All women with ovarian cancer should receive genetic testing, according to Paula Anastasia, RN, MN, AOCN. However, certain actionable targets may be missed depending on the tests ordered in the clinic.

“When we talk about genetic testing, germline testing, now we want panel testing because in addition to the 

 pathogenic variants, there are other pathogenic variants in that family [such as] 

,” says Anastasia, who notes that for nurses working at institutions without genetic counselors onsite, there are valuable genetic counselor services online, which not only provide tests but help contextualize the results for providers and patients alike.

Anastasia recently gave a talk on PARP inhibitor optimization as part of the 

® to discuss what nurses need to know about this class of agents.

There are 2 approved PARP inhibitors for ovarian maintenance therapy, Anastasia says. However, it is important to determine if a patient has a homologous recombination deficiency (HRD) to see if they are eligible for a PARP inhibitor, she adds, noting that studies have shown that patients with a germline mutation or an HRD-positive tumor have a better clinical benefit with a PARP inhibitor.

Lastly, Anastasia underscores the importance of a patient’s prior adverse effect profile from chemotherapy.

“We want to know: how did patients do with their frontline therapy?” she explains. “Did they require growth factors? Was there dose reduction? Do patients have a history of hypertension, which may indicate whether or not they would tolerate something like niraparib?”

All of these are important considerations, she concludes.

Videos

Paula Anastasia, RN, MN, AOCN, underscores the value of genetic testing in personalizing treatment decisions in ovarian maintenance therapy. 

Paula Anastasia Emphasizes Importance of Genetic Testing in Selecting Maintenance Therapy for Ovarian Cancer

Treatments for patients with Hodgkin and non-Hodgkin lymphoma have entered a new era with the advent of targeted and personalized therapies such as bispecific T-cell engagers (BiTEs) and CAR T-cell therapies.

“The future direction for lymphoma treatment is targeting the lymphoma and the signaling pathway of the B cell,” Leslie Smith, DNP, RN, APRN-CNS, BMTCN, AOCNS, said. “Most lymphomas are B-cell [lymphomas] and that’s really drilling down into what is happening at the cellular level, how the lymphoma cell is communicating, so [we’re seeing] very targeted therapy.”

Smith, a clinical nurse specialist at the National Institutes of Health (NIH), discussed treatment selection in this patient population and how new therapies are changing the lymphoma landscape.

How has the landscape for the treatment of lymphoma changed?

 Traditionally, both Hodgkin and non-Hodgkin lymphoma have been treated with chemotherapy; Hodgkin gets chemotherapy and radiation therapy [and] non-Hodgkin is treated with chemotherapy and then monoclonal antibodies, which changed the paradigm [and improved] survival for patients with non-Hodgkin in the late 1990s.

Now, lymphoma treatments are focused on the genetic drivers of the disease and as a consequence the genetic drivers lead to the signaling pathway. [We must then ask] what are the signaling pathways of the lymphoma cell that are altering the way the immune system or the lymphomas or the lymphocyte is interacting with its environment and becoming a lymphoma cell.

If we can target those pathways, it becomes targeted therapy, as opposed to general chemotherapy or radiation therapy. These include some traditional drugs, [such as] the immunomodulatory drugs lenalidomide [Revlimid] and thalidomide [Thalomid], and the BTK inhibitors ibrutinib [Imbruvica], acalabrutinib [Calquence], [and zanubrutinib (Brukinsa)]. In addition, checkpoint inhibitors have made a huge difference in relapsed [or] refractory disease.

You can’t have a discussion about [lymphoma] without talking about CAR T cells, which even though they have shown great response rates it has not been [inducing] remission for a lot of patients.

So, there are multiple drugs—BTK inhibitors, IMids, PI3K inhibitors—that target various parts of the signaling pathway that drive the development of lymphoma and [drive the] prevention of apoptosis.

How are BiTES playing a role in lymphoma treatment? What data support their use in the clinical setting?

BiTEs, such as blinatumomab [Blincyto], are important to talk about. [They] have shown early success as far as conferring remission. Blinatumomab specifically had a lot of toxicities in the trials and many patients with lymphoma came out early because of the neurotoxicity and they had grade 3/4 cytokine release syndrome [CRS].

