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Choueiri Reflects on Recent RCC Advances

Angelica Welch
Published: Thursday, Jul 26, 2018

Toni K. Choueiri, MD
Toni K. Choueiri, MD
The 2018 ASCO Annual Meeting included a number of clinical highlights in renal cell carcinoma (RCC), according to Toni K. Choueiri, MD. On the heels of multiple FDA approvals throughout the latter half of 2017 and the beginning of 2018, the field continues to rapidly shift.

“RCC today, as well as for the past few years—and certainly for the next 2 to 5 years—is going to be one of the most dynamic fields in solid tumor oncology,” said Choueiri. “I am very glad, blessed, and humbled to be in this field.”

The CARMENA trial (NCT00930033) in patients with synchronous metastatic RCC demonstrated the noninferiority of sunitinib (Sutent) to cytoreductive nephrectomy plus sunitinib, the current standard of care. Phase III findings showed a median overall survival (OS) of 18.4 months for sunitinib compared with 13.9 months for the standard arm (HR, 0.89; 95% CI, 0.71-1.10).

Additionally, sunitinib showed a similar median OS in patients with intermediate (23.4 vs 19.0 months; HR, 0.92; 95% CI, 0.68-1.24) and poor prognosis (13.3 vs 10.2 months; HR, 0.85; 95% CI, 0.62-1.17). Choueiri noted that questions remain, but these results will be referenced and studied for years to come.

Additional studies in RCC are ongoing and of interest. For example, the randomized, double-blind, placebo-controlled, phase II CANTATA study is evaluating CB-839, an oral glutaminase inhibitor, with cabozantinib (Cabometyx) versus cabozantinib with placebo in patients with metastatic RCC (NCT03428217). Cabozantinib was approved by the FDA in December 2017 for previously untreated patients with advanced RCC.

Studies with pembrolizumab (Keytruda), atezolizumab (Tecentriq) plus bevacizumab (Avastin), and sorafenib (Nexavar), are also shaking up the landscape, Choueiri noted.

With all of these advances—and more on the way—optimal sequencing remains a challenge. However, Choueiri said that there may be a future where multiple sequences are plausible.

In an interview with OncLive, Choueiri, director of the Kidney Cancer Center at Dana-Farber Cancer Institute, recapped some of the most significant data presented thus far in 2018 for the treatment of patients with RCC.

OncLive: Can you reflect on the CARMENA trial that was presented at the 2018 ASCO Annual Meeting?

Choueiri: It was a big conference for kidney cancer; we had a presentation that made it to the plenary session, [which was] CARMENA. This study asked the question of VEGF-targeted therapy in the modern setting, namely sunitinib, and whether taking the kidney out in metastatic RCC by cytoreductive nephrectomy makes sense. What was presented in the past in the cytokine era, as well as the many retrospective studies, was that cytoreductive nephrectomy helps.

Here in the CARMENA study, there was no difference in OS in the sunitinib monotherapy patients versus those who had sunitinib and then underwent a cytoreductive nephrectomy. This is likely paradigm shifting. Overall, many other clinical endpoints were looked at, such as progression-free survival (PFS), which did not show a difference. The paper was published at the same time as the article in the New England Journal of Medicine. 

We will still look at CARMENA in great detail for the months and years to come. Again, patients with poor-risk RCC should not even be considered. The question is, “Should we consider cytoreductive nephrectomy at baseline or later on in patients with a large primary tumor with great performance status and very limited disease burden outside the kidney?” That is an open question and an important study. 

What other oral presentations took place at this year’s meeting?

One was a study of pembrolizumab (Keytruda), another was a study of the combination of atezolizumab and bevacizumab, and then there was a study of sorafenib. They all happen to be in untreated advanced clear cell RCC.

Pembrolizumab was tested and showed a response rate of 38% in this untreated population. There were usual single-agent immune-related adverse events. In PD-L1–positive patients, the response rate was 50%, which begs the question, “Can this agent be used alone or should we use it in combination?” We do not have a lot of data in this context with single-agent PD-1/PD-L1 inhibitors. We do have data with pembrolizumab and atezolizumab and very little data with nivolumab (Opdivo). The story is evolving, and pembrolizumab is being tested in first-line therapy with axitinib (Inlyta) in combination as well as in the adjuvant setting.




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