GI Upper
2026-11-04 ESMO Congress 2026
SANO
ForLocally advanced oesophageal cancer, cCR after nCRT
TL;DR5y OS 50% vs 54%, HR 1.17 (0.77-1.77) active surveillance vs surgery after cCR to nCRT; distant mets 46% vs 29%, P<.01.
The RT read is that nCRT alone was the definitive treatment for 43% of the surveillance arm, but distant mets rose to 46% vs 29% without immediate surgery. That makes cCR after nCRT a reasonable organ-preservation endpoint for selected pts. Whether early oesophagectomy suppresses distant spread, or the gap comes from how surveillance detects disease, is the open question.
In locally advanced oesophageal cancer with cCR on biopsies, EUS and PET-CT after nCRT, this supports active surveillance with surgery as needed as a discussable option; it does not address pts without cCR or nCRT regimens other than those used in SANO. The longer read
nCRT alone was definitive treatment for a large part of the surveillance arm, which makes cCR on biopsies, EUS and PET-CT the decision gate. The nCRT regimen is not stated in source, so dose transfer cannot be judged, and the distant-mets excess (46% vs 29%) matters when counselling responders.
Surgery as needed spared 85/198 (43%) a non-beneficial oesophagectomy with no significant 5y OS difference (HR 1.17). The distant-mets excess under surveillance (P<.01) raises the question of whether delaying resection gives up systemic control, and that 43% includes pts who progressed within 6 mo.
9 details 1 trial watching
Multicentre stepped-wedge cluster-randomised non-inferiority trial, 2017-2021, Netherlands Trial Register NTR-6803. This report covers 5y outcomes at median f/u 76 mo (IQR 67-86).
Locally advanced oesophageal cancer with a complete clinical response after nCRT, defined as no tumour on endoscopic biopsies, endoscopic ultrasound, or PET-CT. N=309: 198 active surveillance, 111 standard surgery.
nCRT was the common backbone. The regimen, dose and fractionation are not stated in source, so whether the result transfers to a given chemoRT protocol cannot be judged from this abstract.
The earlier report showed non-inferiority on two-year OS with improved QoL under surveillance. This analysis compares 5y OS and DFS by Cox regression and estimates distant metastasis incidence with competing-risk analysis.
OS and DFS were not significantly different, but distant mets were higher under surveillance (P<.01). 85/198 (43%) were spared non-beneficial oesophagectomy.
| Endpoint | Active surveillance (n=198) | Standard surgery (n=111) | Effect |
|---|---|---|---|
| 5y OS | 50% (95%CI 34-57) | 54% (95%CI 46-64) | HR 1.17 (95%CI 0.77-1.77) |
| DFS | not reported per arm | not reported per arm | HR 1.39 (95% CI 0.94-2.06) |
| 5y cumulative incidence distant mets | 46% (95%CI 39-53) | 29% (95%CI 21-37) | P<.01 |
This extends SANO's own 2y non-inferiority result and follows the preSANO cCR-assessment framework. It parallels the watch-and-wait paradigm in rectal cancer (OPRA). The randomised definitive-CRT question is being tested separately in NEEDS.
The 43% spared figure counts pts with distant mets within 6 mo of nCRT, which inflates the organ-preservation benefit. At 5y, no NI margin is reported, and an OS HR upper bound of 1.77 cannot exclude clinically relevant harm.
Survival parity holds at 5y, but the distant-mets excess is the signal to explain. It could reflect micrometastatic seeding during delayed resection, or disease surfacing on surveillance imaging that resection would have found later. The abstract cannot separate the two.
Long-term f/u of a cluster-randomised NI trial supporting emerging organ preservation; wide OS CI and a significant distant-mets excess stop short of practice-changing.
- Why are distant metastases higher under active surveillance?
- Does systemic therapy during surveillance offset the distant-mets excess? recruiting An Organ Preservation Strategies After Chemoradiotherapy Combined With Immunotherapy for Esophageal Cancer (PALACE3). Phase 3n=356 · primary completion 2028-03 · ph3 nCRT+IO organ preservation vs nCRT+surgery, 3y OS
- Which nCRT regimen maximizes durable cCR?