In addition, there was not a sustained response, so patients relapsed within a few months after receiving the drug. There are newer BiTEs now, REGN1979 also called odronextamab, and glofitamab. Those have shown better response rates with lower toxicity—patients did not have neurotoxicity…or CRS. The debate is how to dose or administer the drug. Should it be a weekly infusion on a flat dose, or should it be an escalating dose type of infusion? [Investigators are] still trying to figure that out, but [early efforts are] showing some promise with getting patients in remission.

Interestingly, these drugs are showing better response in indolent lymphomas, especially follicular lymphoma, rather than the more aggressive lymphoma. There is still more work to be done looking at these drugs, but they are showing some promise.

Could you discuss the evolving role of CAR T-cell therapy in treating patients with lymphoma? What benefits and limitations are we observing regarding this treatment approach? What are your thoughts on incorporating CAR T-cell therapy into earlier lines of treatment?

CAR T-[cell therapy] has been a great drug for relapsed [or] refractory non-Hodgkin lymphoma, as far as confirming progression-free survival. However, similar to what we’re seeing in leukemia, [the] cancer is smart, it outsmarts us all the time. It changes its antigen receptors on the surface of the malignant cell and then we have loss of antigen and so any CAR T cells that are remaining in the patient’s body that are there and go unnoticed don’t have anything to attack. Now the malignant cell has transformed itself to be able to survive.

For patients, the progression-free survival rate in lymphoma for the CD19-[targeted] CAR T cells, which is mostly what’s approved now for lymphoma, is 30% to 50% [PFS rate]. At NIH, we’re looking at CAR T cells that target 2 antigens, such as CD19 and CD20; we’re trying to target 2 antigens on the surface of the receptor itself.

There’s [the question of] should we pair CAR T cells with checkpoint inhibitors because the CAR T cells also get exhausted, like the T cells in our normal immune system and the checkpoint inhibitors may take care of that. The TRUCKs, which stands for T cells redirected towards universal cytokine killing, [are armored CAR T cells]. They confer genes to help stimulate a big cytokine response within the immune system to kill the malignancy. [Approximately] half of patients will get a sustainable recovery, but as far as being used upfront, I think that’s the same discussion that hematologists have with the leukemia population. Should we use them first, reserve them for relapsed [or] refractory, should they be a terminal treatment in that patient gets CAR T, does it need a transplant, or should it be a bridge to transplant?

CAR T has a lot of [adverse] effects. An older patient may have more difficulty because non-Hodgkin lymphoma is a disease of patients older than 60 [years], maybe in their 70s. It is also very expensive, remaining about a half a million dollars to get this treatment and I think most places still require a caregiver to be with the patient during the initial few months. That can be a challenge for some [individuals] who have children, are working, or maybe do not have family and friends who are available.

But I think CAR T is showing promise and there was a new [therapy] just approved for mantle cell lymphoma [brexucabtagene autoleucel (Tecartus)] that got early approval [which is promising because] mantle cell lymphoma is a very rare, aggressive type of lymphoma. I think there’s a lot of room for CAR T but they're still manipulating the CARs to make a more effective response.

In your opinion, has CAR T-cell therapy impacted the suitability of autologous stem cell transplantation for certain patients with lymphoma?

I think it has. Transplant is not without risk. First you must find a donor—does a patient have a family member who is a matched-related donor because a match-related doner is better if they have the human leukocyte antigen [HLA] matching.

In older patients, transplant can sometimes be fatal. There’s the sequelae of transplant years down the line where patients are still prone to infection and secondary malignancies as time goes on over the general population. Perhaps CAR T for an older patient would be a better choice than transplant, especially since we have allogeneic CAR T cells, where you can get CAR T can come from a donor, and you don’t have to worry so much about the HLA matching as much as you do with a stem cell transplant. For some patients CAR T may be a better option then a transplant.

What are some important considerations when selecting a treatment regimen for a patient with lymphoma?

