Roundtable Roundup: Motzer and Ornstein Survey Participants on Frontline RCC Therapy

CASE SUMMARY

A Black woman aged 59 years with a left renal mass underwent left radical nephrectomy in December 2019 and received a diagnosis of clear cell RCC. Nine months later, she developed metastatic disease to bilateral lungs, mediastinum (35 × 38 mm), and retroperitoneal lymph nodes. A lung biopsy confirmed stage IV RCC, clear cell histology, with Karnofsky performance status of 90%. Her hemoglobin was 11.1 g/dL, but corrected calcium, neutrophils, and platelet levels were within normal limits.

Moshe Ornstein, MD, MA

Genitourinary Medical Oncologist

Cleveland Clinic Taussig Cancer Institute

Cleveland, OH

ORNSTEIN: Probably 10% to 15% of patients in my practice with metastatic RCC are on surveillance. The first question that I ask when I see a patient with metastatic RCC is whether I need to treat that patient now or is there some role for active surveillance where I can just watch that patient. Now, if this patient had her nephrectomy 3 years ago and presented with a 0.5-cm mediastinal node and tiny lung nodules that were slowly growing, that would be one thing, but the fact that she presented within a year and had what look like fairly bulky nodes, as well as nodules in both lungs, would scare me from doing surveillance, and I would be more inclined to treat this patient.

Usually, for patients who have intermediate and poor International Metastatic RCC Database Consortium risk, I'm less inclined to do surveillance. And this patient, because the metastatic disease is within a year, or time to treatment is less than 12 months, and she has a low hemoglobin, she would fall into an intermediate-risk category. Therefore, the decision was made to initiate systemic therapy [Polls].

All the combination regimens were selected [in the poll], most selected were nivolumab [Opdivo]/ ipilimumab [Yervoy] and lenvatinib [Lenvima]/ pembrolizumab [Keytruda], and 1 vote each for axitinib [Inlyta]/pembrolizumab and cabozantinib [Cabometyx]/nivolumab.

POLLING QUESTION

A decision was made to initiate systemic therapy. What frontline therapy are you most likely to choose for this patient?

CASE UPDATE

This patient was scheduled to begin pembrolizumab at 200 mg every 3 weeks plus lenvatinib at 20 mg daily.

ORNSTEIN: All the immunotherapy/tyrosine kinase inhibitor regimens have different strategies. The difference in dosing strategies might be somewhat implicated in why the response rates, survival, and clinical outcomes were different.

I do want to highlight that, at least for this regimen, the starting dose in the phase 3 CLEAR trial [NCT02811861] was 20 mg with a first reduction of 14 mg.¹ At this point we've been giving TKIs [tyrosine kinase inhibitors] in kidney cancer for 15 years or so, and I think we have a reasonable handle for patients who are on these TKIs, and what the strategies are to mitigate the toxicity. So whether it's hand-foot syndrome, diarrhea, fatigue—when it comes to the TKI, withholding for a few days and then resuming at the same dose, dose reducing in patients who absolutely cannot tolerate a specific dose, discontinuing, etc for patients who you've done the withholding—you've done the reducing and it's challenging to keep them on lenvatinib.

Much like cabozantinib and axitinib, lenvatinib pills come in various forms. Lenvatinib comes in 10-mg and 4-mg doses, so one of the challenges that we see in clinic sometimes is patients are started, let’s say at 20 mg, and then when we dose reduce, they have all these 10-mg tablets, and they’re looking for the 4-mg tablets. It’s important to note that similar to other companies, the company that makes lenvatinib has a lenvatinib dose exchange program…where they will swap out up to approximately 2 weeks of doses of different pill size for a lower pill dosage. [That is something to] keep…in mind for your patients on this particular regimen.

_REFERENCE

_{1. Motzer R, Alekseev B, Rha SY, et al; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716}