A phase 2 study testing individualized axitinib dosing in patients with metastatic renal cell carcinoma (RCC) who had previously been treated with checkpoint inhibitors failed to meet its prespecified threshold for progression-free survival — but the study authors showed that the individualized titration scheme is feasible, and resulted in robust clinical activity.1

The study included 40 patients with locally recurrent or metastatic RCC who received oral axitinib at a starting dose of 5 mg twice daily with titration every 14 days in 1 mg increments as long as there was no axitinib-related grade 2 or higher mucositis, diarrhea, hand-foot syndrome, or fatigue present in patients.

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The median daily dose given in the study was 5 mg twice daily, with a maximum dose of 9 mg twice daily.

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About one-third of patients required a dose reduction to less than 5 mg twice daily.

With a median follow-up of 8.7 months, median progression-free survival was 8.8 months. This failed to meet the primary endpoint, which targeted a 45% increase in median progression-free survival from retrospective review data (6.5 months) to 9.5 months.

Forty-five percent of patients achieve an objective response, with 1 patient achieving a complete response and 17 achieving a partial response.

The most commonly occurring adverse events were fatigue (83%) and hypertension (75%). The most common grade 3 adverse event was hypertension (60%).

“The novel dosing scheme in this study provides a clinically relevant framework to guide optimal dosing of axitinib for metastatic renal cell carcinoma patients,” the researchers wrote. “The high clinical activity with low high-grade toxicity is a reflection of this and this regimen could be immediately translatable to clinical practice.”

In an accompanying editorial,2 Camillo Porta, of IRCCS Istituti Clinici Scientifici Maugeri, Italy, and Manuela Schmidinger, of Medical University of Vienna, questioned whether this study were supported by a scientific rationale, or if it is “just an attempt to generate prospective data on an established agent in a new therapeutic setting.”

“Withholding axitinib or intermittent dosing in the case of progression could spare the patients relevant toxicities, without necessarily hampering treatment activity,” they wrote. “More academic — and less marketing-driven — studies are strongly warranted to answer these key questions and to optimize treatment outcomes for patients with metastatic renal cell carcinoma.”

Disclosure: The primary study was funded by Pfizer. For a full list of disclosures, please refer to the original study.


  1. Ornstein MC, Pal SK, Wood LS, et al. Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicenter, single-arm, phase 2 study. Lancet Oncol. doi: 10.1016/S1470-2045(19)30513-3
  2. Porta C, Schmidinger. Renal cell carcinoma treatment after first-line combinations [published online August 16, 2019]. Lancet Oncol. doi: 10.1016/S1470-2045(19)30510-8