📚 Sources · 📄 2 papers
Abstract
Abstract
2026-11-02
AGITG MASTERPLAN
ForHigh-risk operable, borderline resectable, or locally advanced pancreatic cancer
20.2% vs 52.0%
P=0.022
TL;DR12-mo locoregional recurrence 20.2% vs 52.0% (P=0.022) adding SBRT 40 Gy/5fx to chemo in high-risk operable, borderline, or locally advanced pancreatic cancer.
Reported via OncoDaily →
The LRR benefit held in the potentially operable stratum (19.7% vs 52.9%, P=0.031) but not the inoperable one (P=0.16, n=26), so the strongest RT read is neoadjuvant SBRT 40 Gy/5fx after 3 mo of modern chemo in borderline or high-risk operable disease. That benefit came despite only 80% of the SBRT arm starting RT.
In borderline resectable or high-risk operable pancreatic cancer after 3 mo of mFOLFIRINOX or gem/nab-paclitaxel, this supports considering SBRT 40 Gy/5fx before surgical reassessment; the inoperable-stratum signal is too small to settle locally advanced disease. The longer read
SBRT 40 Gy/5fx after 3 mo of modern chemo cut 12-mo LRR to 19.7% vs 52.9% in potentially operable disease (P=0.031), despite 80% SBRT uptake. The inoperable stratum (P=0.16, n=26) leaves locally advanced SBRT unsettled.
Neoadjuvant SBRT gave numerically higher resection (68% vs 59%, P=0.54) and R0 (62% vs 40%, P=0.44) in potentially operable pts. Neither difference is significant, so this does not yet show SBRT improves resectability, but it shows no surgical penalty.
11 details 4 trials watching
Randomized 2:1, chemo + SBRT vs chemo alone, 75 enrolled and 74 eligible across 14 centers. Phase not stated in source.
Potentially operable (n=48): borderline resectable, or operable with tumor >4 cm, extrapancreatic extension, or nodal involvement. Inoperable (n=26): locally advanced or medically inoperable.
Three months of mFOLFIRINOX or gemcitabine + nab-paclitaxel by clinician choice, then reassessment for surgery. Resected pts received 3 more months adjuvant; unresected pts 3 more months systemic chemo.
SBRT 40 Gy in 5 fractions with fiducial marker guidance and real-time RT quality assurance. 39 of 49 (80%) assigned to SBRT initiated it.
Primary: locoregional recurrence at 12 months. Secondary: PFS, OS, surgical outcomes, toxicity.
Primary endpoint met; benefit significant in the potentially operable stratum, not significant in inoperable disease (P=0.16). Resection and R0 rates numerically higher with SBRT, both non-significant.
| Endpoint | Chemo + SBRT | Chemo alone | P |
|---|---|---|---|
| 12-mo LRR, all | 20.2% | 52.0% | 0.022 |
| 12-mo LRR, POPC | 19.7% | 52.9% | 0.031 |
| 12-mo LRR, IPC | 21.4% | 50.0% | 0.16 |
| mPFS | 11.9 mo | 6.3 mo | 0.002 |
| mOS | 22.0 mo | 14.0 mo | 0.006 |
| Resection (POPC) | 21/31 (68%) | 10/17 (59%) | 0.54 |
| R0 (>1 mm), resected | 62% | 40% | 0.44 |
| G3+ toxicity | 70.2% | 64.0% | 0.27 |
G3+ toxicity 70.2% vs 64.0% (P=0.27), no significant increase with SBRT. RT-specific and late toxicity not broken out in source.
Randomized evidence for adding RT to chemo in pancreatic cancer has been inconsistent: LAP07 tested conventional chemoRT in locally advanced disease, and PREOPANC tested preoperative chemoRT in resectable and borderline disease. MASTERPLAN differs by pairing short-course SBRT with modern multiagent chemo and by powering on local control rather than OS.
Incomplete SBRT uptake (80%) and clinician-chosen chemo add noise to a small trial. The OS gain sits on a secondary endpoint with no HR reported in the source, and late GI toxicity is not described.
A local control benefit of this size, carried into PFS and OS, makes a larger confirmatory trial a priority. It does not yet settle which stratum benefits, whether the OS signal is real, or how SBRT should be sequenced with surgery.
Randomized with primary endpoint met, but N=74 across heterogeneous strata, 80% SBRT uptake, and OS/PFS secondary; phase not stated, conference trade-press source only.
