PFShhh.

Top Line: PFS, perhaps it’s no coincidence this stands for both progression-free survival and the sound one makes when not impressed.

The Study: PFS is entering the cross-hairs of skeptics everywhere. Some of the most vitriolic reactions appear to be towards bevacizumab. Why? Well, it seems that bev in particular has a track record of giving the appearance of disease response or stability while essentially putting little to no dent in survival and a big dent in healthcare spending. Not to mention it undermines our “worldview” of what a cancer therapy is supposed to do: shrink disease to improve survival. But are we Galileo or the Pope in this current era of scientific discovery? Let’s take two recent trials in the head and neck realm. In one, adding bev to chemo improved PFS but not overall survival (OS). In the other, pembrolizumab did not improve PFS yet clearly improved OS. And there’s no clear explanation of why. Enter this huge whole genome sequencing analysis of primary and metastatic lesions. The breadth and depth of genomic instability was staggering—ranging from single nucleotide variations to major changes in the overall structure of the genome. In fact, over half of metastatic lesions had whole genome duplication. So while Merck and the FDA are debating whether some niche targeted agent produces a measurable tumor response, cancer cells are over here making a full-on second genome.

TBL: In the battle of evolutionary design versus “intelligent” design, we might not be as smart as we think. | Priestley, Nature 2019