Evidence continues to accumulate that hypertension and possibly neutropenia represent “clinical biomarkers” of targeted treatments’ antitumor efficacy in patients with metastatic renal cell carcinoma (mRCC), experts told Cancer Therapy Advisor.
The rationale for such clinical biomarkers of targeted agent efficacy against cancer seems straight-forward: like molecular biomarkers of tumor sensitivity or response to treatment, patients’ on-target adverse events such as hypertension might also predict drug efficacy, because of presumed shared or overlapping molecular mechanisms.
“I think it’s likely this is real,” said Assistant Professor of Urologic Sciences Peter Black, MD, FACS, of the University of British Columbia in Canada. “Especially for hypertension, I think there’s mounting evidence, mostly retrospective, for on-target hypertension showing that therapy is working.”
Hypertension is an increasingly “well-established” biomarker of on-target efficacy for sunitinib, agreed James J. Hsieh, MD, PhD, of the Human Oncology and Pathogenesis Program and Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center in New York, NY.
“We do see that association: patients who develop on-target toxicity, do better,” Dr Hsieh told Cancer Therapy Advisor. Although these are adverse events, they can be good signs because they are on-target.
Two recently-published studies supported that assessment.1,2 The larger of these (n = 770), published in the British Journal of Cancer (BJC), found that sunitinib-associated hypertension and neutropenia are prognostic clinical biomarkers of mRCC survival times.1
Hypertension and neutropenia “likely represent the underlying biology of disease, so benefits would be sustained with their appropriate management,” coauthor Brian Rini, MD, of the Cleveland Clinic Taussig Cancer Institute and Glickman Urological Institute in Cleveland, OH, told Cancer Therapy Advisor.
Dr Rini’s lab has previously established that management of hypertension does not diminish sunitinib’s anticancer efficacy, he noted.
The BJC study’s findings were consistent with findings from a smaller study (n = 181) reported in the January issue of BJU International, which found that sunitinib-induced hypertension and neutropenia—as well as thrombocytopenia—predict survival times among patients with mRCC.2
These adverse events were significantly associated with progression-free survival (PFS) among 181 patients who received sunitinib.2 Hypertension and neutropenia, but not thrombocytopenia, were also associated with overall survival (OS).2
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Patients who developed all 3 “had significantly better outcome than patients without these adverse events,” with a response rate of 47% vs 4% and a median PFS of 27 vs 3.5 months (P < 0.001 for each).2 OS data were still immature, with OS not reached among patients who developed all 3 AEs, vs a median OS of 5.3 months among those who did not (P < .001).2
“The BJC paper had a much larger cohort and it’s a very good study,” commented Dr Hsieh. “The BJUI study is smaller, so I try not to get too excited about it, with the lower patient numbers. Having said that, though, both of them look at similar parameters and come to very similar conclusions.”