Hypertension potential efficacy biomarker for metastatic renal cell carcinoma

Rini BI. J Natl Cancer Inst. 2011;doi:10.1093/jnci/djr128.

Issue: June 10, 2011

Patients who developed sunitinib-associated hypertension while being treated for metastatic renal cell carcinoma lived more than 30 months longer than patients with normal blood pressure, according to the results of a recently published study.

Researchers said high BP may act as a significant independent predictor of improved outcomes for patients with metastatic renal cell carcinoma, and physicians may be able to monitor BP to measure the efficacy of sunitinib (Sutent, CPPI CV) for treating advanced kidney cancer.

Researchers reviewed data collected on 4,746 patients treated with sunitinib in four separate trials, and 544 patients were evaluable for efficacy. Of those, 442 patients developed hypertension, defined by post-baseline maximum systolic BP of at least 140 mm Hg or a maximum diastolic BP of at least 90 mm Hg

Four-fifths of patients had systolic-defined hypertension and 67% had diastolic-defined hypertension.

The objective response rate was 54.8% for patients with systolic-defined hypertension compared with 8.7% for those with lower BP. The median PFS was 12.5 months (95% CI, 10.9-13.7) and median OS was 30.9 months (95% CI, 27.9-33.7) for patients with systolic-defined hypertension. The median PFS was 2.5 months (95% CI, 2.3-3.8) and median OS was 7.2 months (95% CI, 5.6-10.7) for those with lower BP.

Researchers observed similar outcomes with diastolic-defined hypertension.

Sunitinib frequently causes hypertension. Until now, there has been a general sense that hypertension was a side effect and complication of therapy. Providers have been taught to be aggressive about treating hypertension in order to prevent cardiovascular complications from sunitinib such as congestive heart failure, stroke, and myocardial infarction, but we haven’t been thinking of induced hypertension as a marker for the efficacy of this drug. Much like erlotinib-induced skin toxicity correlating with efficacy in lung cancer, this study demonstrates that many treatment outcomes are improved in patients with clear cell renal cell cancer if hypertension is induced by sunitinib — OS is longer, PFS is longer, tumor shrinkage rates are higher. And the good news is that this is these benefits persist even when the hypertension is treated with anti-hypertensives, meaning that providers can use this as a prognostic marker of efficacy of this drug after patients have been treated for 1-2 cycles. That’s a positive development because we do not see an increased risk for heart attack or stroke, and any good news for these patients can be a motivator for sticking with these agents long term. I would not recommend increasing dosage specifically to induce hypertension, especially past the FDA approved dose or outside of a clinical trial, in the absence of more clinical trial data. Hypertension can have associated significant toxicities, and sunitinib at doses higher than what is FDA approved does result in other toxicities such as hand-foot syndrome, fatigue and diarrhea that are unrelated to high blood pressure.

– Andrew Armstrong, MD ScM
Assistant professor of medicine and surgery,
Duke Comprehensive Cancer Center

Disclosure: Dr. Armstrong has received speaking fees and research support from Pfizer.

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