Eric Jonasch, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the use of single-agent pembrolizumab (Keytruda) in the treatment of patients with metastatic non—clear cell renal cell carcinoma (RCC).

Among recent notable trials in the metastatic RCC space is the KEYNOTE-427 study, which looked at pembrolizumab monotherapy in patients with non—clear cell histology. Jonasch says this patient population is a complex one with a number of different molecular entities that warrant individualized approaches rather than one homogenous approach.

In the study, objective response rate (ORR) was 24.8% with the PD-1 inhibitor, which Jonasch says is one of the highest ORRs seen in this patient population. Moreover, it appeared that pembrolizumab was more effective in patients with papillary RCC, and less potent in patients with chromophobe histology.

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Eric Jonasch, MD, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses the use of single-agent pembrolizumab in the treatment of patients with metastatic non–clear cell renal cell carcinoma.

Dr. Jonasch on Single-Agent Pembrolizumab in Non-Clear Cell RCC

Eric Jonasch, MD, professor, The University of Texas MD Anderson Cancer Center, discusses sequencing challenges facing patients with renal cell carcinoma (RCC).

A sequencing challenge in the second-line setting is whether to start with a checkpoint antibody, such as nivolumab (Opdivo) or a multikianse inhibitor like cabozantinib (Cabometyx).

Nivolumab is well tolerated for the majority of patients who receive it. There is a subset of individuals who benefit from it. At this point in time, there are not good predictors of which agent should be given to which patient.

Dr. Jonasch on Sequencing Challenges in RCC

Eric Jonasch, MD, professor, The University of Texas MD Anderson Cancer Center, discusses the CABOSUN study in renal cell carcinoma (RCC).

The CABOSUN study randomized more than 150 patients between sunitinib (Sutent) and cabozantinib (Cabometyx). These individuals had intermediate- and poor-risk features. The progression-free survival (PFS) for cabozantinib was clearly superior to that of sunitinib, states Jonasch.

According to Jonasch, a number of individuals who were on sunitinib came off very early in the study, which may have skewed the curves somewhat in favor of cabozantinib.

Dr. Jonasch on the CABOSUN Trial in RCC

Eric Jonasch, MD, professor, The University of Texas MD Anderson Cancer Center, discusses the potential of immunotherapy for patients with sarcomatoid renal cell carcinoma (RCC).

Sarcomatoid RCC is a difficult area to treat from an efficacy standpoint, explains Jonasch. Emerging data suggest that immuno-oncology agents might be useful for this patient population.

There are published data demonstrating that PD-L1 expression is higher with sarcomatoid RCC and raises the hypothesis that targeting PD-1/PD-L1 might be beneficial, states Jonasch.

Dr. Jonasch on the Potential of Immunotherapy for Sarcomatoid RCC

Eric Jonasch, MD, professor, The University of Texas MD Anderson Cancer Center, discusses the phase II study of alternative sunitinib (Sutent) scheduling in patients with metastatic renal cell carcinoma (mRCC).

This study was testing the hypothesis that changing the schedule of sunitinib would allow patients to have lower toxicity rates and improve time on treatment and efficacy, states Jonasch. The primary endpoint was decreased grade 3 toxicity, which was not met during this study.

The patients who stayed on the study for a long period of time experienced a progression-free survival of 19 months and a response rate of 55%.

Dr. Jonasch on Alternative Sunitinib Scheduling for mRCC

Eric Jonasch, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the advancements in the first- and second-line settings for treating patients with renal cell carcinoma (RCC). Jonasch shared this insight during the 2017 

 State of the Science Summit on Genitourinary Cancers.

There have been a handful of FDA approvals in this field over the last couple of years, Jonasch explains, which have had made decisions for physicians on which agents to use and in what sequence a bit more interesting.

For example, recent data on the frontline use of cabozantinib (Cabometyx) has shown that the agent could have eventual promise in this setting, even if it is not yet ready for primetime, he adds. In the second-line setting, there is a "richness of choice" with the available agents, including cabozantinib, nivolumab (Opdivo), and lenvatinib (Lenvima) plus everolimus (Afinitor), which all have their own mechanistic properties and side effect profiles. Each therapy may also be more valuable for one patient than another depending on their individual comorbidities.

This is proving to be an exciting era for patients with RCC, Jonasch says.

Eric Jonasch, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the advancements in the first- and second-line settings for treating patients with renal cell carcinoma (RCC). Jonasch shared this insight during the 2017 OncLive® State of the Science Summit on Genitourinary Cancers.

Dr. Jonasch on First- and Second-line Options for Patients With RCC

Eric Jonasch, MD, professor, The University of Texas MD Anderson Cancer Center, discusses the promise of immuno-oncology agents in sarcomatoid renal cell carinoma (RCC).

Sarcomatoid RCC is a difficult disease in regard to efficacy, says Jonasch. But, with studies stating that PD-L1 expression in RCC is high, the use of checkpoint antibodies could be promising.

Jonasch says that this high expression of PD-L1 supports the hypothesis that, if targeted, checkpoint antibodies could be succesful in treatment of patients with the disease.

Eric Jonasch, MD

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