- Does the OS benefit hold in a larger randomized trial? recruiting Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2n=256 · primary completion 2027-12 · preop chemo ± isotoxic high-dose SBRT in BRPC, n=256not yet Locally Advanced Pancreatic Cancer Treated With ABLAtivE Stereotactic MRI-guided Adaptive Radiation Therapy Phase NAn=267 · primary completion 2028-08 · 2:1 RCT, ablative MR-guided SBRT vs chemo alone, n=267
- Does SBRT benefit locally advanced/inoperable disease specifically? active mFOLFIRINOX With or Without Stereotactic Body Radiotherapy in Locally Advanced Pancreatic Adenocarcinoma Phase 2n=92 · primary completion 2025-01 · mFOLFIRINOX ± SBRT in unresectable LAPCnot yet Locally Advanced Pancreatic Cancer Treated With ABLAtivE Stereotactic MRI-guided Adaptive Radiation Therapy Phase NAn=267 · primary completion 2028-08 · LAPC post-induction chemo: ablative SMART vs chemo alone
- Late duodenal/gastric toxicity of 40 Gy/5fx with modern chemo
📚 Sources · 📄 1 paper
Abstract
2026-10-31 ESMO Congress 2026
KEYNOTE-975 NCT04210115
ForUntreated unresectable locally advanced ESCC/EAC/GEJ, dCRT candidates
HR 0.97
95% CI 0.77-1.23, P=0.3994; not met (boundary 0.0193)
TL;DREFS HR 0.97 (95% CI 0.77-1.23), median 15.2 vs 14.7 mo in PD-L1 CPS ≥10: no EFS gain adding concurrent pembro to dCRT in unresectable esophageal/GEJ cancer.
The trial failed in the enriched PD-L1 CPS ≥10 group, where IO was most likely to help, and the curves sat on top of each other (EFS HR 0.97, OS HR 1.00) at 47.1 mo median f/u. Grade 5 AEs ran 13% vs 10%, so concurrent pembro with 50-60 Gy dCRT adds toxicity without benefit. This leaves dCRT alone as the backbone.
In untreated unresectable esophageal or GEJ cancer going to dCRT, including PD-L1 CPS ≥10, this does not support concurrent pembrolizumab; it does not address consolidation-only IO after dCRT or the resectable trimodality setting. The longer read
Concurrent pembro with 50-60 Gy dCRT did not move EFS (HR 0.97) or OS (HR 1.00) in CPS ≥10 pts, and grade 5 AEs rose to 13% vs 10%. No local control or dose-stratified data in source, so the RT backbone stays dCRT alone with no IO-driven change to dose or volume.
PD-L1 CPS ≥10 enrichment did not rescue concurrent pembro (EFS HR 0.97, OS HR 1.00), and AE discontinuation rose to 34% vs 27%. Biomarker selection does not justify adding PD-1 blockade to dCRT; consolidation-only timing remains untested by this trial.
9 details
International phase 3, randomized 1:1, double-blind, placebo-controlled, multicenter; N=703. Results are from the second interim analysis (IA2), after which the study was stopped. Median follow-up 47.1 mo.
Previously untreated locally advanced unresectable ESCC, EAC or GEJ cancer (cTX N+ M0 or cT2-T4a NX M0), or cervical/upper thoracic EC with supraclavicular nodal M1 only. ECOG 0-1, ineligible for curative surgery but suitable for dCRT.
Pembro 200 mg or placebo Q3W for 8 cycles, then 400 mg or placebo Q6W for 5 cycles, concurrent with dCRT. Chemo backbone FP or FOLFOX by site choice.
50 Gy or 60 Gy with FP, or 50 Gy with FOLFOX, by site choice. Fractionation, technique and target volume not reported in source.
Dual primary: investigator-assessed EFS and OS, tested hierarchically in PD-L1 CPS ≥10, CPS ≥1, then all pts.
EFS not improved in CPS ≥10 (arm-level numbers in table), so every downstream comparison went untested and the study was stopped.
| Endpoint (CPS ≥10) | Pembro + dCRT | Pbo + dCRT | HR (95% CI), P |
|---|---|---|---|
| Median EFS (investigator) | 15.2 mo | 14.7 mo | 0.97 (0.77-1.23), P=0.3994; boundary 0.0193 |
| Median OS | 32.2 mo | 35.0 mo | 1.00 (0.77-1.30), nominal P=0.5003 |
| AE | Pembro + dCRT | Pbo + dCRT |
|---|---|---|
| Grade ≥3 | 100% | 100% |
| Grade 5 | 44 (13%) | 37 (10%) |
| Discontinuation for any AE | 117 (34%) | 97 (27%) |
Grade ≥3 AEs in 100% of both arms. Grade 5 AEs 44 (13%) vs 37 (10%), AE discontinuation 117 (34%) vs 97 (27%). Authors report no new safety signals.
