Pazopanib in Patients with Treatment-Naïve or Cytokine-Pretreated Advanced RCC
Slides from the ASCO presentations and transcribed comments from a related "Think Tank" (June 10, 2009) featuring
Thomas E Hutson, DO, PharmD, Robert J Motzer, MD and David I Quinn, MBBS, PhD
Presentations discussed in this issue:
Sternberg CN et al. A randomized, double-blind phase III study of pazopanib in treatment-naïve and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). ASCO 2009;Abstract 5021.
Hawkins RE et al. An open-label extension study to evaluate safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). ASCO 2009;Abstract 5110.
NEIL LOVE, MD: Tom, we've been talking about dose intensity with VEGF tyrosine kinase inhibitors, particularly sunitinib, and a related issue is whether other less toxic agents can be identified that might allow for longer-term treatment and maybe greater efficacy. What's your take on this ASCO paper on pazopanib, and what are your global thoughts at this point on side effects, particularly compared to sunitinib?
THOMAS E HUTSON, DO, PHARMD: Clinical trial data such as this report suggest that the long-term toxicities that make the use of sunitinib difficult for patients — fatigue, diarrhea, mucositis, hand-foot syndrome — appear to be significantly less with pazopanib. My general anecdotal experience also is that pazopanib may be more tolerable than sunitinib with long-term use. The side-effect profile is certainly different with pazopanib in that you see some liver transaminase elevations and also hypertension and skin hypopigmentation. I treated an African-American patient who developed vitiligo-like areas on the face with the medication.
DR LOVE: What about efficacy compared to sunitinib?
DR HUTSON: Clearly, definitive data will come out of the randomized trial evaluating both, but based on what we know today, one would say that pazopanib is in the same ballpark of efficacy as sunitinib, based on progression-free survival and response rate.
DR LOVE: Bob, what's your take on this?
ROBERT J MOTZER, MD: We really need the Phase III comparison, but pazopanib is a highly active compound, as seen in this ASCO report. The one toxicity that needs to be addressed is the hepatic toxicity, but otherwise, the frequencies of other toxicities that have been problematic with sunitinib, including fatigue and hand-foot syndrome, were reported with less frequency.
DAVID I QUINN, MBBS, PHD: Based on this study and other data, I think pazopanib will be a viable alternative for patients in the first-line metastatic setting and also with disease progression after a cytokine. Our view is that pazopanib is probably better tolerated than sunitinib in terms of fatigue, but I want to see Phase III data to validate that. We may see a little more hypertension than with sunitinib, which is a bit of an issue to manage in some patients. But, I think it's a player in the arena. When we look at the current options for advanced renal cell carcinoma, it's immunotherapy/cytokines, VEGF inhibition and mTOR inhibition — it's a matter of how to optimally deliver these. I think having another agent available is a good thing because there's more choice.
Dr Hutson is Director of the GU Oncology Program at Texas Oncology-Baylor Charles A Sammons Cancer Center and Co-Chair of US Oncology GU Research in Dallas, Texas.
Dr Motzer is Genitourinary Medical Oncologist in New York, New York.
Dr Quinn is Medical Director of Norris Cancer Hospital and Clinics, Leader of Developmental Therapeutics and Head of the GU Cancer Section in the Division of Cancer Medicine and Blood Diseases at USC/Norris Comprehensive Cancer Center in Los Angeles, California.