The CLEAR Trial: Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma - Episode 1

Novel Combinations as Frontline Therapy for mRCC

An overview of current novel-based approaches for metastatic renal cell carcinoma and current treatment gaps.

Chung-Han Lee, MD, PhD: Welcome to this Targeted OncologyInvestigator Perspectives program. I’m Dr Chung-Han Lee from Memorial Sloan Kettering Cancer Center [in New York, New York]. Here I have with me Kiran. Do you want to introduce yourself?

Kiran Kehoe, RN, BSN, CCRN: Thank you. My name is Kiran Kehoe, I’m an office practice nurse, and I’ve been working alongside Dr Lee managing patients with renal cell carcinoma at Memorial Sloan Kettering Cancer Center.

Chung-Han Lee, MD, PhD: For the treatment of metastatic clear cell kidney cancer, there are multiple first-line therapy options available. However, with these multiple first-line therapies available, most build upon a PD-1 inhibitor background. There are 2 broad approaches commonly used. The first is to use combination immunotherapy with a combination of an anti-CTLA4 agent plus PD-1, such as the combination of ipilimumab plus nivolumab. The other commonly used approach is combination therapy with a PD-1 inhibitor plus a tyrosine kinase inhibitor. There are 4 tyrosine kinase inhibitor [TKI]–PD-1 inhibitor combinations that are FDA approved. These include the combinations of lenvatinib plus pembrolizumab, axitinib plus pembrolizumab, axitinib plus avelumab, and cabozantinib plus nivolumab.

There are multiple challenges that we face when we think about treatment in the first-line setting. The first is that with 2 broad categories of treatment approaches, trying to stratify patients between the 2 approaches is done completely clinically. That means we have no biomarkers that allow us to stratify patients to either approach. There are also no head-to-head trials that have compared these 2 approaches with each other. There’s no guidance across large categories of patients on whether either approach is preferable. Going down deeper when we talk about the different TKI–I/O [immuno-oncology] combinations, there remains a lot of difficulty with cross-trial comparisons to determine the optimal regimen based on the available data. All these studies have been compared with sunitinib as the comparator arm.

Furthermore, thinking forward and due to the duration of follow up for these scans, we still don’t yet know what the long-term effects of each of these regimens are. Certainly, for the combination such as ipilimumab plus nivolumab, we do have long term follow-up data. However, the approval of the TKI–I/O combinations are rather new, so the follow-up is considerably shorter compared with other regimens. Therefore, even if there are very high response rates associated with this, we’re still unsure whether those high response rates lead to durable responses for the patients.

Transcript edited for clarity.