Practice-changing
STAMPEDE (abiraterone ± enzalutamide, high-risk non-metastatic) NCT00268476
ForHigh-risk M0 prostate: node+ or ≥2 of T3-4/Gleason 8-10/PSA≥40
TL;DRMFS HR 0.53 (6yr 82% vs 69%) and OS HR 0.60 adding 2yr abiraterone to ADT in high-risk M0 prostate (85% also had RT).
The RT read: abiraterone sits on top of definitive ADT+RT (74Gy/37fx to prostate+SV in the 85% who got RT), not RT vs no-RT. It moves systemic intensification for the high-risk M0 pt you're already irradiating; enzalutamide adds nothing over abiraterone (interaction HR 1.02, p=0.91).
8 details 2 trials watching
Pooled meta-analysis of two open-label phase 3 RCTs within the STAMPEDE platform, 113 UK/Swiss sites, N=1974, randomized 1:1. Median follow-up 72 mo (60-84).
High-risk non-metastatic disease: node-positive, or if node-negative ≥2 of T3/T4, Gleason 8-10, PSA ≥40; or high-risk relapse. Median age 68, median PSA 34; 39% node-positive.
Abiraterone 1000mg + prednisolone 5mg daily for 2yr added to 3yr ADT; the second trial's combination arm also received enzalutamide 160mg. Control = ADT alone.
RT planned in 85% (1684/1974): 74Gy/37fx to prostate + seminal vesicles or hypofractionated equivalent. Mandated if node-negative, encouraged if node-positive.
Primary: metastasis-free survival. Secondary: OS, prostate cancer-specific survival, biochemical failure-free survival, PFS, and toxicity.
Adding enzalutamide to abiraterone gave no extra MFS benefit (interaction HR 1.02, p=0.91), with no between-trial heterogeneity.
Open-label design, though MFS/OS are hard endpoints less prone to ascertainment bias. Pooled across two platform trials; no radiotherapy-treated subgroup HR reported in the source excerpt.
Two randomised phase 3 trials pooled; MFS primary hit (HR 0.53) with concordant OS benefit at 72mo, applicable high-risk M0 population. Adding enzalutamide gave no extra benefit.
In high-risk M0 prostate (node+, or ≥2 of T3-4/Gleason 8-10/PSA≥40) going to definitive ADT+RT, this supports adding 2yr abiraterone; it does not extend to lower-risk localized disease, and adding enzalutamide buys nothing.
- Optimal duration of abiraterone (2yr fixed used here)
- Whether benefit holds when radiotherapy is omitted
- Long-term OS and cure fraction beyond 72 months recruiting A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation Phase 3n=700 · primary completion 2033-03 · MFS endpoint, high-risk localised, 2033 readoutrecruiting Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer Phase 2n=140 · primary completion 2033-04 · abi added to ADT+RT in localised, 2033 readout
📚 Sources · 📄 1 paper
RASolute 302
ForPreviously treated metastatic pancreatic cancer (RAS-mut or WT)
HR 0.40
95% CI 0.30-0.53, P<0.001; mOS 13.2 vs 6.7 mo (overall pop)
TL;DRmOS 13.2 vs 6.7mo, HR 0.40 (0.30-0.53), P<0.001 for daraxonrasib vs investigator's-choice chemo in previously treated metastatic pancreatic cancer.
In previously treated metastatic pancreatic cancer with a RAS mutation, daraxonrasib's OS benefit supports it as a systemic option over chemotherapy; the signal does not extend to treatment-naive or localized disease.
| Population · Arm | Median OS | HR (death) | 12-mo OS |
|---|---|---|---|
| G12 · Daraxonrasib | 13.2 mo (10.0-NR) | 0.40 (0.30-0.54) | 53.3% |
| G12 · Chemo | 6.6 mo (5.4-8.2) | — | 8.7% |
| Overall · Daraxonrasib | 13.2 mo (10.0-NR) | 0.40 (0.30-0.53) | 53.2% |
| Overall · Chemo | 6.7 mo (5.8-8.0) | — | 17.3% |
7 details 1 trial watching
Phase 3 RCT, daraxonrasib vs investigator's-choice chemotherapy in previously treated metastatic pancreatic cancer. Two prespecified populations: RAS G12-mutant and overall (G12/G13/Q61 or no RAS mutation identified).
Previously treated metastatic pancreatic cancer. RAS G12 arm n=228 vs 231; overall n=248 vs 252. Overall population also includes tumors with no identified RAS mutation.
Daraxonrasib, an oral RAS(ON) multi-selective inhibitor targeting active GTP-bound RAS, vs investigator's choice cytotoxic chemotherapy.
Primary OS met: median 13.2 vs 6.7 mo, HR 0.40 (0.30-0.53), P<0.001 (overall); HR 0.40 (0.30-0.54) in RAS G12. 12-mo OS 53% vs 17% (overall). Deaths 32% vs 55-56%.
Chemo control (6.6-6.7 mo) matches the historic 2L metastatic PDAC benchmark; no prior targeted agent has shown an OS signal of this magnitude in this setting.
Data limited to a single ASCO LBA OS figure; full safety and PFS not yet reported. Open-label; daraxonrasib median OS upper CI not reached (10.0-NR), so tail durability is immature.
Randomized phase 3, OS primary hit HR 0.40 in 2L metastatic PDAC where no targeted SOC exists; hard endpoint, unprecedented magnitude. Full LBA data pending.
- Sequencing and combination with 1L chemotherapy recruiting Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Phase 3n=900 · primary completion 2028-06 · 1L daraxonrasib + gem/nab-paclitaxel combination
- Efficacy across RAS-WT vs RAS-mutant subsets
- Full safety and toxicity profile
📚 Sources · 🐦 1 tweet
#ASCO26
— Nicholas Hornstein (@GIMedOnc) May 31, 2026
This one is special.
This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.
Let’s dive in.
RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer
Abstract LBA5 (soon!)… pic.twitter.com/Lq7PEjOWAo