Here is a reason why the NAPOLi trial was done comparing Nalirifox to Gemzar/Abraxane first and not to Folfirinox. The first goal of a clinical trial is to prove an investigational new drug or drug combo (IND) is more effective then a currently approved drug. If it is, it gets approval-if not, then it doesn’t unless it shows it is at least equivlent in effectiveness with less side effects and adverse reactions are of a lower grade than the drug or regimen it is compared against.

If Nalirifox was first compared to Folfirinox and found it was not better, then it wouldn’t receive approval. However, if it was proved first that Nalirifox outperformed G/A in a number of metrics and side effects and adverse events were better, it could be approved and patients could begin gaining benefit. Now the next step is in a comparison with Folfirinox to see if is better. Some of those questions might already be answered looking at the Waterfall plots and Meier-Kaplan data and other statistical metrics in comparing with G/A. Those same metrics already exist between Folfirinox and G/A and can be interpreted as to whether study is warranted now between Nalirifox and Folfirinox.

With respect to efficacy of Oxaliplatin and cis-platin, there were comparison studies done more than a decade ago comparing the two. Oxaliplatin was found to be more effective in providing more overall survival and progression free survival but does have more neurotoxicity. Between 30-35% of treatment cohorts respond to either Folfirinox or Gemzar/Abraxane. It could just as well have been that you did not respond to 5-FU and not the Oxaliplatin.