The following article is part of conference coverage from the 2018 Genitourinary Cancers Symposium in San Francisco. Renal and Urology News’ staff will be reporting live on medical studies conducted by urologists and other specialists who are tops in their field in kidney stones, prostate cancer, kidney cancer, bladder cancer, enlarged prostate, and more. Check back for the latest news from GU 2018.

SAN FRANCISCO—Dual treatment with axitinib and pembrolizumab is safe and tolerable and exhibits promising antitumor activity in previously untreated patients with advanced renal cell carcinoma (RCC), investigators concluded in a presentation of study data at the 2018 Genitourinary Cancers Symposium

Michael B. Atkins, MD, of the Georgetown University Lombardi Comprehensive Cancer Center in Washington, DC, and colleagues explained that previous studies looking at combining programmed death-1 (PD-1) checkpoint inhibitors with tyrosine kinase inhibitors of the vascular endothelial growth factor (VEGF) pathway have been characterized by excess toxicity, thus precluding further development. They hypothesized that combining axitinib, which is a more selective inhibitor of the VEGF pathway, with pembrolizumab, a PD-1 inhibitor, would be well tolerated and have antitumor activity in treatment-naïve patients with advanced RCC. Study findings suggest this is the case.

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“The antitumor activity of the combination is superior to that expected from axitinib or PD-1/PD-L1 pathway inhibitor monotherapy,” Dr Atkins told attendees.

In an open-label phase Ib study, Dr Atkins’ team enrolled 52 treatment-naïve patients with advanced RCC from September 24, 2014 to October 13, 2015. The study consisted of a dose-finding phase to determine the maximum tolerated dose and dose expansion phase. Axitinib 5 mg was administered orally twice daily, with pembrolizumab 2 mg/kg administered intravenously every 3 weeks. The investigators assessed tumors using RESIST v1.1 criteria at baseline, week 12, and every 6 weeks thereafter. The primary end point was dose-limiting toxicity (DLT) during the first 2 cycles (6 weeks). Secondary end points included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

The investigators observed no unexpected toxicities. Three DLTs were reported among 11 patients treated in the dose-finding phase: 1 transient ischemic attack and 2 episodes in which less than 75% of the planned axitinib dose was administered because of treatment-related toxicity.

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At a cutoff date of March 30, 2017, 25 patients were receiving study treatment. The most common (occurring in at least 10% of patients) grade 3 or higher all-cause adverse events included hypertension (23%), diarrhea (10%), and fatigue (10%). Most common (greater than 10%) potentially immune-related AEs included diarrhea (29%), increased alanine aminotransferase (17%) and aspartate aminotransferase (13%), hypothyroidism (13%), and fatigue (12%). The ORR was 73.1% (95% CI 59.0–84.4) Median PFS was 20.9 months (95% CI 15.4–no evaluable). The authors noted that OS data were not mature at a minimum follow-up period of 17.6 months, with 6 treatment-unrelated deaths reported.

A phase 3 trial is underway comparing the combination therapy with suninitib monotherapy.

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Atkins MB, Plimack ER, Puzanov I, et al. Safety and efficacy of axitinib (axi) in combination with pembrolizumab (pembro) in patients (pts) with advanced renal cell  carcinoma (aRCC). Presented at the 2018 Genitourinary Cancers Symposium, held in San Francisco from Feb. 8-10. Abstract 579.