In August 2022, the relationship between nutrition and cancer was put to the test: myths surrounding sugar, soy, and vegan diets, and their ability to improve or injure patient outcomes were debunked. Similarly, the American Society of Clinical Oncology (ASCO) released updated guidelines with recommendations for diet and exercise for patients undergoing active treatment.

Oncology nurse research took center stage as new findings showed that taxane-based chemotherapy caused hearing loss in the majority of patients with breast, gastrointestinal, gynecological, or lung cancer. 

® discussed the findings and implications in clinical practice in an exclusive interview with principal investigator Christine Miaskowski, PhD, RN.

Finally, nurses play a powerful role in improving the quality of care for patients. Hear from experts how nurses can help ensure that patients with ovarian cancer receive optimized treatment plans, as well as help create an inclusive environment for all they attend to in their practice.

Dispelling Nutrition Myths for Patients With Cancer

Entering the words nutrition and cancer into Google returns as many as 718 million hits. With an overabundance of opinions, it can be challenging to separate fact from fiction. Therefore, in this feature, Nicole Franklin, MS, RDN, CSO, LDN, a registered dietician with the American Oncology Network, calls out 3 commonly held myths about nutrition and cancer and uncovers the bottom line.

Audiological Assessments May Be Vital Component of Cancer Survivorship Care Following Chemotherapy

New research efforts led Christine Miaskowski, PhD, RN, show that most adult cancer survivors who undergo treatment with either a platinum-based chemotherapy, taxane alone, or a combined regimen of platinum- and taxane-based treatment, experience some degree of hearing loss. In an interview with 

 Miaskowski, a professor in the Department of Physiological Nursing and Anesthesia at UCSF School of Nursing, highlights what these findings mean for clinical practice.

Nurses Play Key Role in Facilitating Maintenance Therapy With PARP Inhibitors in Ovarian Cancer

®, Paula Anastasia, RN, MN, AOCN, a gynecologic Oncology Clinical Nurse Specialist for UCLA Health, offers a recap of her presentation at 

. She discusses ways in which nurses can help facilitate maintenance therapy with PARP inhibitors such as olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula), and emphasizes the value of germline testing for this patient population.

ASCO Outlines Recommend Aerobic and Resistance Exercises for Patients Undergoing Active Cancer Treatment

ASCO recently convened a panel of experts to conduct a comprehensive literature review of existing data regarding the role of diet, weight, and exercise in defining patient outcomes. The updated guidelines formally recommend aerobic and resistance exercises for patient with cancer, although they note that this is an area of research that continues to be overlooked in clinical trial designs.

1. Addressing Disparities: Practicing Inclusion for LGBTQ+ Patients With Cancer

Identifying and acknowledging disparities helps providers work together to improve access to care and treatment and reduce the cancer risks. Among individuals in the LGBTQ+ community there is less access to care because of a lack of inclusive health care, underrepresentation and exclusions in clinical trials, and lack of coverage for appropriate screenings.

In this feature, our partners at Cancer Care outline key ways that nurses can improve their care delivery and create a practice that is inclusive for marginalized communities.

To stay on top of all the latest news and features

Articles

Each month, we take a look back at the most popular Oncology Nursing News® stories. Here are the top 5 stories from August 2022.

Oncology Nursing News Top Stories: August 2022

Most patients with unresectable or metastatic renal cell carcinoma (RCC) about to initiate VEGF tyrosine kinase inhibitor (TKI) therapy are prescribed a reduced dose, according to a retrospective chart review published in the 

Journal of Hematology Oncology Pharmacology.

 Moreover, study results indicate that a reduced TKI starting dose may improve therapy tolerability without compromising efficacy.

Among patients treated at the Georgia Cancer Center-Laney Walker campus who received a TKI between January 1, 2015, and June 30, 2020, 66.7% (n = 28) began therapy at a reduced dose and 33.3% (n = 14) began therapy at the full dose. No differences were observed in overall survival (OS; 

“Our study revealed that the majority of current patients at our institution are being started with a reduced dose of a TKI for the treatment of metastatic RCC,” the study authors wrote. “No differences were observed in overall survival or in the number of patients with dose reductions or treatment discontinuations between those who were started with a reduced-dose TKI and those who were started with a full-dose TKI. Similar to most previous reports, the lack of deleterious effect on patients’ outcomes further supports the use of an initial reduced-dose TKI strategy.”

