Positive Preliminary Data Seen for Axitinib Plus Pembrolizumab in Renal Cell Carcinoma

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The combination of axitinib (Inlyta) plus pembrolizumab (Keytruda) can be added to the list of combination therapies that look promising in advanced renal cell carcinoma. In a phase Ib trial, almost three-quarters of patients with newly diagnosed advanced renal cell carcinoma treated with the combination achieved an objective response.1,2

ASCO Expert Sumanta K. Pal, MD, invited discussant of this study at the 2018 Genitourinary Cancers Symposium, called the duration of response of 18.6 months and the estimated progression-free survival of 21 months “unprecedented.” Dr. Pal was not involved in the study.

Michael Atkins, MD

Michael Atkins, MD

“The combination of axitinib and pembrolizumab is safe and tolerable in treatment-naive patients with advanced renal cell carcinoma. The antitumor activity of the combination is superior to that expected from axitinib alone or programmed cell death 1 monotherapy,” said lead author Michael Atkins, MD, of Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC.

Previous studies have shown efficacy with this type of combination, but also excess toxicity, said Dr. Atkins. Axitinib is a highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, so the authors hypothesized that it could be combined safely with pembrolizumab to achieve at least additive antitumor activity, and possibly synergy, in previously untreated advanced renal cell carcinoma.

Study Details

Dr. Atkins reported results of an open-label, phase Ib dose-finding and dose-expansion trial of newly diagnosed untreated patients with clear cell histology who had prior nephrectomy. At enrollment, all patients had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors, and biospecimens were required from all patients.

Patients received axitinib plus pembrolizumab and were treated until disease progression or unacceptable toxicity. Patients had computed tomography (CT) scans every 6 weeks. The dose-finding phase enrolled 11 patients. The maximum tolerated doses were axitinib at 5 mg twice daily and pembrolizumab at 2 mg/kg every 3 weeks.

Another 41 patients were added to the dose-expansion phase, for a total of 52 patients. The median age was 63 years, and more than 90% of patients were at intermediate or favorable risk. As of data cutoff, 25 patients were still on treatment, including 8 who had disease progression but were deemed to have “clinical benefit.” A total of 27 patients discontinued both study treatments (10 due to toxicity, 9 for disease progression, 5 for a mix of both, and 3 for other reasons). Patients who were taken off treatment for toxicity were censored at the last CT scan even if they were in response, Dr. Atkins noted.


  • The combination of axitinib and pembrolizumab shows encouraging preliminary responses in untreated advanced renal cell carcinoma.
  • The combination is being evaluated vs sunitinib in a phase III study.

The median duration of treatment was 14.5 months. About 61% required dose reductions of axitinib for at least two consecutive doses. The mean and median daily doses of axitinib were 8.2 mg and 8.8 mg, respectively; the mean and median daily doses of pembrolizumab were 1.9 mg/kg and 2.0 mg/kg, respectively.

Of 52 patients, 38 (73%) had objective responses, and 4 (7.7%) had complete responses. Another 8 patients had stable disease during combination therapy. Three patients had indeterminate responses, and three had progressive disease as their best response. At data cutoff, 19 of 38 responders continued to respond. The median duration of tumor response was 18.6 months.

The median progression-free survival was estimated as 21 months, Dr. Atkins said. Median overall survival was not yet reached, with 90% of patients alive at 18 months. There were six deaths, four due to progressive disease, and two unrelated to renal cell carcinoma.


Approximately 65% of patients had grade 3 or greater toxicities, and most were related to axitinib. The most common event was hypertension (23%), followed by fatigue (9.6%) and diarrhea (9.6%).

“There were fewer liver function abnormalities and less fatigue [with this combination] than reported with other VEGFR/immunotherapy combinations,” Dr. Atkins noted. The ongoing phase III KEYNOTE N426 trial is comparing axitinib/pembrolizumab vs sunitinib in advanced renal cell carcinoma. ■

DISCLOSURE: Dr. Atkins has had a consulting or advisory role with Acceleron Pharma, Agenus, Alexion Pharmaceuticals, Argos Therapeutics, Array BioPharma, AstraZeneca/MedIummune, Bristol-Myers Squibb, Celldex, Eisai, Exelixis, Genentech, Genoptix, Glactone Pharma, Idera, Merck, Nektar, Novartis, Peleton, Pfizer, and X4 Pharma and has received honoraria from Bristol-Myers Squibb. Dr. Pal reported no conflicts of interest.


1. Atkins MB, Plimack ER, Puzanov I, et al: Safety and efficacy of axitinib in combination with pembrolizumab in patients with advanced renal cell cancer. 2018 Genitourinary Cancers Symposium. Abstract 579. Presented February 10, 2018.

2. Atkins MB, Plimack ER, Puzanov I, et al: Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: A non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol 19:405-415, 2018.

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