What stage is the disease? Did the patient present at a stage 3 or 4 disease? What type of lymphoma do they have? Do they have a T-cell lymphoma [which] tends to be more aggressive than a B cell? What is the age of the patient? When I was in Ohio, I took care of a patient he was 90 years old, maybe 91, but he was still working full time, he was playing golf every day, he had lymphoma and he wanted everything [treatment wise]. And he could take it because chronologically he was 92 [years], but he was more like 50 [years] because he would run around in circles around the nurses. I think it depends on the age of the patient and their comorbidities status. Do they have some renal failure or liver failure, are they a diabetic?

Those are things to consider, as well as asking the patients what they want. It’s hard to separate out sometimes what the patient [wants] and what the family wants. I think the stage of the disease, their comorbidities, the age of the patient, those are considerations for what type of treatment to go for. Now that we have oral drugs for lymphoma, those are a good option for [older] patients that may not want aggressive treatment.

Articles

Leslie Smith, DNP, RN, APRN-CNS, BMTCN, AOCNS, discusses new therapies and treatment selection in the lymphoma landscape.

Smith Discusses Evolving Landscape of Lymphoma Treatments 

Avelumab (Bavenzio), erdafitinib (Balversa), and enfortumab vedotin-ejfv (Padcev) are 3 distinctly different drugs which have recently been added to the fold of available urothelial cancer therapies, explains Laura Wood, RN, MSN, OCN.

®, she details nurse-specific considerations of these 3 agents.

“We [have] several new treatment options,” Wood says.“No. 1 is avelumab—which is approved as a maintenance therapy. It’s the first and only maintenance therapy approved for individuals with advanced or metastatic urothelial cancer that [has] not progressed with frontline platinum containing chemotherapy. Nurses need to be aware that this treatment is available, that it is an approved option for patients who are doing well and benefiting from first line platinum-based chemotherapy.”

In addition, nurses should know that patients will require premedication for the first 4 doses of avelumab, which is unique to the other approved immune checkpoint inhibitors, she adds.

“The second drug that I talked about was erdafitinib, and that is approved for locally advanced or metastatic urothelial cancer where there's an 

This means biomarker testing is necessary, she says. Further, the drug is linked to an increased risk of elevated phosphorous levels. Nurses should be cognizant of this and educate patients about this potential adverse event (AE)—and potentially educating them about a low phosphorus diet as well.

The drug also has a unique dosing titration. “We start that drug at 8 mg once daily, which is [two] 4-mg tablets. If patients, after 14 to 21 days, do not have increase in their phosphorus levels, or other significant grade to AEs including ocular AEs, that dose can be increased to 9 mg, which is a 3-mg tablet, and 3 tablets taken once daily.”

Educating the patient about the unique dosing regimen is important, she says.

Finally, Wood highlights enfortumab vedotin. The drug’s recommended dose is 1.25 mg/kg.

The maximum dose is 125 mg/kg. It is administered intravenously over 30 minutes on days 1, 8, and 15, as part of a 28-day cycle.

“It is an antibody-drug conjugate that targets nectin-4 on the cell surface of your affiliate cancer cells,” Wood explains. “The drug binds to the Nectin-4, is taken into the cell where the linker of the drug and the drug conjugate is dissolved, [then] the microtubule payload is released and that leads to cancer cell apoptosis and death.”

Enfortumab vedotin may induce severe and fatal cutaneous AEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These reactions frequently occur throughout the first treatment cycle but may also occur later.

Wood L. Novel approaches to renal and urothelial cancers. Presented at: 

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

Laura Wood discusses the successful integration of avelumab, erdafitinib, and enfortumab vedotin-ejfv into oncology nursing practice. 

Laura Wood on the Integration of Avelumab, Erdafitinib, and Enfortumab Vedotin into Urothelial Cancer Care

The growing availability of biomarkers has led to the advent of more targeted therapies such as the antibody-drug conjugates (ADCs) fam-trastuzumab deruxtecan-nxki (Enhertu), ado-trastuzumab emtansine (Kadcyla; T-DM1), and sacituzumab govitecan-hziy (Trodelvy). As treatments evolve, so too has the nurses’ role in understanding the nuances of sequencing and the safety and efficacy signals of each agent.

