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

Articles

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. 

. 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. 

. 2021;384(9):829-841. doi:10.1056/NEJMoa2026982

Wood LS, Ornstein MC. Toxicity management of front-Line pembrolizumab combined with axitinib in clear cell metastatic renal cell carcinoma: a case study approach. 

. 2020;16(suppl 2):15s-19s. doi:10.1200/JOP.19.00647

Ryan CW, Tangen C, Heath EI, et al. EVEREST: everolimus for renal cancer ensuing surgical therapy—a phase III study (SWOG S0931, NCT01120249). 

. 2022;40 (suppl 17):LBA4500. doi:10.1200/JCO.2022.40.17_suppl.LBA4500

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. 

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

Darolutamide tablets (Nubeqa), in combination with docetaxel, have been approved for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

The FDA approval was primarily supported by efficacy data from the ARASENS trial (NCT02799602), a multicenter, double-blind, placebo-controlled clinical trial, in which 1306 patients were randomly assigned to receive 600 mg of oral darolutamide once daily in addition to 75 mg/m2 intravenously administered docetaxel or placebo plus docetaxel. All participants received a concurrent gonadotropin-releasing hormone analog or a bilateral orchiectomy.

Overall survival (OS) represented the primary end point and the median OS was not reached (NR) (95% CI, NR-NR) in the experimental arm vs 48.9 months (95% CI, 44.4-NR) in the control arm (HR 0.68; 95% CI, 0.57-0.80; 

< .0001). Moreover, time-to-pain progression, a secondary end point, was also significantly improved by the addition of darolutamide to docetaxel (HR 0.79; 95% CI, 0.66-0.95; 1-sided

The median age of patients was 67 years (range, 41-89), with 17% of patients at least 75 years. Moreover, 52% of patients were White, 36% were Asian, 4% were Black or African American, and 7% were Hispanic/Latino. Three percent of patients had M1a disease, defined as having spread to distant lymph nodes, 83% had M1b, defined as having spread to the bones, and 14% had M1c, defined as having spread to organs.

The trial defined a common adverse event (AE) as one that occurred in over 10% of patients receiving darolutamide with a greater incidence of at least 2% than with placebo. These AEs included decreased appetite, rash, hemorrhage, increased weight, and hypertension. Furthermore, laboratory test abnormalities were classified as common if they occurred in 30% or more patients, and included anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.

 Two tablets should be taken twice daily with food. Tablets must be swallowed whole. Docetaxel is to be administered intravenously on a 21-day cycle for up to 6 cycles at a dose of 75 mg/m2. The cycles should be initiated within 6 weeks of the first darolutamide treatment. Patients on this treatment regimen should also be receiving either a gonadotropin-releasing hormone analog or a bilateral orchiectomy. If a patient forgets a daily dose, they are to take their missed dose as soon as they remember and prior to the next scheduled dose, and not to take 2 doses together at the same time.

For patients with severe renal or hepatic impairment, the recommended dose is 300 mg twice daily.

Darolutamide has been associated with an increased risk of ischemic heart disease, seizure, and embryo-fetal toxicity. Prior to treatment patients should be counselled on these risks and taught to inform providers of any related symptoms immediately and to use effective contraception. Darolutamide may also pose a risk to a patient’s fertility.

FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. FDA. August 5, 2022. Accessed August 5, 2022. https://bit.ly/3SqCCLw

Nubeqa. Prescribing information. Bayer HealthCare Pharmaceuticals Inc; 2022. Accessed August 5, 2022. 

Patients with hormone-sensitive prostate cancer who received darolutamide in combination with docetaxel experienced superior overall survival and time-to-pain progression benefit. 

FDA Approves Darolutamide Tablets for Select Patients With Prostate Cancer

Each month, we take a look back at the most popular 

Topics from July 2022 include key advances in cancer survivorship toxicity management and efforts towards targeting 

mutations in the treatment paradigm for patients with pancreatic cancer. Additionally, recently reported data showed the potential quality-of-life benefit observed with ribociclib (Kisqali) for patients with hormone receptor–positive, HER2-negative breast cancer.

Other top stories include an interview with Gretchen McNally PhD, ANP-BC, AOCNP, on the need for naloxone training for oncology nurses and advanced practice providers (APPs) and a conversation between 2 palliative care experts on why buprenorphine should be considered for the treatment of cancer-related pain.

5. Frontline Ribociclib-Related Quality of Life Favorable to Abemaciclib in HR+/HER2-Advanced Breast Cance

Ribociclib was favorable over abemaciclib (Verzenio) in reducing diarrhea, fatigue, appetite loss, and arm symptoms (such as pain or swelling in the shoulder or arm and difficulty raising the arm), according to a matched-adjusted indirect comparison using published data from individual patients treated in the MONALEESA-2 (NCT01958021) and MONARCH-3 trials (NCT02246621).

