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

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

Colorectal cancer (CRC) is the most common cancer in the United States, and is the second most common cause of cancer-related death.

 However, molecular testing is drastically changing the treatment landscape and improving patient outcomes in this specialty, according to Kelley A. Rone, DNP, RN, ADNP-C.

“One of the things that is most relevant is the molecular profiling portion of cancer in general. [But] it's such a rapidly changing part of oncology, that it is sometimes hard to keep up,” Rone, who is an advanced practice nurse specializing in [gastrointestinal] GI cancers at Mayo Clinic in Phoenix, Arizona, said in an interview with 

 “As new mutations become recognized and become linked to certain treatments, that is going to change a lot of the way treatments are matched.”

Rone recently presented on advances in gastrointestinal cancers as part of the 

. In her talk, she highlighted the various biomarkers that patients with colorectal cancer should be tested for, and the corresponding treatment options.

“It is important for the nurses to understand the importance of testing,” Rone told 

®, noting that nurses can be critical in ensuring that the appropriate tests have been ordered for different patients.

“If someone comes in and [we do not believe their cancer is] metastatic, or if the have had their prior biopsy done at an outside institution, we may not necessarily think about doing the molecular profiling. [But] sometimes myself or the clinic nurses will say to the physician: Did we do molecular profiling on this patient? Because if it hasn’t been done, we can order it,” she said.

Mismatch repair deficiency (dMMR) and microsatellite stability testing is recommended for all patients with newly diagnosed colon cancer, regardless of disease stage.

 In addition, patients with metastatic disease should be screened for 

 mutations are the most frequently mutated oncogenes and these variants are present in 90% of pancreatic cancers, 45% of colon cancers, and 35% of lung cancers. 

prior to initiating any EGFR-inhibiting therapy, such as cetuximab (Erbitux) or panitumumab (Vectibix). Patients who present with 

mutations (1.7%) should not receive anti-EGFR therapy, as these biomarkers have negative predictive value with these therapies.

 mutations, as they serve as the primary effector of 

signaling. These mutations are most likely to occur in exon 15 (V600E). Identified in approximately 10% of patients with CRC, 

mutations. If a molecular profile comes back as 

Approximately 2% to 3% of patients with CRC will show a degree of 

 amplification is increased; approximately 5% of these patients will have this amplification. Uncommon among patients with 

 amplification is frequently associated with left-sided CRC. Identifying this amplification is key in determining if a patient may benefit form a HER2-directed therapy.

As of August 2022, patients with metastatic disease may receive a combination of bevacizumab (Avastin) plus either FOLFOX,

 FOLFIRI, or FOLFOXIRI. They may also receive any of these chemotherapies as monotherapy.

 mutations) left-sided tumors may receive monotherapy with cetuximab

or panitumumab. They also may receive one of the anti-EGFR therapies in addition to chemotherapy (FOLFOX or FOLFIRI).

Patients with dMMR and microsatellite instability–high disease are eligible for monotherapy with pembrolizumab (Keytruda), nivolumab (Opdivo), or ipilimumab (Yervoy). They may also receive dual immunotherapy with nivolumab plus ipilimumab.

Patients with HER2-positive disease and no 

 mutations may receive either a combination of trastuzumab (Herceptin) plus pertuzumab (Perjeta).

 They may also receive lapatinib (Tykerb).

 fusion positive disease, with no evidence of 

mutations, may receive larotrectinib (Vitrakvi) or entrectinib (Rozlytrek).

Rone KA. Advances in gastrointestinal cancers: shifting evidence into practice. Presented at: 

Kawakami H, Zaanan A, Sinicrope FA. Microsatellite instability testing and its role in the management of colorectal cancer. 

. 2015;16(7):30. doi:10.1007/s11864-015-0348-2

Dienstmann R, Salazar R, Tabernero J. Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer. 

. 2018;38:231-238. doi:10.1200/EDBK_200929

Porru M, Pompili L, Caruso C, Biroccio A, Leonetti C. Targeting KRAS in metastatic colorectal cancer: current strategies and emerging opportunities. 

. 2018;37(1):57. doi:10.1186/s13046-018-0719-1

Allegra CJ, Rumble RB, Hamilton SR, et al. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015. 

. 2016;34(2):179-185. doi:10.1200/JCO.2015.63.9674

Al-Shamsi HO, Alhazzani W, Wolff RA. Extended RAS testing in metastatic colorectal cancer-Refining the predictive molecular biomarkers. 