“Nurses spend a lot of time with patients and discuss what the oncologist has explained. Understanding the role of biomarkers and how that information is needed so we can make the best recommendation [is important],” Kimberly Podsada, MSN, NP-C, said. “[It is also important to] keep an open line of communication with the oncologist as well, as far as what other markers we might be testing for and staying up to date about these markers because it is a growing field. There have been a stream of new therapies and that has been exciting for us especially over the last few years in breast oncology.”



®, Podsada, a nurse practitioner at University of California San Diego Health in California, discussed the significance of using ADCs in an earlier line of therapy. She also highlighted how advances with oral selective estrogen receptor degraders (SERDs) are giving patients more options and how the integration of new agents is changing the treatment landscape.

How has the role of biomarker testing influenced emerging treatment considerations for patients with breast cancer?

Biomarkers have [become] more available and there are plenty of targeted therapies now because of these additional biomarkers. We are looking at biomarkers that go beyond the estrogen receptor, the progesterone receptor, and the HER2 receptor. Nowadays, we’re also looking at PD-1, PD-L1, the 

 positivity. There are many more markers now that help us to decide [on] treatments for women [in the] adjuvant and metastatic settings.

What are some agents that could challenge existing standards of care or be integrated into the treatment landscape?

In my lifetime in oncology, I have seen a couple of therapies come around that have really changed the treatment landscape, especially for HER2-positive disease. I was a part of the T-DM1 clinical trials when that came to market for the metastatic setting.

Now being a part of the DESTINY-Breast trials, the thing that has really changed the treatment landscape is the DESTINY-Breast03 [NCT03529110] information where trastuzumab deruxtecanhas now bumped T-DM1 for second line. This changes the treatment landscape, especially [in terms of] the median progression-free survival [PFS]. [The median PFS] has not been reached yet.

I am excited to see what happens now when people start using it in the second line of therapy in the metastatic setting.

We also have tucatinib [Tukysa], which is a tyrosine kinase inhibitor [TKI], for metastatic HER2-positive disease. That was an exciting clinical trial [HER2CLIMB trial (NCT02614794)] because it was the first trial that looked at patients with active brain metastases. Usually in a clinical trial, you can see stable brain metastases, but they allowed [individuals] on trial who had new, progressing, and active brain metastases. The TKI displayed a benefit in preventing new lesions from occurring and affecting what we are imagining.

How has the recent influx of approved therapies for patients with HER2-positive metastatic disease affected your practice and how are you addressing sequencing questions?

The sequencing question is always going to be out there. I look at it as we have a lot of tremendous options now for women with HER2-positive disease; T-DM1 in the adjuvant setting, trastuzumab deruxtecan in an earlier line setting for metastatic breast cancer patients, and tucatinib.

Some of it for me is based on conversations with the patient. What are their symptoms? What do they desire, as far as maybe a more oral driven therapy vs an infusion therapy? [Because of] some of the recent approvals, the sequencing will change again with trastuzumab deruxtecan now being able to be used earlier.

As far as what we now do after a second line, I [would say] move on to something like tucatinib as the following therapy, follow guidelines, and figure out the plan in collaboration with your patient because they are the one that is showing up and doing the hard work.

Can you speak to advances with novel medications, such as oral SERDs, for patients with ESR1 mutations?

This is going to be great for patients. Currently, we have an intramuscular injection, fulvestrant [Faslodex], and being able to take something by mouth instead of getting these very large injections will make patients very happy. We are seeing some promising research studies and, although it is still in clinical trials, this is another game changer.

There are always mixed thoughts about someone coming into the clinic or doing their treatment at home. [If they come into the clinic] we know they take their injections and their medicine. At the same time, that causes anxiety and stress because when [an individual] gets injections, they get anxious, and their blood pressure goes up.

If we had an oral version of it, many of us would start with the oral therapy first and I believe we are going to be seeing a couple of new oral SERDs coming to market which will be exciting and give us more options.