Joins KUNLUN (durvalumab + dCRT) as a negative concurrent IO-dCRT trial in esophageal cancer. Adjuvant nivolumab per CheckMate 577 belongs to the resected trimodality setting and is untouched by this result.
RT dose and chemo backbone by site choice with no outcome breakdown, pooled histologies, and no local control or failure-pattern data in source to show whether IO changed in-field control.
A flat EFS and OS in the PD-L1-enriched group argues against a hidden benefit in the untested CPS ≥1 or all-comer groups. Whether timing (consolidation vs concurrent) or histology matters stays open.
CONSORT flow
Double-blind phase 3 stopped at IA2 after the gatekeeper EFS endpoint failed in the enriched CPS ≥10 group; reaffirms dCRT alone as standard. Downstream populations formally untested.
- Would consolidation-only IO after dCRT differ from concurrent dosing?
- Histology-specific EFS in ESCC vs EAC/GEJ
- Did pembro alter local control or failure patterns?
📚 Sources · 📄 1 paper
Abstract
2026-10-04 ASTRO Annual Meeting 2026
SOFT Preop
ForResectable, borderline or LA type A PDAC, ECOG 0-2, post >1 mo neoadj chemo
41% vs 38%
SBRT vs Chemo-RT, p = 0.754, ns; chemo-RT superiority hypothesis not met
TL;DRPath node positivity 41% SBRT vs 38% chemo-RT (p = 0.754) preop in PDAC; mOS 26.04 vs 42.96 mo (p= 0.639); QOL favored SBRT.
Local/regional recurrence split 6 SBRT vs 2 chemo-RT (8 events, 7.8%) at median follow-up 3.4 years, with elective nodes at 25 Gy/5 and primary at 33-40 Gy in 5, mostly on 1.5 T adaptive MR guidance. The preop fractionation choice moves toward SBRT on QOL only where that nodal volume and platform are reproduced.
In resectable, borderline, or LA type A PDAC already through >1 month of neoadjuvant chemo and planned for preop RT, this informs choosing 5-fraction SBRT over 28-fraction chemo-RT on QOL grounds; it does not address whether preop RT adds to chemo alone. The longer read
Local/regional recurrence split 6 SBRT vs 2 chemo-RT (8 events, 7.8%) at median follow-up 3.4 years, with elective nodes at 25 Gy/5 and primary at 33-40 Gy in 5, mostly on 1.5 T adaptive MR guidance. The fractionation choice moves toward SBRT on QOL only where that nodal volume and platform are reproduced.
83/98 (84.7%) reached resection, 41 SBRT and 42 chemo-RT, with no difference in surgical complications, so the 5-fraction course did not cost operability. Node positivity was 41% vs 38%; margin negativity and pathologic response are called equal but no figures appear in the abstract.
11 details 1 trial watching
Prospective, randomized phase II, 1:1 allocation after neoadjuvant chemo. 102 pts targeted and enrolled, anticipating a 15% drop out before surgery; 4 withdrew after enrollment. Median follow-up among all enrolled pts 3.4 [2.6, 5.1] years.
Resectable, borderline, or locally advanced (LA) type A PDAC, ECOG 0-2, > 1 month of neoadjuvant chemo. Median age 65 (34-82); 38%/42%/20% resectable, borderline, and LA type A. Prior chemo was FOLFIRINOX (79%), gemcitabine/nab-paclitaxel (12%), or other (9%), with 92% receiving more than 2 months.
Chemo-RT: 50.4 Gy/28 fractions with weekly gemcitabine or capecitabine. SBRT: 25 Gy/5 to elective nodes and 33-40 Gy in 5 to the primary, without concurrent chemo. Most SBRT pts were treated using 1.5 T adaptive MRI guidance.
Primary: pathologic node positivity, hypothesizing lower rates with chemo-RT. Secondary: PFS, OS, patient-reported QOL (PROMIS), physician-reported toxicity, surgical complications, translational endpoints.
