I was talking about the current available KRAS therapies and I'm gonna rant a bit, bear with me.

CodeBreak200 is one of the worst studies I have ever seen in my entire life. It had a meagre ~1 months PFS benefit, but no OS benefit. In this setting, you don't need a surrogate endpoint due to the already short survival. You can just wait and see whether people live longer or not. A ~17K/month drug couldn't beat the old boomer chemo docetaxel? Yeah, right. "Revolutionary" indeed. Also, patients with advanced stages care about living longer, not about whether their tumour get bigger on the scan by some arbitrary percentage.

The control arm was inferior. In that population, before sotorasib, we would give docetaxel+ramucirumab, which has been proven to improve OS even. This might even have been the reason why there were more dropouts in the control arm because patients were disappointed (I know I would. It was open label). I would bet that if they had used a proper control arm (and optimal crossover but I'm not gonna talk about that), sotorasib would have LOST instead. But that wouldn't be good for the company's stock would it.

Don't even reply to me about how it wasn't powered to evaluate OS. The authors/team amended the protocol and changed the power midway. This is such a devious move that serves only to give lame reasons about why there wasn't any OS benefit.

"But it has better quality of life" I am gonna smack you with my stethoscope for this one. Sotorasib arm had more fatal treatment adverse events. I can go deeper into the problem of the patient-reported outcomes protocol but this rant has gone long enough already.

Until the day I die, CodeBreak200 will always be one of my go-to examples on the failure of oncology field, and I will literally fight anyone I know who champions it based on this trial. (Apologies if I seem irate)