Patients with relapsed or metastatic RCC regularly receive VEGF TKIs as first- or second-line therapy. Approved treatment options within this class of agents include sunitinib (Sutent), pazopanib (Votrient), cabozantinib (Cabometyx), lenvatinib (Lenvima), everolimus (Afinitor), and axitinib (Inlyta). Each of these treatments is associated with adverse events of any grade, which may lead to dose reductions, interruptions, or discontinuations. In the clinical trial setting, nearly 46% of patients will require a dose reduction because of an adverse event.

In light of this, ongoing research efforts are directed toward the dose optimization of TKIs. Previous research has examined the relationship between dose reductions and alternate dosing schedules and the relation with tolerability and efficacy. However, investigators at the Georgia Cancer Center sought to assess outcomes of patients who 

Collected patient data included baseline characteristics, history of immune checkpoint inhibitor therapy before or after TKI use, drug received, initial dose, start date, and the date and reasoning for dose reduction, temporary interruption, and/or treatment discontinuation.

The study’s primary end point was the percentage of patients who received first-line treatment with a TKI at a reduced dose. The secondary end point was the relationship between a reduced starting dose and duration of therapy, incidence of further reductions or interruptions, and OS. Any decrease in dose or frequency compared with the FDA indication was classified as a reduced dose.

The percentage of patients who died was 25% among those who began with a reduced dose and 42.9% among those who began with a full dose. The percentage was clinically different, but not statistically different. More than 50% of patients survived in each arm and as a result median survival and upper limit of 95% CI could not be estimated. The median time to death among these 2 groups was 20.1 months vs 25 months, respectively (


Most patients initiating with a reduced dose (78.5%; n = 22) were prescribed their treatment in 2017 or later and approximately 100% of patients (n = 14) receiving a full dose were prescribed their regimen prior to 2017. The median duration of treatment between these 2 groups was 6.6 months vs 13.9 months, respectively (

Many patients receiving frontline therapy required at least 1 intervention. Among those in the reduced-dose group, the percentage of patients requiring reductions and discontinuation were 47.8% (n = 11) and 82.6% (n = 19), respectively. In the full-dose group, the percentages were 55.6% (n = 5) and 100% (n = 9), respectively. In both groups, the most causes of dose reductions were adverse events and disease progression.

Stitt TM, Saunders KM, Rowling BC, Waller JL, Clemmons AB. Reduced starting dose of tyrosine kinase inhibitors in patients with metastatic renal-cell carcinoma

Starting patients with unresectable or metastatic renal cell carcinoma on a reduced dose of VEGF tyrosine kinase inhibitor (TKI) therapy did not compromise survival outcomes.

Reduced VEGF TKI Dose May Be Preferable in Treating Patients With Renal Cell Carcinoma

Phase 2 findings showed that rucaparib (Rubraca) may an effective maintenance option for patients with DNA repair–deficient (DRD)-positive, metastatic 

 whose disease has progressed following platinum-based chemotherapy. Findings from the ATLANTIS trial (ISRCTN25859465), which were published in the 

, showed that patients who received the PARP inhibitor achieved extended progression-free survival (PFS).

Twelve (60%) and 20 (100%) PFS events occurred among the 20 patients enrolled in the rucaparib and placebo arms, respectively. At a median follow-up of 94.6 weeks (range, 11.4-148.9) in patients still alive, the median PFS was 35.3 weeks (80% CI, 11.7-35.6) with rucaparib vs 15.1 weeks (80% CI, 11.9-22.6) with placebo (HR, 0.53; 80% CI, 0.30-0.92; one-sided 

“In this efficacy signal-seeking phase 2 trial, we found that switch maintenance treatment with rucaparib resulted in clinically meaningful improvement in the primary end point of PFS, despite small numbers,” lead study author Simon J. Crabb, PhD, MBBS, of Southampton Experimental Cancer Medicine Centre, and coauthors, wrote in the publication.

Platinum-based chemotherapy is the standard frontline treatment for patients with metastatic urothelial cancer, but disease progression remains an inevitable reality for almost all patients, and responses are difficult to salvage even with second-line therapy.

 has since become a standard of care following frontline chemotherapy, most patients will not benefit from immunotherapy, leaving an unmet need for molecularly-directed treatment approaches.

