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Novel Combinations Advance Through RCC Pipeline

Caroline Seymour
Published: Thursday, Jul 19, 2018

Peter van Veldhuizen, MD

Peter Van Veldhuizen, MD

Combination immunotherapy approaches have emerged as a key strategy in the frontline paradigm for renal cell carcinoma (RCC). Not only have these combinations improved overall responses, but they have subtly “redefined frontline alternatives,” said Peter J. Van Veldhuizen, MD, a hematologist/oncologist at Sarah Cannon Research Institute.

For example, the results of the phase III CheckMate-214 trial examined the frontline combination of nivolumab (Opdivo) and ipilimumab (Yervoy) compared with sunitinib (Sutent) and showed a 37% reduction in the risk of death in intermediate- and poor-risk patients (HR, 0.63; P <.0001).1 In April 2018, the FDA approved the combination for this patient population.

The landscape could add another immunotherapy-based regimen, following the positive results of the phase III IMmotion151 trial. In this study, the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) reduced disease progression or death by 26% for patients with previously untreated PD-L1–positive metastatic RCC. Median PFS was 11.2 months with the combination versus 7.7 months with single-agent sunitinib (HR, 0.74; 95% CI, 0.57-0.96; P = .0217).2

Beyond immunotherapy, the FDA approved cabozantinib (Cabometyx) in December 2017 for previously untreated patients with advanced RCC, based on a meaningful improvement in progression-free survival versus sunitinib (Sutent) in the phase II CABOSUN trial.

In an interview during the 2018 OncLive® State of the Science SummitTM on A Summer of Progress: Updates from ASCO 2018, Peter J. Van Veldhuizen, hematologist/oncologist, Sarah Cannon Research Institute, discussed available and emerging therapies for patients with kidney cancer.

OncLive: What are the most recent advances in the treatment of patients with kidney cancer?

Van Veldhuizen: We looked at some key trials like the CABOSUN trial, which looked at first-line cabozantinib versus sunitinib for intermediate- and high-risk patients. CheckMate-214 compared frontline nivolumab and ipilimumab with sunitinib. Both of those trials showed improved survival in the study arm compared with sunitinib. These trials have somewhat redefined frontline alternatives.

We also reviewed some of the newer combinations, such as atezolizumab and bevacizumab, which showed encouraging results. That combination is another potential frontline treatment, though it is not yet FDA approved.

In addition, we discussed the CARMENA trial, which looked at debulking nephrectomy in the metastatic setting in patients who received sunitinib alone versus debulking nephrectomy followed by sunitinib. [Debulking nephrectomy followed by sunitinib] did not show a survival advantage with sunitinib alone. There is still some question about the benefit [of nephrectomy] for selected patients.

What factors do you consider in deciding between the available frontline treatments?

The combination of nivolumab and ipilimumab is exciting because it resulted in some complete responses. The tolerability may be in question for certain patients. Performance status, age, and PD-1 status also play a role in whether or not you select that regimen.

An exploratory analysis suggests that patients with PD-1 positivity in the intermediate- and high-risk disease categories are the ones who are the most likely to benefit [from immunotherapy]. Attaining PD-L1 status may help sort out whether you choose that regimen versus a tyrosine kinase inhibitor like cabozantinib or pazopanib (Votrient) in good-risk patients.

What was the background of the IMmotion151 trial with atezolizumab and bevacizumab?

The combination is based on bevacizumab’s potential synergy with immunotherapy. It may help enhance the immune response. Even though those drugs are administered intravenously, they are generally well tolerated. There is good rationale for the combination.


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