Sunitinib Toxicities May Predict Better mRCC Patient Survival
On-treatment neutropenia and hypertension are independently associated with decreased mortality risk.
Neutropenia and hypertension that develop while on sunitinib therapy for metastatic renal cell carcinoma (mRCC) are independently associated with improved survival, according to researchers.
Incorporating these adverse events (AEs) into the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model leads to improved prognostic accuracy.
In a paper published online in the British Journal of Cancer, Frede Donskov, MD, of Aarhus University Hospital in Denmark, and colleagues concluded that ‘identification of neutropenia and hypertension and, to a lesser degree, hand-foot syndrome, during sunitinib therapy may enable physicians to predict which patients are most likely to benefit from therapy.”
In addition, lack of neutropenia or hypertension within 12 weeks could be incorporated as a stratification factor in prospective studies assessing whether dose adjustment or switching to an alternative treatment strategy may change clinical outcome. “In the meantime, providers who observe these AEs in their patients should be encouraged to continue sunitinib therapy, while managing AEs with standard medical treatment, with or without dosing interruption and/or dose reduction, as clinically indicated.”
In a retrospective study of 770 sunitinib-treated mRCC patients identified using a pooled database of 5 prospective sunitinib trials, Dr. Donskov's team found that on-treatment neutropenia and hypertension were associated with longer progression-free survival (PFS) and overall survival (OS) independent of baseline prognostic factors, including IMDC criteria. At 12 weeks, development of neutropenia was associated with a significant 28% decreased risk of disease progression and 29% decreased risk of death. Hypertension and hand-foot syndrome were associated with a significant 32% and 36% decreased risk of death, respectively.
Using the IMDC prognostic model, median OS was 37.9, 19.9, and 8.0 months in the favorable-, intermediate-, and poor-risk groups, respectively. Adding neutropenia and hypertension to the model resulted in significantly improved prognoses. In all risk groups, patients who developed both neutropenia and hypertension had significantly longer median OS compared with patients who developed neither AE (favorable risk, 45.3 vs. 19.5 months; intermediate risk, 32.5 vs. 8.0 months; and poor risk, 21.1 vs. 4.8 months).
The new study adds to existing evidence that sunitinib-induced AEs predict a good prognosis in mRCC patients. Last year, Juhana Rautiola, MD, of Helsinki University Central Hospital in Finland, and colleagues reported in BJU International (online ahead of print) that neutropenia, hypertension, and thrombocytopenia were associated with significant improvements in PFS and OS based on a study of 181 mRCC patients treated with sunitinib. The presence of all 3 AEs was associated with significantly longer PFS and OS compared with the absence of all 3 AEs (27.1 vs. 3.5 months and OS not reached vs. 5.3 months, respectively).
Daniel M. Geynisman, MD, a genitourinary medical oncologist at Fox Chase Cancer Center in Philadelphia, praised the new study. “Dr. Donskov and colleagues are to be commended for tackling an important and practical question: how to predict response and outcomes to standard VEGF therapy in renal cell carcinoma, during rather than prior to treatment, based on easily accessible clinical patient variables,” Dr. Geynisman told Renal & Urology News. “The study was able to extend previous prognostic factors even further, by incorporating the presence or absence of on-treatment hypertension, neutropenia, and hand-foot syndrome, to more accurately stratify patients and adjust prognosis depending on how they respond.”
These biomarkers are readily available in the clinic, as they require no special tests and can help the clinician more accurately guide discussions with patients about expectations and future treatment options, said Dr. Geynisman, assistant professor of medical oncology at Temple University School of Medicine in Philadelphia.
“Given the expanding armamentarium of therapies in metastatic renal cell carcinoma, refining our ability to predict responders and non-responders to VEGF therapy is critical so as to appropriately guide patients to potentially most effective therapies and clinical trials for them; findings from this study may help us do just that.”