As such, investigators conceptualized the ATLANTIS trial, which is an adaptive, multicomparison, clinical trial platform. As part of this effort, investigators are evaluating several, biomarker-selected switch maintenance therapeutic approaches for patients with metastatic urothelial cancer without disease progression after completing 4 to 8 cycles of platinum-based chemotherapy in a series of parallel, randomized, double-blind, phase 2 comparisons.

To be eligible for enrollment within the rucaparib comparison, patients had to be at least 16 years of age and have a diagnosis of stage IV (stage T4b and/or N1-3 and/or M1), histologically confirmed, DRD-positive urothelial cancer ineligible for curative-intent treatment. Patients also had to have an ECOG performance status between 0 and 2 and were required to begin study treatment within 3 to 10 weeks of completing 4 to 8 cycles of first-line platinum-containing chemotherapy. Notably, patients were excluded for cancer progression during, or at completion of, first-line chemotherapy.

Patients were randomly assigned 1:1 to receive 600 mg of maintenance rucaparib twice a day orally, or placebo, until disease progression.

Patients were determined to be DRD positive if any of the following were present: at least 10% genome-wide loss of heterozygosity and/or alteration in a defined DRD associated gene (

ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D,

) and/or prior confirmation of a germline alteration in 

The primary end point of the trial was PFS. Statistical analysis targeted a hazard ratio of 0.5, with a 20% one-sided α. PFS, which was investigator assessed by RECIST v1.1 criteria, was compared between trial arms in the intention-to-treat (ITT) population, within a Cox model. Secondary end points included overall survival (OS), confirmed response rates, maximum percentage decrease in measurable disease, safety, and tolerability.

Out of 248 patients, 74 (29.8%) were DRD positive and 40 were randomly assigned.

Within the ITT population, the median age was 70.5 years (range, 53-86); 35 (87.5%) patients had a primary bladder cancer and 18 (45%) had visceral metastases. Twenty-five patients (62.5%) received prior cisplatin-based chemotherapy and 36 (90%) achieved an objective response to first-line chemotherapy.

Additional results demonstrated that 9 (45%) and 14 (70%) patients in the rucaparib and placebo arms, respectively, had died. The median OS was not reached in the rucaparib arm and 72.3 weeks (80% CI, 51.7-85.4) in the placebo arm (HR, 1.22; 80% CI, 0.62-2.38; 

One confirmed partial response occurred in one patient (5%) treated with rucaparib. No other objective radiologic responses to treatment occurred on study, in either treatment group. The maximal percentage reduction in measurable disease was comparable between treatment arms, with medians of −5.8% (interquartile range [IQR], −21.2-36.3) and −4.9% (IQR, −17.9-37.7) for rucaparib and placebo, respectively.

In the safety population (n = 39), treatment-related adverse effects (TRAEs) were mostly low grade. Patients received a median of 10 cycles of rucaparib and 6 cycles of placebo.

All-grade TRAEs of fatigue (63.2% vs 30.0%; 

 = .04), and raised alanine aminotransferase (57.9% vs 10%; 

 = .003) were more common in the rucaparib arm.

Five (26.3%) patients on rucaparib and 1 (5%) on placebo discontinued treatment because of treatment-related toxicity or patient decision. At least 1 dose reduction was required in 7 (36.8%) patients receiving rucaparib and 4 (20%) receiving placebo. No treatment-related deaths occurred.

The additional toxicity linked with treatment was consistent with previous experience for PARP inhibition, and rucaparib specifically, according to the study authors.

“Further development of PARP inhibition in metastatic urothelial cancer is now warranted,” the authors concluded. “This may require combination strategies and will require further scrutiny of patient genomic phenotypes to optimally integrate into the increasingly complex treatment pathway for this disease.”

Crabb SJ, Hussain S, Soulis E, et al. A randomized, double-blind, biomarker-selected, phase II clinical trial of maintenance poly ADP-ribose polymerase inhibition with rucaparib following chemotherapy for metastatic urothelial carcinoma. 

. Published online August 12, 2022. doi:10.1200/JCO.22.00405

Rucaparib may be a viable maintenance therapy option for patients with DNA repair–deficient positive, metastatic urothelial cancer who are unlikely to benefit from avelumab immunotherapy. 

Patients With DRD+ Metastatic Urothelial Cancer Achieve Prolonged PFS with Rucaparib Maintenance Therapy 

A regimen of olaparib (Lynparza) plus abiraterone and prednisone or prednisolone has received priority review status for the indication of metastatic castration-resistant prostate cancer (mCRPC).

