Claud Grigg, MD, medical oncologist, Levine Cancer Institute, Atrium Health, discusses the design and results of the CABOSUN trial looking at the frontline treatment of patients with metastatic renal cell carcinoma (mRCC).

CABOSUN was a randomized phase II trial looking at the use of cabozantinib (Cabometyx), which is dosed daily, versus that of sunitinib (Sutent), which is dosed on a 4-week-on, 2-week-off schedule. This was a relatively small study, Grigg says, which enrolled only about 150 patients. CABOSUN was designed to detect an improvement of progression-free survival (PFS) with cabozantinib over the long-time standard of care sunitinib. This was a positive study, as data showed a median PFS of 8.6 months with the newer-generation TKI versus 5.3 months with sunitinib.

Despite meeting its primary endpoint, the study is criticized for its low PFS, Grigg notes. Overall response rate was also considerably modest at 20% and 9% with cabozantinib and sunitinib, respectively. However, Grigg concludes that it is still reassuring to have an additional frontline option for these patients. Recent data has suggested the efficacy of checkpoint inhibitors in the frontline setting, so ongoing research is being geared toward determining the feasibility of combining TKIs with anti-PD—1 and CTLA-4 agents.

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Claud Grigg, MD, medical oncologist, Levine Cancer Institute, Atrium Health, discusses the design and results of the CABOSUN trial in metastatic renal cell carcinoma.

Dr. Grigg Discusses CABOSUN Trial in mRCC

Claud Grigg, MD, medical oncologist, Levine Cancer Institute, discusses the future treatment landscape of renal cell carcinoma (RCC).

In the next 1 to 2 years, Grigg predicts that physicians will see various combinations of immunotherapies and tyrosine kinase inhibitors (TKIs) in the frontline setting. The concern, explains Grigg, is what the second-line setting will have to offer. Physicians know that cabozantinib (Cabometyx) has activity in patients who have previously progressed on other TKIs, so combinations are likely to carry into the second-line setting, adds Grigg. Cabozantinib is approved as both a frontline therapy for patients with advanced RCC and a second-line therapy for patients with metastatic disease.

Novel immunotherapy may have a role in later lines of therapy. In April 2018, the FDA approved the frontline combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of patients with poor- and intermediate-risk advanced RCC. In addition to existing therapies, Grigg hopes to see the development of newer agents in the next 5 years.

Dr. Grigg on the Future Treatment Landscape of Renal Cell Carcinoma

Claud Grigg, MD, medical oncologist, Levine Cancer Institute, discusses frontline tyrosine kinase inhibitors (TKIs) in renal cell carcinoma (RCC).

TKIs are often referred to as inhibitors of the VEGF receptor pathway, but in reality, inhibit other kinases in the cell, says Grigg. For example, sunitinib (Sutent) is a potent inhibitor of KIT and FLT3. Additionally, cabozantinib (Cabometyx) inhibits MET and AXL in addition to other kinases. It is important to consider the toxicity profiles of these agents when deciding which one to administer, adds Grigg. The CABOSUN data revealed that the toxicities for sunitinib are mainly hematologic, whereas higher rates of stomatitis and fatigue were observed in the cabozantinib arm.

Physicians also have to consider whether patients need a quick response or not. The IMDC risk criteria are often used in that regard, notes Grigg. However, physicians looking for higher response rates and longer progression-free survival should turn to cabozantinib in the first-line setting, concludes Grigg.

Claud Grigg, MD

Articles

Dr. Grigg Discusses CABOSUN Trial in mRCC

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Dr. Grigg on Frontline Tyrosine Kinase Inhibitors in RCC