FTM. Great work. Where is folfirinox standing today? Significant lift over soc. appears to be the one BAVI needs to shoot for. Your insight is greatly appreciated
As a follow-up to this data I looked at one notable failure from these phase III trials. That is the Avastin phase III trial from which these plots of the effect of PS and disease extent originate. I looked at the phase II trial that prompted the phase III trial. So what went wrong? From the Kindler et al, 2010 paper on the phase III trial.
The single-arm phase II trial produced a MOS of 8.8 months for Avastin + gemcitabine, yet the phase III trial yielded a MOS of 5.8 months. The phase II and phase III trials used the same dosage and schedule of administration of gemcitabine and Avastin. The phase II trial enrolled 52 patients, the phase III trial enrolled 602 patients. Obviously the small number of patients in the phase II trial could be a contributing factor. The phase II trial enrolled only metastatic patients (100% stage IV), but the phase III trial enrolled locally advanced (16%) and metastatic (84%) patients. The biggest difference is the distribution of PS scores between the two trials. In the phase II trial the PS scores of 0, 1, 2 were 60%, 38%, 2%, whereas in the phase III trial these were 37%, 51%, 12% in the treatment arm and very similar in the control arm. So the percentage of PS = 0 and PS = 1 were reversed and more patients had PS = 2 in the phase III trial compared with the phase II trial. Just a cautionary note on how patient characteristics can affect the trial outcome. It may be that in some cancers this is more important than in others.