Action to Cure Kidney Cancer

Cezary Szczylik from the Military Medical Institute, Warsaw, Poland, made an oral presentation of a randomized, multi-institutional, Phase 2 trial of first-line treatment with Nexavar versus Interferon. All patients had clear cell pathology. This was a dose escalated trial separated into two phases, the first before tumor progression, and the second after tumor progression. This was a two-arm trial, which, for Period 1, 97 patients received the standard Nexavar dose of 400 mg twice a day on the first arm, and 92 patients received Interferon on the second arm. After progression, for Period 2, the Nexavar arm was upped to 600 mg twice a day, and the Interferon arm was crossed over to Nexavar at 400 mg twice a day. The primary endpoints were progression free survival (PFS) and quality of life.

Period 1 Results

There were a couple of complete remissions with Interferon but none with Nexavar. Nexavar patients reported a higher quality of life than Interferon patients. Hand-foot syndrome was the major (11%) grade 3 event for Nexavar. For Nexavar, the investigators found a positive correlation between the drop in levels of the biologic marker sVEGFR and PFS.

For Period 2, 44 patients progressed under Nexavar and were dose-escalated to 600 mg twice a day. 50 patients under Interferon and were crossed over to Nexavar, but 6 dropped out leaving 44 patients to be evaluated.

Period 2 Results

The tumor shrinkage was by investigator assessment.

There was no increase in grade 3/4 adverse events for the patients who were dose-escalated from 400 mg to 600 mg. The group that went from Interferon to Nexavar did incur grade 3/4 events: fatigue (14%), diarrhea (12%, hand-foot syndrome (10%).

Dr.Szczylik summarized Period 1 noting that the PFS for Nexavar and Interferon were the same. This result, at 5.7 months does not agree with other Nexavar studies presented at this year's ASCO, which are around 9 months. Both tumor shrinkage and quality of life were higher with Nexavar than with Interferon. For Period 2, the PFS for the crossover group, 5.7 months, was similar to the 5.5 months PFS for the Phase 3 second-line TARGET trial (the one that got the original FDA approval for Nexavar and which was updated by Dr. Bukowski this year). The dose-escalated arm was well tolerated, showed further delay in progression, and maintained quality of life.

Robert Figlin was the discussant. He said that, based on the results of this trial and the trials of Sutent versus Interferon and Torisel versus Interferon reported at last year's ASCO and Avastin plus Interferon versus Interferon reported at this year's ASCO, we now have proof that Nexavar is inferior to other available therapies in a first-line setting.

Reporter's comment: this trial showed that Nexavar has some effectiveness as a dose escalated therapy, and it confirmed the results of the TARGET trial, which showed efficacy of Nexavar as a second-line therapy in cytokine refractory patients. But neither Dr. Figlin nor other oncologists at ASCO mentioned the fact that other targeted agents such as Sutent and Axitinib have had better results than Nexavar in second-line, cytokine-refractory trials.

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