"Totally agree, all arguments you mentioned point to success of METEOR, my slight concern is a dose (60 mg)"
You're going to have to trust me on this because I don't think its published or archived anywhere. Dr Toni Choueri was the lead investigator for the original RCC trial. I recall him commenting on the dose issue. By the time the RCC trial was initiated, the investigators were aware of the prior dosing and tolerability issues. His comment was that the trial protocol called for 100mg, but also allowed for titration to a lower dose, so those rules were generously interpreted and he left the impression that patients were immediately titrated lower before tolerability became a problem.
The RCC Cabo ph 1 had only 25 patients. The topline result was PFS of 13 months and OS of 15 months. For comparison, in its registrational frontline study, Sutent had PFS of 11 months, but OS was 26 months. The 13 month PFS enjoyed by the Cabo patients looks a bit suspect to me, especially considering the apparently short survival following progression. I just wish we had a larger sample size to consider. All said, while I don't expect the Meteor result to mirror the phase 1 experience, improving on the Afinitor 5 month standard is a relatively low hurdle. We'll see soon enough.
"PFS was a secondary endpoint and visceral data and time to SRE are at most exploratory."
I have to agree. Cabo is a nonstarter in CRPC. The visceral mets data is at best informative for a future trial. If I remember correctly, only about 30% of patients present with visceral mets, so the commercial opportunity is a fraction of that sought with the Comets. The SRE data is also interesting, but if EXEL wants to present Cabo as a bone drug, it is a long road and rather than comparing those results vs an abi control it would be more appropriate to make comparisons to XGeva and Alpharadin. The overall HR=.90 is consistent or marginally better than those seen with other VEGF inhibitors tested in CRPC (Sutent and Avastin). Factor in the failure of Comet 2 and it further degrades the argument for a benefit not captured in the survival data.
Though disappointing, the results are still informative. RCC will sink or swim based on PFS with the proviso that OS is not negatively impacted. Two phase 3 trials (Exam and now Comet 1) have demonstrated highly significant improvements in PFS with numeric (but nonsignificant) improvement in OS. Granted, Meteor has an active comparator (Afinitor), which showed a 5 month PFS in its registrational study. However, recently published evidence shows that sequential VEGF TKI's achieve a superior result to Afinitor. My opinion is that the recent run up is attributable to positive expectations for the Meteor analysis which is either ongoing or soon to start.