Pharmacists Play Key Role Navigating Changing Lines of Therapy for Renal Cell Carcinoma

In a Pharmacy Times Clinical Forum, Kirollos Hanna, PharmD, BCPS, BCOP, FACC, director of pharmacy at Minnesota Oncology, assistant professor of pharmacy at the Mayo Clinic College of Medicine in Rochester, Minnesota, hosted a discussion about clear cell renal cell carcinoma (ccRCC), during which panelists highlighted the unmet needs in post-first-line therapy, dynamic changes in treatment approaches, and the pivotal role of pharmacists for patient-centered care.

“It is estimated that in the [United States], just below 80,000 patients will be diagnosed with kidney cancer or cancer of the renal pelvis, and about 14,000 of these patients are estimated to succumb to disease or were estimated to succumb to disease in 2022,” Hanna said in the clinical forum.

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He added that approximately 4% of new cancers are RCC. Approximately 85% of patients have kidney tumors that are considered RCC and 70% of those are ccRCC, according to Hanna. First-line treatments can include medications, metastasectomy or stereotactic body radiation therapy, ablative techniques for oligometastatic disease, or metastasectomy with complete resection of disease, followed by adjuvant pembrolizumab within 1 year of nephrectomy and best supportive care, according to the presentation.

“Historically, [vascular endothelial growth factor (VEGF)] inhibition has played a significant role in this patient population. But in the past several years we started to see not only VEGF inhibition, but also immunotherapy [and] combinations of VEGF inhibitors with [immunotherapy]. We have combination therapies with immunotherapy together, they are [ipilimumab/nivolumab] combinations. And again, if you look at the National Comprehensive Cancer Network guidelines, they really breakdown the recommendations based on patients falling into sometimes favorable risk, intermediate, or poor risk disease,” Hanna said.

When switching from a first-line to second-line treatment, the panelists agreed that sometimes it’s difficult for patients who had difficult outcomes with their therapy to change from one treatment to another that could have similar issues. Panelist Cassia Griswold, PharmD, BCOP, clinical pharmacy specialist at Mayo Clinic in Phoenix, Arizona, added that the second line becomes more challenging to navigate compared to first line treatments.

“It's definitely a lot more challenging to navigate. A lot of the trials that were done in the second- or third-line setting were really only after the first generation [tyrosine kinase inhibitors (TKIs)] that are not really part of standard practice,” Griswold.

Candy Peskey, PharmD, BCPS, BCOP, a cancer center care team pharmacist with Mayo Clinic in Rochester, Minnesota, echoed Griswold, adding that providers at her institution typically go with cabozantinib in the second line setting as a single agent because the first-line agent is usually an immunotherapy or a therapy without a TKI. She said most current data in the guidelines for the second line were studied against sunitinib or pazopanib, which are not used in the first line.

Justin Julius, PharmD, BCOP, DPLA, manager of Oncology Clinical Pharmacy Services at Allegheny Health Network Cancer Institute in Pittsburgh, Pennsylvania, added that about 80% of his institution’s patients progress from first- to second-line therapies, and then there is a very steep decline of who goes onto a third line therapy. He also said that most patients whose cancer is treated with cabozantinib often do poorly and don’t want to move onto the third line.

According to the presentation, the median progression free survival with tivozanib in clinical trials was 5.6 months, compared to 3.9 with sorafenib. The objective response rates were 71% and 46%, respectively. Further, the overall survival was 16.4 months compared to 19.7 months, respectively, and the duration of response was not reached for tivozanib.

Notably, Hanna said the TIVO-3 trial of tivozanib and sorafenib found that hypertension, a common tolerability concern, was higher in the sorafenib group, as was the degree of palmar-plantar erythrodysesthesia.

To combat toxicities, Chelsea Gustafson, PharmD, BCOP, clinical pharmacy specialist with Community Health Network at MD Anderson Cancer Center in Kokomo, Indiana, said, “I do all the initial educations on any oral oncolytic [for] RCC and others that are coming through the clinic. So, all those patients receive education from a pharmacist and then, at that visit, I dictate what their follow-up schedule is going to be.”

The patient will also be seen 1 to 2 weeks later to be evaluated for any toxicities. Gustafson added that her institution’s team of clinical pharmacists is responsible “for creation of treatment plans that contain supportive medications as well as recommended labs and intervals of monitoring,” indicating the value of the pharmacists in care.

Otto added that in her clinic, a PhD student is using a toxicity monitoring mobile app for her thesis, which she is using to send daily reminders to patients for symptom tracking. Otto said the student is trying to protocolize it so that when a severe symptom is recorded, it prompts them to call their provider.

Besides adverse reactions, another large barrier to cancer medications for the patient population included access to care and affordability, Otto. Astrid Slaughter, PharmD, PhD, BCSP, BCOP, pharmacy area manager with Texas Oncology in Round Rock, Texas, added that their institution includes financial counseling for the intravenous space and a dedicated team working on either prior authorizations or securing financial assistance.

Slaughter also said sometimes they have to send oral prescriptions to external pharmacies, such as specialty or mail order pharmacies. She added that they try to send it to a pharmacy close to their home so they can pick it up, but in rural areas, it’s not always feasible.

Regardless of treatment strategies, all of the panelists agreed that including pharmacists in the care teams is essential to optimal outcomes. In addition to educating providers and patients about the regimens, pharmacists are vital to managing challenging adverse effects such as hypertension, gastrointestinal disturbances, and pain management.