 Under the Prescription Drug User Fee Act date, the regulatory decision is anticipated by the final quarter of 2022.

The supplemental New Drug Application (sNDA) is supported by data from 

 (NCT03732820), which were presented at the 2022 ASCO GU Cancers Symposium

 The findings showed that the experimental combination reduced the risk of disease progression or death by 34% compared with abiraterone alone (HR, 0.66; 95% CI, 0.54-0.81; 

 < .0001), which was statistically significant and clinically meaningful.

“This benefit led to what I think is the longest [radiographic progression-free survival] rPFS we have seen to date in mCRPC beyond 2 years,” Fred Saad, MD, FRCS, professor and chairman of urology and director of Genitourinary Oncology at the University of Montreal Hospital Center, as well as the Raymond Garneau Chair in Prostate Cancer Research and director of Clinical Research and the Molecular Oncology Research Laboratory in Prostate Cancer, remarked in a presentation of the phase 3 findings.

The median rPFS in the olaparib arm was 24.8 months, compared with 16.6 months in the abiraterone as monotherapy arm. Moreover, the safety and tolerability of the regimen was reported to be similar the previous clinical trials findings and the known profiles of the individual medicines.

The PROpel trial randomly assigned patients 1:1 to receive either a twice daily 300 mg dose of olaparib, or placebo, in addition to a once daily 1000 mg dose of abiraterone. All patients were given two daily dose 5 mg doses of prednisone or prednisolone mg per the abiraterone label requirement. Treatment continued until disease progression, intolerable toxicity, or withdrawn consent. In the event of disease progression, further treatment decisions were based on investigator discretion.

In the United States, prostate cancer represents the second most common cancer in males is expected to cause approximately 35,000 deaths in 2022. In the clinical trial setting, the overall survival for patients with mCRPC is approximately 3 years. This rate is shorter in the real world. About half of patients with mCRPC will receive only 1 line of active treatment, with subsequent therapies offering a diminished benefit.

Previous research efforts have demonstrated encouraging results with the PARP inhibitor in the mCRPC setting. Phase 2 (NCT01972217) findings have revealed the combination of olaparib and abiraterone prolonged investigator-assessed rPFS vs placebo/abiraterone following treatment with docetaxel, regardless of HRR status (HR, 0.65; 95% CI, 0.44-0.97; 

approved for patients with mCRPC with an HRR gene mutation

 (including a BRCA-mutation) whose disease has progressed following prior treatments with enzalutamide or abiraterone since May 2020, based on positive findings from the phase 3 PROfound trial.

 With this most recent priority review, the FDA will now determine if the same benefit can be derived for patients regardless of their HRR gene mutation status.

“There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited,” Susan Galbraith, executive vice president of Oncology R&D, at AstraZeneca, concluded in a press release. “Today’s news is another step toward bringing forward a new, much-needed treatment option in this setting.”

Lynparza in combination with abiraterone granted priority review in the US for patients with metastatic castration-resistant prostate cancer. News release. AstraZeneca. August 16, 2022. Accessed August 16, 2022. 

Saad F, Armstrong AJ, Thiery-Vuillemin A, et al. PROpel: phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). 

. 2022;40(suppl 6):11. doi:10.1200/JCO.2022.40.6_suppl.011.

Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. 

. Published online June 3, 2022. doi:10.1056/EVIDoa2200043

Clarke N, Wiechno P, Alekseev B, et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. 

. 2018;19(7):975-986. doi:10.1016/S1470-2045(18)30365-6.

Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. 

. 2020;383(24):2345-2357. doi:10.1056/NEJMoa2022485.

Lynparza approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. Published May 20, 2020. https://bit.ly/36eCJlP. Accessed May 20, 2020.

The FDA has granted olaparib plus abiraterone priority review status for the indication of metastatic castration-resistant prostate cancer.

Olaparib/Abiraterone Combo Undergoes Priority Review for mCRPC Indication 

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.

Videos

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

Patients actively receiving cancer treatment are encouraged to engage in aerobic and resistance exercises to alleviate treatment-related toxicities and improve quality of life, according to a new guideline published by ASCO.

The updated guideline follows a literature analysis of 52 systematic reviews on the topics of exercise, died, and weight management, and results of 23 randomized clinical trials. Each of the selections underscored the value that exercise interventions may interpose on patients receiving either systemic therapy, radiation, or surgery.

