot syndrome.6 In contrast, common AEs of immunotherapy include pruritis, myocarditis, adrenal insufficiency, rash, pneumonitis, colitis, and hepatitis.

However, it is important to note that certain AEs may overlap between the 2 treatment approaches. These include rash, fatigue, diarrhea, LFT elevations, hypothyroidism, anorexia, and altered mental status. If a patient is experiencing one of these symptoms, it is important to determine which drug is causing it to properly address it.

Taking the drugs half-life into consideration is a good place to start, Wood said in her presentation, citing that the therapeutic half-life for axitinib, cabozantinib, lenvatinib, pazopanib, and sunitinib, are approximately 2.5 to 6 hours, 120 hours, 28 hours, 31 hours, and 40 to 60 hours, respectively. Moreover, some experts have suggested that in a patient being treated with axitinib plus pembrolizumab, for example, stopping the targeted treatment for a few days may be a way to rule out whether it is a targeted or immune-related toxicity, since an axitinib-induced toxicity would be expected to significantly improve with cessation of targeted therapy and an immune-related AE would not improve at all.

“Nursing best practices include detailed education for patients and caregivers regarding early identification and intervention for possible immune-related AEs so oncology providers can minimize possible negative [effects] on treatment outcomes and provide the best opportunity for patients to have successful treatments,” Wood told 

The Future of RCC and Investigative Treatments At Play

As of August 2022, studies attempting to incorporate VEGF TKIs into the adjuvant setting have been unsuccessful

 and single-agent therapy is still the standard of care for treatment in the adjuvant setting, with sunitinib and pembrolizumab representing the 2 approved agents.

The EVEREST trial (NCT01120249) is an ongoing phase 3 trial assessing the safety and efficacy of everolimus in the adjuvant setting for patients with high-risk disease. At the 2022 ASCO Annual Meeting, the adjuvant use of the mTOR inhibitor was associated with a 21% reduction in the risk of recurrence or death compared with placebo for patients with very high-risk RCC, however, additional analyses of the study remain ongoing.

Moreover, biomarkers have yet to play a role in treatment-decision making in the RCC space but Wood encourages nurses to be aware of biomarkers as certain patients may be eligible for clinical trials.

“[Although] biomarkers play a role in some treatments for urothelial cancer, there are no current biomarkers that impact treatment decisions in RCC,” Wood said. “[However,] clinical trials in both malignancies include tumor biopsies for biomarker testing, and it’s important that nurses understand this and encourage patients to be willing to have tumor biopsies done as requested so we can improve our ability to individualize treatment recommendations based on the person’s tumor biology,” she concluded.

Motzer RJ, Tannir NM, McDermott DF, et al; CheckMate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. 

. 2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126

Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. 

In a presentation at the 6th Annual School of Nursing Oncology™, Laura Wood, RN, MSN, OCN, highlights key nurse takeaways with VEGF TKI/immune checkpoint inhibitor therapy for patients with renal cell carcinoma. 

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