New Options Emerge in Frontline, Adjuvant RCC Care

Robert S. Alter, MD

Therapeutic options for patients with renal cell carcinoma (RCC) have increased rapidly in the past decade, yet the field is still poised to expand significantly in the coming years, said Robert S. Alter, MD.

“Now, instead of hoping that a patient has a response and a slight improvement, we can use a sequence of drugs to really prolong progression-free survival (PFS) and overall survival (OS),” said Alter, co-chief of Urologic and Head and Neck Oncology at John Theurer Cancer Center. “We can not only help patients improve their PFS and OS, but can improve their quality of life, as well. We now have powerful therapies that really extend patients’ survival.”

At the 2016 ESMO Congress, findings were presented that looked promising for advancing RCC treatment. These included the phase II CABOSUN trial, which demonstrated that cabozantinib (Cabometyx) reduced the risk of progression or death by 34% compared with sunitinib (Sutent) in the frontline setting for patients with metastatic RCC.^1,2 Cabozantinib also demonstrated a median PFS 2.6 months longer than sunitinib and an overall response rate of 46% versus 18% with sunitinib.^1,2

Another study presented at ESMO, the S-TRAC trial, showed that sunitinib extended disease-free survival versus placebo as an adjuvant therapy for patients with RCC at high risk of recurrence.

OncLive: What studies are you most excited about right now in RCC?

How will these findings impact the standard first-line therapy in RCC?

In an interview with OncLive, Alter discussed both clinical trials, as well as the potential for immunotherapy in RCC in the first- and second-line settings.Alter: There has been a lot of excitement around utilizing cabozantinib as first-line therapy compared with sunitinib. They were compared in a head-to-head clinical trial that was presented at the 2016 ESMO Congress. The cabozantinib arm had a much-improved PFS; there was a 34% reduction in the time to progression or death compared with sunitinib. They had a similar percentage of adverse events. There was a slightly improved response rate, as well, with cabozantinib.The patients in the trial had intermediate- or poor-risk RCC. We will need to ask how this will impact not just poor- and intermediate-risk patients, but how do we utilize these data for good-risk patients. This will all depend on whether cabozantinib gets FDA approval in the first-line setting, obviously. If it does, what indications will it get approved for regarding the risk factors of the patients?

Giving cabozantinib as a first-line therapy may be the first paradigm-changing area, if it is indeed approved. The question then is, do we now sequence this as a TKI followed by a TKI in second-line therapy, or do we now utilize immunotherapy as second-line therapy? That question will be generated by physician experience more than it is data-driven.

Do you see an eventual role for immunotherapy in the first-line setting?

The combination of lenvatinib (Lenvima) and everolimus (Afinitor) are also being considered for first-line therapy. That study is just beginning in several centers and the data will not be out for at least 2 years.There are clinical trials utilizing single-agent or combination immunotherapy as a first-line therapy for RCC. That is going to be very exciting, as well. We definitely see data from patients on clinical trials with melanoma who respond in the first-line setting and we can look at those patients and see how they benefit from utilizing immunotherapy early.

Are there any interesting data worth highlighting outside of the frontline setting?

There are studies going on now, that hopefully will be presented in the course of the next year, which may present us with a new option for immunotherapy. Rather than utilizing a TKI for first-line therapy, we may be able to consider utilizing an immunotherapy for frontline, as well. Performance status will have to be a consideration, as will comorbidities. Sometimes, patients with certain conditions may perform better with 1 mechanism of action versus another.At ESMO, there were also phase III data presented looking at sunitinib versus placebo in the adjuvant setting for patients with locoregional RCC that are at high risk of recurrence. There was an improvement seen with sunitinib in PFS, as well as OS. This could change the paradigm as to how we treat our patients right now; there is no standard adjuvant therapy for RCC. There are 2 other adjuvant trials that have closed and are yet to be presented, so questions do still remain.

References

1. Choueiri TK, Halabi S, Sanford B, et al. Cabozantinib versus sunitinib (CABOSUN) as initial targeted therapy for patients with metastatic renal cell carcinoma (mRCC) of poor and intermediate risk groups: results from ALLIANCE A031203 trial. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA30.
2. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the alliance A031203 CABOSUN trial [published online November 14, 2016]. J Clin Oncol. doi:10.1200/JCO.2016.70.7398.