Daraxonrasib in pancreas cancer.

RASolute 302 trial has rightly generated significant excitement at ASCO2026 and I share this excitement. Pancreatic cancer has for long been a challenge for oncologists and KRAS is the classic ‘undruggable’ target. Any advance here is notable and must be celebrated. However no trial is perfect and an honest appraisal will help design better studies and develop safer and more effective therapies. It is in this spirit that I delve into the details of trial.

I have just four points

1. 100% of people on the experimental drug eventually progress. There is no curative subset. This is disappointing and different than other agents such as immunotherapy, where there can be cures.

2. 15% of the control arm declines treatment but only 3% of the intervention arm does not recieve therapy. A difference of 12%. These people are likely not random dropouts but the highest socioeconomic status participants with best alternatives. The drop out is patient disappointment. Thus randomization is violated. We potentially have the bottom 9/10 participants (in terms of OS) compared against 10/10. (not all of these persons appear to be censored, which is good, but many are).

3. Gains in OS exceed PFS gains. This raises the question of whether experimental drug is followed by chemo while chemo is followed by hospice or some other palliative option. Thus some of the gains of the experimental drug may be due to this additional care. Yet post protocol treatments not reported to explore this further. Neither in the paper nor the supplemental appendix. This is unfortunate.

4. Daraxonrasib will be harder to give older frailer people due to side effects.

Overall: A significant step forward for patients with metastatic pancreatic cancer but much more needs to be accomplished for this disease. I hope this is only the first of other advances to come in the future.

Also continued best wishes to Ben Sasse whom I have long admired.