How are ADCs reshaping the treatment landscape for patients with TNBC?

ADCs are changing the treatment landscape for all breast cancer types. Trastuzumab deruxtecan and T-DM1, have had some of the biggest positive impacts on the breast cancer world.

In the triple-negative world, which is still an area that I want to see more research go into, it is the most challenging type of breast cancer to treat. We are continuing to come up with new methods of treating it including with ADCs.

Sacituzumab govitecan, has been approved and that is tremendous news for patients and providers to have another option for triple-negative disease. I would like to see some [approved agents] moved up into an earlier line setting—we will have to continue doing clinical trials for that.

There are [AEs] with these medications and a lot of times when some of these drugs are getting approved, they are given to people that have already been heavily pretreated. We are giving these women everything possible.

I’m also curious about what will happen to sequencing over time in the triple negative [space] when [we can start to use] any of these [agents] that are showing great efficacy and potency in an earlier line setting.We are getting there [and] we are making strides to get new therapies out there for triple-negative disease.

We are just trying to give a lot of these patients [better] quality of life as well as [improved] OS. I want women to live longer with their disease, but I also want it to be tolerable for them.

The growing availability of biomarkers has led to the advent of more targeted therapies such as the antibody-drug conjugates (ADCs) fam-trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, and sacituzumab govitecan-hziy. 

Podsada Discusses Biomarker Testing and ADC Therapies in Breast Cancer 

 met with Stephanie Jackson, DNP, MSN, RN, AOCNP, BMTCN, to discuss key takeaways from her recent presentation at the 

. Jackson, who is a certified oncology and bone marrow transplant clinical nurse specialist and unit director at UCLA Medical Center, presented on advances in the treatment of leukemia, and highlighted how nurses can practice at the top of their licensure incorporating the latest advances in hematologic malignancies.

Jackson discusses the clinical application of drugs which were recently added into the treatment schema, such as ivosidenib (Tibsovo) plus azacitidine, which was approved in May 2022 for patients with newly diagnosed 

-mutated acute myeloid leukemia (AML) who are aged 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. According to Jackson, differentiation syndrome and QT prolongation are 2 possible adverse events (AEs) associated with this treatment that nurses need to recognize.

She also discusses the evolving role of CAR T-cell therapy in the context of leukemia treatment, including the 2021 approval of brexucabtagene autoleucel (Tecartus) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Jackson highlights the benefits and limitations of this therapy, and offers a perspective on the potential benefit that allogeneic CAR T-cells may bring to the table.

Overall, it is inspiring time to work in leukemia, Jackson says.

“I’m excited about seeing many of my patients living much longer and being able to have treatments like CAR T,” she remarks. “It takes a nurse who is knowledgeable of the drugs, knows the AEs, and who are partnering with the interdisciplinary team to make sure that we can get these patients through this treatment.”

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Stephanie Jackson, DNP, MSN, RN, AOCNP, BMTCN, discusses the trajectory of targeted and CAR T-cell therapies such as ivosidenib and brexucabtagene autoleucel, and what nurses need to know about these treatments to be able to practice at the top of their licensure.

Stephanie Jackson Unpacks Recent Advances in Leukemia Treatments

New targeted therapies, immunotherapies, and antibody-drug conjugates for the treatment of urothelial cancer (UC) have accentuated the importance of the oncology nurse’s role in patient education and symptom management, according to Laura Wood, MSN, RN, OCN.

“Nurses play a critical role in providing education to patients and caregivers,” Wood said in an interview with 

, “ensuring that AEs [adverse effects] and irAEs [immune-related AEs] are identified early so appropriate interventions can be initiated, while…provid[ing] emotional support [to patients] as they navigate the cancer journey.”

A former oncology nurse specialist at the Taussig Cancer Center, Wood summarized what she had said at the 

 about avelumab (Bavencio), erdafitinib (Balversa), and enfortumab vedotin-ejfv (Padcev), underscoring their uniqueness and the best ways to manage their AEs.

