By Shreeya Nanda, Senior medwireNews Reporter
Australian researchers report that an alternating regimen of sunitinib and everolimus, although feasible and low-risk in patients with advanced renal cell carcinoma (RCC), failed to meet the prespecified criteria for use or continued development.
The team led by Ian Davis (Monash University Eastern Health Clinical School, Melbourne, Victoria) says that although the efficacy threshold was set high, with at least 84% of participants alive and progression free at 6 months, they believe that “such a level of activity needed to be demonstrated in order to alter practice and the trial was adequately powered to measure this”.
But the efficacy criteria was met by only 53% of the 55 patients with metastatic, locally advanced or locally recurrent inoperable disease given the EVERSUN alternating regimen, specifically open-label sunitinib 50 mg/day for 4 weeks with a 2-week break before switching to everolimus 10 mg/day for 5 weeks followed by a drug-washout period of 1 week.
Eighty percent of participants met the principal feasibility endpoint and started the second 12-week cycle of the alternating regimen within 14 weeks of the first day of cycle 1. And 64% remained on the alternating treatment for a minimum of 22 weeks.
After a median follow-up of 20 months, median progression-free survival was 8 months and median overall survival was 17 months.
The toxicity profile was consistent with that expected for each individual agent, say the researchers, with hypertension, anaemia, oral mucositis, fatigue, elevated gamma-glutamyl transferase, pain and lowered platelet count the most common grade 3 or higher toxicities.
Although Davis et al cannot conclude that the alternating strategy is inferior to sequential use, their findings suggest that “clinicians should maximise the value obtained from each line of treatment”, including the “judicious and careful assessment of dosing and treatment schedules where appropriate and where high level evidence supports such modifications.”
They emphasise in the Annals of Oncology: “Change to different agents should occur only when it is clear that the first line of therapy is no longer appropriate on the grounds of disease progression or unacceptable toxicity.”
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