Delay Dose Escalation of Axitinib in Metastatic RCC?

Delaying dose escalation of axitinib until disease progression in patients with metastatic renal cell carcinoma (RCC) may be a viable treatment strategy, and a preferred option in patients with concerns about drug-related toxicity, quality of life optimization, or healthcare associated costs, according to the results of a retrospective study.

Axitinib is currently the standard of care for patients with metastatic RCC, and is dosed at 5 mg twice daily with escalation to 7 mg and 10 mg after consecutive 2-week intervals as tolerated. In the study, researchers led by Gary Joseph Doherty, MD, of Cambridge University Hospital NHS Foundation Trust, tested an alternative dose escalation strategy. This “pragmatic” strategy only escalates the dose of axitinib after disease progression or where rapid responses were clinically required.

“This strategy was adopted after our early clinical experience which suggested that our patient population tolerated higher doses of axitinib less well than the population treated within the AXIS trial, as well as unambiguous clinical responses being achieved at the starting dose of 5 mg twice daily,” the researchers wrote in ESMO Open.

They looked at electronic health records and radiology results of 42 patients treated at Addenbrooke’s Hospital in Cambridge, United Kingdom, in whom this strategy was used. Of the 42 patients, 29 had one or more dose escalation events. Overall, 60 dose escalation events were identified, with a median of two per patient. The objective radiological consequences of 53 of these events could be analyzed.

Disease control rate was similar after the first dose escalation events and the second event (68.8% vs 70.0%). More than half of all dose escalation events (DEE), and more than 60% of events made because of disease progression resulted in disease control.

The median overall survival from initiation of axitinib for all dose-escalated patients was 19.9 months and 16.5 months for the entire cohort of patients.

“While ours is a small, retrospectively reviewed cohort, we believe that the outcomes for the patients presented here supports cautious, clinically guided dose escalation of axitinib, particularly in clear patients with whom there are specific concerns about axitinib-related drug toxicity (although prospective toxicity data were not collected in our study), quality of life or drug-related cost,” the researchers wrote. “Thirty-one percent of patients undergoing DEEs in this study required dose reductions from their starting dose as the first dose modification event, underlining our concerns with axitinib tolerance in real-world patient populations.”

Commenting of the results, Moshe Ornstein, MD, of the Cleveland Clinic, said it is well known the tyrosine kinase inhibitor dosing in metastatic RCC patients is extremely individualized.

“In clinical practice, we always try to gain as much benefit as we can from every anti-cancer therapy we have for our patients. Having data to support that disease control is possible after disease progression with a higher dose of the same therapy is critical,” Ornstein told Cancer Network.

“These data tell us two important clinically meaningful points. Firstly, if patients are tolerating axitinib and develop disease progression, a continuation of axitinib at a higher dose can be attempted in appropriate patients prior to switching to a subsequent therapy. Likewise, these data inform us that patients who are judged to potentially not tolerate early axitinib dose-escalation may consider an approach in which dose escalation is reserved until they develop disease progression.”