Of note, this guideline represents the first of its kind to specifically focus on patients who are actively receiving treatment. It is intended for oncology professionals and designed to provide evidence-based recommendations for optimized treatment tolerance, quality of life, and cancer control outcomes.

Recommendation No. 1: Aerobic and Resistance Exercises

Oncology providers should encourage patients on active treatment to incorporate aerobic and resistance exercises to mitigate treatment-related adverse events (AEs).

Aerobic and resistance exercises have the potential to reduce fatigue, preserve cardiorespiratory fitness, physical functioning, and strength. In some populations, the benefits reach further; they may maintain or improve quality of life as well as help reduce anxiety and depression. Moreover, these interventions have a low risk of AEs.

It is important to note that although ASCO labeled this as a strong recommendation in the outline, the evidence quality is still moderate to low, and the benefits are not intended to extend to overall treatment outcomes or completion rates but instead are centered on improving life quality throughout treatment.

The authors of the guideline noted that prehabilitation is an emerging field but that oncology providers may consider encouraging patients about to undergo lung surgery to initiate preoperative exercises. This intervention is intended to reduce length of hospital stay and postoperative complications and had the strongest evidence compared with other tumor types included in the analysis.

As with the first part of this recommendation, the evidence has shown that the benefit of exercise outweighs the risks in this setting; however, the recommendation strength was listed as “weak” by ASCO because evidence quality was low and randomized control trials are warranted.

According to the study authors, there is insufficient evidence to either recommend or condone specific diets such as ketogenic, low-carbohydrate, or low-fat diets. Similarly, functional foods and fasting have not been sufficiently linked to improved outcomes in quality of life, treatment toxicity, or disease control.

That said, neutropenic diets are not recommended. These diets specifically exclude raw fruits and vegetables, and they have not been shown to prevent infection in patients undergoing active treatment. This recommendation is evidence based and the authors note that the harms are likely to outweigh the benefits. However, according to ASCO, the evidence quality is low.

Recommendation No. 3: Weight Loss and Weight Gain

The expert panel strongly feels that there should be more research centered in this domain.

There is insufficient evidence tying intentional weight loss or weight gain interventions to quality of life, treatment toxicity, or cancer control outcomes. Despite this, the ASCO expert panel expressed that these are critical areas that provide health benefits to the general population, and therefore may also provide important benefits to patients with cancer.

Despite the lack of guidance underscored in the outline, authors note that dietary change and weight management strategies may still be valuable during or after cancer treatment. Further, a recent ASCO survey of over 2419 patients throughout the United States found that nearly 75% of patients make changes in their diet or exercise patterns following diagnosis.

In addition, the guideline stated that a lack of guidance does not equate to support of a diet filled with red meats and processed foods or carbohydrates; providers are still encouraged to discuss healthy diet and weight with their patients, but no specific recommendations are endorsed by the 2022 ASCO guideline.

According to the panel, there are numerous areas where research can be expanded to provide more concise consul to oncology professionals.

One such area is for individuals with advanced cancer. These individuals are often excluded from these trials because of concerns regarding the safety of such interventions‚ especially in patients with bone metastases. The guideline experts looked at a literature review which assessed 17 studies looking at patients with bone metastases. Although results were largely mixed, the findings suggested that there may be exercise benefit for these patients.

Moreover, the experts encourage investigators to consider incorporating diet, exercise, and weight assessments into routine clinical research. According to the authors, this guideline highlighted a profound gap in quality research in this area, yet 

many opportunities exist at modest overall cost, to integrate validated and novel assessment tools of diet, nutritional status, and exercise into clinical trials, such as body composition assessment including fat distribution and lean muscle mass, use of enhanced statistical tools to analyze dietary patterns, use of wearables to capture physical activity, and validated fitness tests such as the [6-minute walking test] 6MWT.”

Moving forward, phase 1, 2, and 3 findings assessing diet, exercise, and weight management interventions will be needed across the care continuum to define the standards of care in this field.

Ligibel JA, Bohlke K, May AM, et al. Exercise, diet, and weight management during cancer treatment: ASCO guideline. 

. 2022;40(22):2491-2507. doi:10.1200/JCO.22.00687

An ASCO expert panel conducted a comprehensive literature assessment to determine how diet, weight, and exercise play a role in defining patient outcomes.

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

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.

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.

Genitourinary Cancer