4. Targeting KRAS Mutations May Help Address Unmet Need in Pancreatic Cancer Treatment

In recent years, the identification of genetic mutations such as 

 in pancreatic cancer has shifted the treatment landscape toward targeted therapies. Despite this progress, combination chemotherapy remains the standard frontline treatment for patients with localized or advanced disease. Today, many investigators are turning their eye to 

 mutations, as these mutations are the most common genetic alterations for patients with pancreatic cancer and may represent a viable treatment landscape, according to Philip A. Philip, MD, PhD, FRCP.

3. Key Advances in Cancer Survivorship Toxicity Management

, Lidia Schapira, MD, FASCO, highlights from the 2022 ASCO Symptoms and Survivorship track anddiscusses key advances in the treatment of toxicities that may present later in cancer survivorship care. She discusses the importance of baseline measurements and health equity considerations in clinical practice and underscores the potential effect evolving technologies may have on the treatment landscape.

2. Are Oncology Nurses Underutilized in Positively Affecting the Opioid Epidemic?

a nurse practitioner in hematology at The Ohio State University Comprehensive Cancer Center– Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, discusses how oncology nurses might have the opportunity to save more lives with proper naloxone training. Responses obtained from nurses and APPs at McNally’s institution demonstrated that they would feel comfortable administering naloxone, provided they had the proper training, and would be interested in pursuing educational trainings on the agent

1. Experts Make the Case for Buprenorphine Use in Cancer-Related Pain Management

At the Annual Meeting on Supportive Care in Cancer, Mary Lynn McPherson, PharmD, BCPS, FAAHPM, and Amy A. Case, MD, FAAHPM, argued that buprenorphine should play a larger role in cancer-related pain management because of its unique pharmacology and consequent safety profile. As a partial agonist, buprenorphine has less μ-receptor signaling, which may result in fewer opioid-related adverse events. However, this does not mean buprenorphine is not an effective analgesic. It has a higher binding affinity compared with most full μ-opioid agonists, suggesting that it is a very effective pain management option.

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


Oncology Nursing News Top Stories: July 2022

Recommendations for the use of liquid biopsies to detect circulating tumor DNA (ctDNA) were recently released by the European Society for Medical Oncology (ESMO). Investigators reviewed available evidence to provide tumor-specific and general consensus on the use of ctDNA and clarify quality standards required for decision-making.

The assay, which is minimally invasive and can provide more convenient and rapid results compared with tissue samples, has become increasingly used in clinical practice to molecularly profile tumors. The release of ctDNA is believed to be proportional to tumor growth with more ctDNA being shed as a tumor grows.

In early-stage cancers, ctDNA has a role in screening, neoadjuvant monitoring, identification of molecular residual disease (MRD), molecular relapse monitoring, and early assessment of treatment response. Of note, the guideline authors state there is a lack of clinical evidence to support the recommendation of ctDNA assays in these areas.

“New technologies currently in development, such as methylation pattern-based sequencing, fragmentation pattern-based sequencing or novel ultra-sensitive mutation detection methods, have the potential to optimize utility in these new settings,” the study authors wrote. “Multiple clinical trials are underway that may provide the evidence base to adopt ctDNA assays for decision making in multiple clinical scenarios.”

However, ctDNA assays have a larger role for patients with advanced disease as it can be used to guide adoptive adjuvant strategies upon clinical relapse, identify biomarkers to guide therapy and monitor response to therapy, and, upon disease progression, ctDNA assays can be used to identify acquired resistance mechanisms and the emergence of driver and resistance clones.

The evaluation of ctDNA varies and a single ctDNA assessment is fit for all purposes. Investigators noted that the ctDNA fraction changes based on tumor features such as extent of necrosis, disease burden, tumor location, inflammation, rates of proliferation and apoptosis, tumor microenvironment and host-related phenomena. Treatments such as chemotherapy, targeted therapy, radiation, and immunotherapy can also affect levels of ctDNA and ctDNA fraction.

Liquid genotyping consists of polymerase chain reaction (PCR)-based technologies and many studies have shown positive predictive values between ctDNA liquid biopsy and tissue-based PCR and next-generation sequencing testing in advanced malignancies (95%-99%). High accuracy of liquid biopsy in breast, gastrointestinal and lung cancer for single-nucleotide variants have been reported in large prospective studies of liquid biopsy.

The ESMO guidelines include tumor-specific recommendations for tier 1 and tier 2 variants across tumor types including the following:

 ctDNA genotyping recommended in treatment-naïve patients with cancer with resistance to prior TKIs. ctDNA testing may not have adequate sensitivity to detect 

 true high copy number gain as resistance mechanism to osimertinib (Tagrisso) or lorlatinib (Lorbrena). Further, amplification and fusion detection is suboptimal with ctDNA assays, and should be repeated in tissue where possible.

mutations should preferentially be tested in ctDNA. 

fusions only when advanced tissue biopsy not available.

 ctDNA testing if tissue not available or when fast turnaround time is needed for urgent therapeutic decision-making.