. 2015;6(3):314-321. doi:10.3978/j.issn.2078-6891.2015.016

Gong J, Cho M, Fakih M. RAS and BRAF in metastatic colorectal cancer management. 

. 2016;7(5):687-704. doi:10.21037/jgo.2016.06.12

Larki P, Gharib E, Yaghoob Taleghani M, Khorshidi F, Nazemalhosseini-Mojarad E, Asadzadeh Aghdaei H. Coexistence of 

 mutations in colorectal cancer: a case report supporting the concept of tumoral heterogeneity. 

. 2017;19(suppl 1):113-117. doi:10.22074/cellj.2017.5123

Sandhu J, Wang C, Fakih M. Clinical response to T-DM1 in HER2-amplified, KRAS-mutated metastatic colorectal cancer. 

. 2020;18(2):116-119. doi:10.6004/jnccn.2019.7371

Emmanouilides C, Sfakiotaki G, Androulakis N, et al. Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. 

Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients With KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. 

. 2017;317(23):2392-2401. doi:10.1001/jama.2017.7105

Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. 

. 2014;15(10):1065-1075. doi:10.1016/S1470-2045(14)70330-4

Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. 

. 2008;99(3):455-458. doi:10.1038/sj.bjc.6604530

Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. 

. 2010;28(31):4706-4713. doi:10.1200/JCO.2009.27.6055

Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. 

. 2015;16(13):1306-1315. doi:10.1016/S1470-2045(15)00122-9

Van Cutsem E, Tejpar S, Vanbeckevoort D, et al. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. 

. 2012;30(23):2861-2868. doi:10.1200/JCO.2011.40.9243

Van Cutsem E. Optimizing administration of epidermal growth factor receptor-targeted agents in the treatment of colorectal cancer. 

. 2007;6(suppl 2):S60-S65. doi:10.3816/ccc.2007.s.004

Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. 

. 2015;372(26):2509-2520. doi:10.1056/NEJMoa1500596

Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. 

. 2017;18(9):1182-1191. Published correction appears in 

Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. 

. 2018;36(8):773-779. doi:10.1200/JCO.2017.76.9901

Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. 

. 2019;20(4):518-530. doi:10.1016/S1470-2045(18)30904-5

Sartore-Bianchi A, Trusolino L, Martino C, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. 

. 2016;17(6):738-746. Published correction appears in 

At the 6th Annual SONO meeting, Kelley A. Rone, DNP, RN, AGNP-C, reviewed evidence supporting molecular testing in patients with colorectal cancer. 

Molecular Profiling Is a Necessity in Colorectal Cancer Treatment 

Most patients are fit to receive a PARP inhibitor for the treatment of ovarian cancer, according to Paula Anastasia, RN, MN, AOCN; however, certain patients may need to start on a lower dose.

Anastasia, a gynecologic oncology clinical nurse specialist for UCLA Health, recently presented on 

 Anastasia discussed the circumstances in which a patient may not be fit for PARP inhibition, even if it was standard of care.

Patients who have poor performance status, for example, or other comorbidities may require an adjusted dosage. However, it is important to note that lower doses do not translate to sub therapeutic benefit.

Other important considerations include individual adverse event profiles, chemotherapy responses, and whether a patient is able to adhere to the administration guidelines, as these are oral medications.

Anastasia also illuminates the fact that, for many patients, the price of these therapies represents a major barrier to care. “These medications can be very expensive, and I’ve [seen] copays of $0 and I’ve [seen] copays of $5000 to $10,000,” she said.

According to Anastasia, ineligibility because of financial burden is not talked about in regard to PARP inhibitors, and although there are copay assistance programs, they are largely underutilized. She notes that she has been successful in obtaining grants for her patients and that leveraging pharmaceutical companies can be helpful.

“It can sometimes be time consuming, but the copay assistance programs, and access groups will do some of the legwork for us.”

Videos

Paula Anastasia, RN, MN, AOCN, highlights circumstances in which patients may not be eligible to receive benefit with a PARP inhibitor. 

Annual School of Nursing Oncology

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

Beth Sandy on Incorporating Amivantamab and Mobocertinib into Clinical Practice for Patients With EGFR Exon 20 Insertion NSCLC

Targeted Therapy Approvals Improve Outcomes, Expand Options for Patients With NSCLC

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

Rone Discusses Exciting Immunotherapy Research in Gastrointestinal Cancer

Nurse Navigators Can Help Alleviate Medical Distrust, Improve Clinical Trial Enrollment