Arm-level figures are in the table. 83/98 (84.7%) completed all intended therapy including surgical resection, equal in both arms.
| Endpoint | SBRT | Chemo-RT | p |
|---|---|---|---|
| Path node positivity | 41% | 38% | p = 0.754 |
| Median OS | 26.04 mo (95% CI 17.9 to 59.28) | 42.96 mo (95% CI 18.72 to 54.72) | p= 0.639 |
| Alive at 3 years | 42.6% | 57.5% | p = 0.198 |
| PFS | 14.28 mo (95% CI 9-29.64) | 21.6 mo (95% CI 10.56-38.04) | p = 0.96 |
| Local/regional recurrence (events) | 6 | 2 | not reported |
| Completed all therapy incl. resection | 41 | 42 | not reported |
No difference in surgical complications; no rates given. Physician-reported toxicity was a secondary endpoint but is not reported in the abstract. PROMIS physical function, global physical health, and fatigue were better preserved with SBRT (p = < 0.05).
Alliance A021501 tested preop SBRT or hypofractionated RT against chemotherapy alone, and PREOPANC established gemcitabine-based preop chemo-RT against upfront surgery. Neither compared one RT schedule with another. The authors describe this as the first randomized trial comparing SBRT with chemo-RT in the neoadjuvant setting for PDAC.
Abstract only: no per-arm allocation counts, no QOL magnitudes or timepoints, and no figures for pathologic response or margin negativity despite the conclusion citing them. QOL is patient-reported in an unblinded comparison. Concurrent agent varied in the chemo-RT arm and primary SBRT dose ranged 33-40 Gy.
The trial shows SBRT is deliverable preop with equal resection completion and better QOL, and it does not show nodal sterilization differs. It does not settle survival equivalence: median OS 26.04 vs 42.96 mo and LRR 6 vs 2 point the same direction in a sample too small to resolve them.
Randomised phase II, N=102, built to show chemo-RT superiority on nodal positivity and null. Not an equivalence design; survival and LRR lean numerically toward chemo-RT.
- Is preop SBRT non-inferior to chemo-RT for OS in PDAC?
- Does 25 Gy/5 elective nodal SBRT give adequate regional control?
- Does any preop RT add to neoadjuvant FOLFIRINOX alone? recruiting Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2n=256 · primary completion 2027-12 · preop mFOLFIRINOX +/- isotoxic high-dose SBRT in BRPC
📚 Sources · 📄 1 paper
Abstract
2026-06-10
RTOG 0848 NCT01013649
ForResected pancreatic head adenocarcinoma, post 6 cycles adjuvant gemcitabine-based chemo
HR 0.96
90% CI 0.79-1.18, 1-sided P=.38; did not meet OS
TL;DRAdjuvant CXRT after 6 cycles gemcitabine-based chemo missed OS (HR 0.96), but node-negative pts gained: 5yr OS 48.1% vs 28.6%.
The whole RT read sits in 91 node-negative pts: 5yr OS 48.1% vs 28.6%, median OS 3.9 vs 3.0 yr, with interaction P=.022. Delivery was standard and QA'd (50.4 Gy/28 fx, tumor bed plus pancreatojejunostomy plus regional nodes, 81% IMRT), so the technique transfers directly. G4-5 toxicity was unchanged (6% v 5%).
In a resected pancreatic head adenocarcinoma pt who is node-negative and progression-free after adjuvant chemotherapy, this supports discussing CXRT; it does not extend to node-positive disease, where no treatment effect was seen, or to margin-positive pts (only 10 node-negative/margin-positive across both arms). The longer read
The RT signal is confined to 91 node-negative pts: 5yr OS 48.1% vs 28.6%, median OS 3.9 vs 3.0 yr, interaction P=.022. Technique transfers unchanged (50.4 Gy/28 fx, tumor bed plus pancreatojejunostomy plus regional nodes, 81% IMRT, real-time central review), and G4-5 toxicity was flat at 6% v 5%.
The systemic backbone dates the result: 67% got single-agent gemcitabine, 28% gemcitabine plus erlotinib, and no pt received FOLFIRINOX. Unselected CXRT after six cycles adds nothing (OS HR 0.96), so referral for adjuvant RT stays off the default path, though the grade 3 excess (38% v 19%) is GI and lymphopenic, not prohibitive.
10 details 2 trials watching
Prospective randomized phase IIR/III, two-step, multicenter (RTOG then NRG). Step 2 opened November 2009, closed October 2018, analyzed December 2023. Randomization 1:1, unmasked, stratified by nodal status, CA19-9, margins and adjuvant systemic treatment.