 V600E/microsattelite instability for chemotherapy-naïve metastatic colorectal cancer is recommended when tissue testing is not feasible or urgent therapeutic decision-making. 

 pathogenic or likely pathogenic somatic variants may be carried out if tissue not available.

 for potential PARP inhibitor therapy. Caution is needed when interpreting results of ctDNA assays due to false-positive CHIP mutations in DNA repair genes.

Pancreatic, hepatocellular, endometrial, urothelial, thyroid, and soft tissue sarcoma

In terms of general tumor site recommendations, the ESMO guideline committee noted the occasions where tissue testing may provide confirmatory or more accurate guidance for treatment decision-making. These include interpretation of pathogenic variants such as 

; retesing results that are deemed “not detected” by ctDNA; and for the detection of fusions and copy number events. Further, liquid biopsy should not be taken when a tumor is responding to treatment.

Liquid biopsy may have limitations for the detection of specific deviations, and they risk false negative results and the authors recommend that clinicians take these into consideration when evaluating the results. A false negative result may occur when a patient’s plasma sample does not have sufficient levels of ctDNA or ‘non-shedding’ happens, preventing the detection of a variant. False positive results may occur when clonal expansion takes place in apoptotic hematopoietic cells, where plasma DNA mainly originates; the frequency of clonal hematopoiesis of indeterminate potential (CHIP) increases with age, previous systemic cancer treatment and smoking. False positives can be minimized with either the sequencing of white blood cell DNA or the pairing sequencing of a tumor tissue sample. Additional limitations of ctDNA testing include a low tumor fraction presence in the sample, which prevents reliable assessment of variant allele fraction and limits copy number alteration analysis.

The guidelines recommend that clinicians consult a molecular tumor board for to assess results.

Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. 

. Published online July 6, 2022. doi:10.1016/j.annonc.2022.05.520

In early-stage cancers, ctDNA has a role in screening, neoadjuvant monitoring, identification of molecular residual disease (MRD), molecular relapse monitoring, and early assessment of treatment response.



ESMO Guideline on Liquid Biopsy Address Quality Standards for Clinical Implementation

The combination of mental, physical, and emotional toxicities of cancer treatment result in a very large burden for patients, according to Lidia Schapira, MD, FASCO. Therefore, finding innovative strategies to improve supportive care and symptom management should be top of mind for all practicing oncology providers.

Schapira, who is a professor of medicine, and director of the Cancer Survivorship Program, at Stanford University, met with 

® to discuss key takeaways from this year’s Symptoms and Survivors’ track at the 2022 ASCO Annual meeting. Schapira’s clinical research is focused on the psychosocial aspects of cancer care and issues that relate to patient experience and health equity, and she participated on the track as an invited speaker in a poster discussion session.

One key takeaway from the session is the value of uniform baseline measurements in clinical practice, she said.

“Having good baseline measurements in clinical practice, and of course, in research, is essential, especially in the field of symptom management,” she told 

®, explaining that a great example of this was an ASCO presentation on vitamin D insufficiency-related peripheral neuropathy which compared the clinician assessment and patient reported assessment of neuropathy.

In this study, participants were evaluated at baseline for 25-OH-vitamin D (D2 + D3) via LC-MS assay. Investigators used logistic regression to identify the association between vitamin D insufficiency and grade 3 or greater sensory neurotoxicity. Vitamin D insufficiency was defined as 20 ng/mL with higher levels signifying vitamin D sufficient status.

Results were adjusted for paclitaxel regimen assignment, age, self-reported race, and body mass index and found that the rate of grade 3/4 chemotherapy-induced peripheral neuropathy (CIPN) was 21% (n = 397) among patients with sufficient status compared with 14% (n = 794) among those with vitamin D insufficiency (odds ratio [OR], 1.57; 95% CI, 1.14-1.15; 

= .005). After adjusting for covariates, the odds ratio was 1.39 (95% CI, 0.98-1.97; 

“Neuropathy is one symptom that has—for decades—been very difficult for us to properly measure,” Schapira said. “The importance of this is that if we don’t quite understand just how much toxicity somebody is experiencing, we could overdose them and [induce] irreparable harm.”

Lidia Schapira, MD, FASCO, discusses the importance of rigorous baseline measurement in improving the assessment and management of distressful cancer symptoms.

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Approaches to Urothelial Care Call for Nuanced AE Management

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

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

FDA Approves Darolutamide Tablets for Select Patients With Prostate Cancer

Oncology Nursing News Top Stories: July 2022

ESMO Guideline on Liquid Biopsy Address Quality Standards for Clinical Implementation

Uniform Baseline Measurements Are Crucial in Improving Standard of Supportive Care

Key Advances in Cancer Survivorship Toxicity Management

Burbage Provides Nursing Perspective on 2022 ASCO Meeting

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