I've previously described the novel "pan-HER inhibitor" PF-299804 and even the randomized phase II trial of PF-299 vs. the EGFR tyrosine kinase inhibitor Tarceva that showed a higher response rate (RR) and longer progression-free survival (PFS) with PF-299. At the World Conference on Lung Cancer in Amsterdam, the investigators also presented updated results from this trial that showed a trend toward a survival benefit with PF-299 as well.
This was a trial of 188 patients with previously treated advanced NSCLC, not selected for having an EGFR mutation, being never smokers, or any other specific subset. The prior post describes many of the results, including the modestly greater side effects with PF-299 that accompanied the improvement in RR and PFS. In the update of the results, PFS is still significantly better with PF-299, and they also specifically focused on the 2/3 of patients who were KRAS "wild type" (no mutation), who are shown in the curves on the right in the figure below:
As you can see, there was a pretty convincing (and statistically significant) shift to more prolonged PFS in entire patient population that was even more pronounced in the patients who were KRAS wild type.
As in the earlier presentation of the results from the trial, a review of the various subsets of patients in the trial showed that nearly all subgroups trended toward more benefit in PFS with PF-299 compared with Tarceva:
In the figure above, the boxes situated to the left of the vertical line on the right side represent improvement with PF299 over Tarceva (and the more to the left, the stronger the benefit). Nearly all groups fall clearly to the left of the vertical line.
At the Amsterdam meeting, we also got results on overall survival (OS), which showed a trend (not statistically) significant that also favored PF-299, as shown in the figure below:
Though it shows only a trend in the direction of more favorable direction, this was only a relatively small phase II trial, for which showing a statistically significant improvement in OS would have been very ambitious.
Overall, the investigators were very encouraged by these findings, but the definitive answer about the potential benefit of PF-299804 over Tarceva will ultimately be answered by the results of the phase III trial (ARCHER 1009) with the same general study design that is currently ongoing. This trial will be looking for a significant improvement in PFS in both the general population of all NSCLC patients and in the subset of patients with KRAS wild type. I'll look forward to presenting results of that trial in coming years, and this could lead to a new agent becoming available for advanced NSCLC.