Search
Dose-Escalated Nexavar
Robert Amato of Methodist Hospital in Houston, TX made an oral presentation of a Phase 2, single-center trial of dose-escalated Nexavar in kidney cancer patients. The recommended dose for Nexavar is 400 mg bid (twice daily) based on previous trial data. This trial was designed as a single-arm trial to test the safety and toxicity of the dose-escalated therapy with secondary endpoints of response rate, progression-free survival and overall survival. The patients had to have a component of clear cell in their pathology. 43% had prior cytokine treatment while 57% were treatment naïve (this was their first treatment). The plan called for 400 mg bid for days 1-28, 600 mg bid for days 29-56, and 800 mg bid for days 57 and beyond with dose modification for grade 3/4 toxicity.
44 patients (pts) started the therapy at 400 mg bid, and 3 pts required dose reductions. 41 pts were escalated to 600 mg bid at day 29. At day 57, 32 pts were escalated to 800 mg bid. Of these, 7 pts had to be reduced in dose, so 25 pts remained on the highest dose of 1600 mg per day.
The major grade 3/4 toxicities were hand-foot syndrome and diarrhea. The longer the trial, the more patients seemed to tolerate the effects of the therapy. Also, patients showing early toxicity had trouble being escalated later on.
Dose-Escalated Nexavar Results
|
Type of Response |
Responses |
|
Complete Response |
7 (16%) |
|---|---|
|
Partial Response |
17 (39%) |
|
Stable Disease |
9 (20%) |
|
Progressive Disease |
11 (25%) |
Median progression free survival is 8.4 months. There are still 16 people active on the study. Overall survival hasn't been reached.
Dr. Amato's conclusions were that dose-escalated Nexavar was well tolerated as 93% of patients were escalated to either 1200 mg or 1600 mg a day, and there was a high level of anti-tumor activity given a 55% overall response rate. Note that the response rates are still to be confirmed by an independent lab, in this case Yale University. They are adding another 30 patients to their study, and other sites are planning similar studies.
Robert Figlin was the discussant for this presentation. He was a little skeptical of the trial results and said that they should be independently confirmed and should also be duplicated in other larger trials by independent investigators. If they are confirmed it would be great, because Dr. Figlin said that the response data presented by Dr. Amato were superior to any other data that we've seen in targeted therapy in kidney cancer. Furthermore, if the results are confirmed, then Dr. Figlin suggested that Nexavar's manufacturers, Bayer and Onyx, run a Phase 3 trial to test dose escalation rather than leaving it to the investigators themselves to take the initiative.