Curative-intent gross total resection of pancreatic head adenocarcinoma with documented microscopic margin status; body/tail excluded. Only pts without recurrence after five cycles of chemotherapy entered step 2: 546 entered step 1, 354 randomized (174 chemo, 180 chemo+CXRT). 74% node-positive, 17% margin-positive, 81% T3.
Step 1 was gemcitabine (67%), gemcitabine plus erlotinib (28%) or non-oxaliplatin gemcitabine combinations (5%); no pt received FOLFIRINOX. Both arms then took a sixth cycle; the experimental arm followed with CXRT within 21 days, sensitized by capecitabine (83%) or infusional 5-FU (15%).
50.4 Gy in 28 fractions to the postoperative tumor bed, pancreatojejunostomy and regional nodes; median delivered dose 50.4 Gy over 28 fractions and 38 days. 81% IMRT, 19% 3D conformal, 79% with no interruptions, 88% received ≥50 Gy. Centers were IROC-credentialed and every plan underwent real-time central review before start.
Primary: overall survival from second-step randomization. Secondary: DFS and adverse events (CTCAE v4.0). Final analysis triggered at the earlier of 316 OS events or 5 years of potential follow-up for all pts; it fired on the latter with 270 events, cutting power to 72%.
Grade 4 or 5 AEs were not increased (6% v 5%, P=.68), with one grade 5 in each arm (hepatic failure, sepsis). Grade 3 rose to 38% v 19% (P<.001), driven by GI events and decreased lymphocyte count; grade 3 nonhematologic 22% v 11% (P=.004).
ESPAC-1 reported adjuvant CXRT as detrimental, but accrued 1994-2000 with split-course lower-dose 2D planning, no postoperative imaging to exclude incomplete resection or early metastases, and no QA. RTOG 9704's post hoc analysis linked RT protocol deviations to worse survival, the specific failure mode 0848 designed its real-time review to prevent.
Accrual took almost 9 years and the OS event rate ran below projection, so the trial read out on a follow-up trigger at 270 of 316 planned events (power 72% for the hypothesized HR 0.76). The node-negative arms hold 42 and 49 pts, and the subgroup rests on an interaction P=.022 across nine tested subgroups.
The negative primary settles that unselected adjuvant CXRT adds nothing after gemcitabine-based chemotherapy, while the safety profile removes the ESPAC-1-era objection that RT here is harmful. What stays open is whether the node-negative signal reflects a real locoregional benefit in pts with lower competing distant risk, and whether it survives a modern FOLFIRINOX backbone.
| Endpoint | Chemo (n=42) | Chemo+CXRT (n=49) |
|---|---|---|
| 5yr OS (95% CI) | 28.6 (14.9-42.2) | 48.1 (33.3-62.9) |
| Median OS, yr (95% CI) | 3.0 (2.2-4.0) | 3.9 (2.5-NR) |
| Median DFS, yr (95% CI) | 1.5 (0.8-2.7) | 2.3 (1.4-NR) |
CONSORT flow
Prespecified stratified phase III, primary OS endpoint negative overall. Node-negative benefit rests on a subgroup interaction (P=.022) in 91 pts, hypothesis-generating not definitive.
- Does the node-negative CXRT benefit hold on a FOLFIRINOX backbone?
- Can SBRT substitute for conventional CXRT in this setting? active mFOLFIRINOX With or Without Stereotactic Body Radiotherapy in Locally Advanced Pancreatic Adenocarcinoma Phase 2n=92 · primary completion 2025-01 · candidate match
- How to select for RT benefit when nodal status follows neoadjuvant therapy? active Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma Phase 2n=39 · primary completion 2022-02 · candidate match
📚 Sources · 📄 1 paper
2026-05-31
RASolute 302
ForPreviously treated metastatic pancreatic cancer, RAS G12-mutant
TL;DRMedian OS 13.2 vs 6.6 mo, HR 0.40 (95% CI 0.30-0.54), P<0.001, daraxonrasib over chemo in previously treated RAS G12 metastatic pancreatic cancer.
