SAN FRANCISCO—Use of antihypertensive angiotensin system inhibitors (ASIs) such as lisinopril, captopril, and losartan significantly improved median overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) compared with ASI non-users, results of a pooled analysis presented at the 2014 Genitourinary Cancers Symposium has found.
The largest retrospective study to date to evaluate the role of ASIs—angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers—on outcomes found that this difference in the overall cohort, a median OS of 26.7 months versus 17.1 months (hazard ratio [HR], 1.21; 95% CI: 1.08-1.36; P = 0.0009) was even more pronounced among those receiving vascular endothelial growth factor (VEGF)-targeted therapy, 31.1 months versus 21.4 months (HR, 1.38; 95% CI: 1.16-1.64; P = 0.0003), said Rana R. McKay, a clinical oncology fellow at the Dana-Farber Cancer Institute, Boston, MA.
No similar effect was observed for those on mTOR-targeted (P = 0.298) or interferon-alfa targeted (P = 0.201) therapies, “suggesting a synergistic interaction between VEGF-targeted therapy and ASIs,” she said.
Noting that increasing evidence suggests angiotensin II modulates angiogenesis and tumorigenesis, the investigators analyzed 4,736 patients with mRCC treated on phase 3 (n = 6) and phase 2 (n = 6) Pfizer-sponsored trials between 2003 and 2013. Patients were treated with sunitinib (n = 1,059), sorafenib (n = 772), axitinib (n = 896), temsirolimus (n = 457), temsirolimus + interferon-alfa (n = 208), bevacizumab + temsirolimus (n = 393), bevacizumab + interferon-alfa (n = 391), or interferon-alfa (n = 560). ASI users were defined as patients taking an ASI at or within 30 days of initiation of therapy.
Patients were grouped as to whether they were hypertensive and receiving an ASI (n = 1,487); hypertensive and receiving a non-ASI (n = 783); or no antihypertensive use (n = 2,466). Baseline patient characteristics showed that the majority of patients were less than 65 years of age at initiation of therapy (69%), were male (69%), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (98%), had clear-cell histology (89%), and previous nephrectomy (70%). About one-third of patients (33%) had any prior systemic therapy. A total of 14% had International mRCC Database Consortium favorable-risk, 42% had intermediate-risk, and 24%, poor-risk disease. Baseline hypertension was present in 84% of ASI users, 81% of non-ASI users, and 16% of those with no antihypertensive use.
Lab-based and prospective studies are required to explore this relationship further in patients with mRCC, Dr. McKay said. For example, barring any contraindications, an ASI could be considered for those needing an antihypertensive, “especially in patients receiving VEGF-targeted treatments,” she added. Whether ASIs should be used for patients with mRCC without hypertension or other conditions that might warrant such treatment remains unknown.
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).