First-line Therapy for Renal Cell Carcinoma

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The COMPARZ phase III noninferiority trial evaluated sunitinib versus pazopanib as first-line therapy in 1110 patients with metastatic clear cell renal cell carcinoma (RCC). Results show that progression-free survival (PFS) and overall survival (OS) outcomes of patients on pazopanib were noninferior to those on sunitinib. Brian Rini, MD, comments that there are many aspects of the study design clinicians could analyze, such as the statistics of the intent-to-treat analysis versus a per protocol analysis. Moreover, the predefined noninferiority margin was 1.25. Rini says that both pazopanib and sunitinib are effective agents, and to him, either one is a reasonable choice.

Janice Dutcher, MD, agrees that from a practical perspective, it is more relevant to choose an effective agent and become comfortable with it. Clinicians should familiarize themselves with side effect profiles and how to effectively modify doses. Dutcher comments that when these drugs first became commercially available (outside of clinical trials and the centers that had experience with them), patients were discontinuing the medication within a month. The median time patients were maintained on sunitinib in the first clinical trial was 8 months, so the challenge to clinicians became how to manage side effects so that individuals could continue their therapy.

An open label phase II trial, RECORDS-3, evaluated first-line treatment with sunitinib followed by the mTOR inhibitor everolimus compared with the opposite sequence, everolimus followed by sunitinib, notes Daniel Heng, MD. Participants were initiated on either sunitinib or everolimus. Once there was evidence of progression, participants were crossed over to the other agent. The study suggested that patients have better outcomes using sunitinib compared with everolimus as first-line therapy. According to Heng, these results reinforced oncologists’ current practice of administering a TKI first-line in good-risk and intermediate-risk patients and switching to an mTOR inhibitor after a failed response.

SWITCH, a phase III superiority trial, was a sequential study that examined patients receiving sorafenib followed by sunitinib versus those receiving sunitinib followed by sorafenib. The study found that PFS and OS were statistically similar in both groups. Dutcher advises clinicians to administer these agents in a sequence based on their level of comfort.