Avelumab is the current standard of care maintenance treatment for patients with locally advanced or metastatic UC that has not progressed with frontline platinum-based chemotherapy. The drug was approved for patients who have received prior treatment with at least 1 line of platinum-based chemotherapy. Approval was granted based on 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% for 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 premedication 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 (NCCN) guidelines suggest that patients with locally advanced or metastatic disease who are cisplatin-eligible receive cisplatin-based combination chemotherapy followed by avelumab maintenance therapy or dose-dense methotrexate, vinblastine, doxorubicin, and 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 ineligible for 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). Alternatives to pembrolizumab include immune checkpoint inhibitors nivolumab (Opdivo) and avelumab and monotherapy with erdafitinib or enfortumab vedotin. Paclitaxel, docetaxel, and gemcitabine are also viable options included in the NCCN guidelines.

Depending on treatment history, the following sequential therapies may also be useful: ifosfamide, doxorubicin, and gemcitabine (IAG); gemcitabine/paclitaxel; gemcitabine/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.

To determine whether a patient is eligible for erdafitinib, the therascreen FGFR RGQ RT-PCR Kit or the formalin-fixed, paraffin-embedded (FFPE) test may be used.

“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.” What makes the medication unique, she added, is that with it “there is the potential for dose titration.”

The starting dose for erdafitinib is 8 mg once daily (two 4-mg tablets). After patients have been taking erdafitinib for 14 to 21 days, the dose may be increased to 9 mg daily (three 3 mg tablets) provided that patients can tolerate it and their serum phosphate levels are normal.

Nurses should note that erdafitinib 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…[and to] educate patients about a low-phosphorus diet.”

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 binder until levels are below 5.5 mg/dL.

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

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

The last drug Wood discussed was enfortumab vedotin. As she explained in the interview, the agent “is an antibody-drug conjugate [that] targets Nectin-4 protein on UC cells.” As it binds “with the Nectin-4 protein, the linker dissolves, and the microtubular payload is released, leading to cell cycle arrest and apoptosis,” she said.

The drug is indicated for adults with locally advanced or metastatic disease who have had previous PD-1 or PD-L1 inhibition and platinum-based chemotherapy. To be given enfortumab vedotin, patients must be ineligible for cisplatin-containing chemotherapy and must have received at least 1 prior line of therapy.

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

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

The drug also comes with a 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 told about the risk of infusion-site reactions, hyperglycemia, pneumonitis, and vision changes and advised to use artificial tears to prevent or treat dry eye. Moreover, baseline assessments and continued monitoring for peripheral neuropathy are advised.

According to Wood, a few investigative therapies with promising efficacy and safety profiles. One of them 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 was 71% (95% CI, 60.1%-80.5%). The median duration of response was 26.6 months, and the OS rate was 100% at a 2-year data cutoff.

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.

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

FDA granted accelerated approval to sacituzumab govitecan (Trodelvy)

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 of 3 prior lines of therapy, the objective response rate was 27%, and a measurable disease decrease was observed in 77%. Median PFS was 5.4 months, and median OS 10.9 months.

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

In her presentation Wood noted that nurses should encourage patient participation in clinical trials. She also urged nurses to give continued attention to biomarker testing in order to help facilitate potential clinical trial enrollment. 

 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. ImmunityBio. 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

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.

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

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. 

. 2019;380(12):1103-1115. doi:10.1056/NEJMoa1816047

Rini BI, Plimack ER, Stus V, et al; KEYNOTE-426 Investigators. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. 

. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714

Choueiri TK, Powles T, Burotto M, et al; CheckMate 9ER Investigators. Nivolumab plus cabozantinib 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. 

Annual School of Nursing Oncology

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Stephanie Jackson Unpacks Recent Advances in Leukemia Treatments

Approaches to Urothelial Care Call for Nuanced AE Management

Evolution of Frontline VEGF TKI/Immunotherapy Treatments Propels Field of Renal Cell Carcinoma

Molecular Profiling Is a Necessity in Colorectal Cancer Treatment

Paula Anastasia on PARP Inhibitor Ineligibility Factors for Women With Ovarian Cancer

Nurses Adapt to New Hematology Advances and Approvals in Leukemia Treatment