Roundtable Roundup: Frontline Renal Cell Carcinoma Therapy

Ulka N. Vaishampayan, MBBS

Clinical Professor, Medical Oncology

Urologic Oncology Clinic

Rogel Cancer Center

University of Michigan Health

Ann Arbor, MI

David A. Braun, MD, PhD

Assistant Professor of Medicine, Medical Oncology

Louis S. Goodman and Alfred Gilman Yale Scholar

Yale Cancer Center

Yale School of Medicine

New Haven, CT

CASE SUMMARY

• A 61-year-old man, married, with 2 grown children and 5 grandchildren who live nearby and an active lifestyle (walks daily, golfs regularly)
• History of low-volume, indolent metastatic clear cell renal cell carcinoma (ccRCC)
• Underwent left nephrectomy and adrenalectomy
• Observation based on low-volume, indolent behavior of disease and patient preference
• Three years after nephrectomy: continued indolent growth on scans, increased total tumor burden, new paratracheal lymph node (2 × 1.5 cm), and more than 10 pulmonary nodules based on CT scan
• Metastatic ccRCC confirmed by lung biopsy
• Laboratory results within normal limits
• ECOG performance status: 0

VAISHAMPAYAN: The liver metastases are not part of the IMDC [International mRCC Database Consortium] risk criteria, but when we see liver metastases, it changes our thinking about the patient. The National Comprehensive Cancer Network guidelines [do not always] help because [they] still include 3 regimens as preferred, which [are] axitinib [Inlyta]/pembrolizumab [Keytruda], cabozantinib [Cabometyx]/nivolumab [Opdivo], and lenvatinib [Lenvima]/pembrolizumab.¹ Ipilimumab [Yervoy]/ nivolumab is only approved [by the] FDA in [patients with] intermediate- or poor-risk [disease]. So [it isn’t approved] in favorable-risk disease, which is what this patient has, although we did discuss that with liver metastases you would have concerns about considering this as favorable-risk disease.

But these are the 3 regimens, and single-agent cabozantinib and multiple tyrosine kinase inhibitors are options. Ipilimumab/nivolumab is [the] other recommended regimen because it was looked at in patients with favorable-risk disease. But it did not show progression-free survival and overall survival [OS] benefit, so because of that, it is not approved [by the] FDA.

BRAUN: There’s always a caution with cross-trial comparisons. [The CheckMate 214 (NCT02231749), KEYNOTE-426 (NCT02853331), CheckMate 9ER (NCT03141177), and CLEAR (NCT02811861) trials] have different patient populations, different percentages of patients [with] favorable-risk [disease]…and different durations of follow-up.^2-5

So when we look at median OS and response rate, it’s important to take [these] with a grain of salt. One of the things that I look at is the OS HR [because] they at least had a uniform comparator with sunitinib. We see that for OS, the HR is roughly equivalent across these different trials. There are a lot of similarities, probably more similarities than differences. Response rates are high across the board. [Those are] highest in the lenvatinib/pembrolizumab combination. That’s where we see the highest complete response rates, but it's a different patient population, more patients with favorable-risk disease.⁵ Then we see different primary progressive disease rates.

_REFERENCES

_{1. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 4.2023. Accessed February 14, 2023. https://bit.ly/3RbPK6X}

_{2. Motzer RJ, Tannir NM, McDermott DF, et al. 661P conditional survival and 5-year follow-up in CheckMate 214: first-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in advanced renal cell carcinoma (aRCC). Ann Oncol. 2021;32(suppl 5):S685-S687. doi:10.1016/j.annonc.2021.08.057}

_{3. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): results from 42-month follow-up of KEYNOTE-426. J Clin Oncol. 2021;39(suppl 15):4500. doi:10.1200/JCO.2021.39.15_suppl.4500}

_{4. Choueiri TK, Powles T, Burotto M, et al; CheckMate 9ER Investigators. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841. doi:10.1056/NEJMoa2026982}

_{5. 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}