In previously treated metastatic pancreatic cancer with a RAS G12 mutation, this supports daraxonrasib over investigator's choice chemotherapy on OS; it does not extend to treatment-naive or non-metastatic disease.
| Population | Arm | N | Events, n (%) | mOS, mo (95% CI) | HR for death (95% CI) |
|---|---|---|---|---|---|
| RAS G12 | Daraxonrasib | 228 | 72 (32) | 13.2 (10.0-NR) | 0.40 (0.30-0.54), P<0.001 |
| RAS G12 | Chemotherapy | 231 | 127 (55) | 6.6 (5.4-8.2) | ref |
| Overall | Daraxonrasib | 248 | 79 (32) | 13.2 (10.0-NR) | 0.40 (0.30-0.53), P<0.001 |
| Overall | Chemotherapy | 252 | 141 (56) | 6.7 (5.8-8.0) | ref |
8 details 2 trials watching
Phase, randomization and primary endpoint not stated in source. HRs came from a stratified Cox model and P values from a stratified log-rank test. Presented at ASCO as abstract LBA5.
Previously treated metastatic pancreatic cancer. OS reported in a RAS G12 population (228 vs 231) and an overall population that also includes G13 or Q61 mutations or no RAS mutation identified (248 vs 252).
Daraxonrasib vs investigator's choice chemotherapy. Dose, schedule and the chemo options allowed are not stated in source.
OS favored daraxonrasib in both populations with HR 0.40, P<0.001; per-arm values are in the figure table.
Second-line metastatic pancreatic cancer has been a chemotherapy space, with NAPOLI-1 establishing a nal-IRI based option. An OS benefit for a RAS-directed agent over chemo is a different class of result; no cross-trial numbers are reported in source.
Safety and follow-up duration not reported in source; the daraxonrasib median OS upper CI is not reached. Composition of the investigator's-choice control is unknown, which bears on comparator strength.
The identical HR 0.40 in both populations reflects that the overall population is almost entirely RAS G12, not a demonstrated benefit beyond G12. Events of 32% vs 55% and 56% mean the daraxonrasib median of 13.2 mo rests on fewer events and may move with maturity.
OS HR 0.40 vs investigator's-choice chemo, P<0.001, consistent in RAS G12 and overall populations; source frames it as historic. Tweet omits phase and design.
- Benefit in RAS G13, Q61, or no-RAS-mutation tumors?
- Durability of OS benefit with longer follow-up
- Role in first-line metastatic pancreatic cancer recruiting Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Phase 3n=900 · primary completion 2028-06 · phase 3 daraxonrasib ± GnP vs chemo, 1L metastatic PDACn=400 · primary completion 2029-03 · phase 3 zoldonrasib + daraxonrasib vs GnP, 1L KRAS G12D
📚 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
2026-05-30 ASCO Annual Meeting 2026
Neo-CRAG
ForcT3N2-3M0 / cT4 gastric or Siewert II-III EGJ adenocarcinoma, D2-resectable
HR 0.750
95% CI 0.607-0.928, P=0.008; 3yr DFS 55.6% vs 42.4%
TL;DRAdding preop 45Gy/25fx to periop XELOX raised 3yr DFS 55.6% vs 42.4%, HR 0.750; mOS 67.5 vs 37.6mo.
The RT case here rests on locoregional control: LRR after R0 fell to 9.4% from 18.3%, tracking the ypN0 (56.1% vs 36.4%) and pCR gains, which is the mechanistic chain CRITICS and TOPGEAR never produced. Dose was conventional 45Gy/25fx preoperatively, and G3+ postop complications stayed flat (9.0% vs 7.6%), so the deliverability objection to preop RT before D2 loses force.
In node-heavy cT3N2+ or cT4 gastric/Siewert II-III disease heading to D2 resection, this supports revisiting preoperative chemoRT rather than chemo alone; it does not speak to cT2N0-N1 disease or to pts already committed to a FLOT backbone. The longer read
Conventional 45Gy/25fx delivered preoperatively, after cycle 1 of chemo, halved locoregional recurrence after R0 resection (9.4% vs 18.3%) with no excess G3+ postoperative complications (9.0% vs 7.6%). That combination, a local-control gain without a surgical-morbidity cost, is what the omission decision in node-heavy cT3N2+ disease has been waiting for.
The systemic backbone was XELOX in both arms, so the DFS gain is attributable to radiotherapy rather than to the regimen, but the control arm's 37.6 mo median OS is the caveat: this does not tell you whether radiotherapy still adds on top of FLOT, whose own advantage is partly locoregional. Sequencing of RT after cycle 1 with attenuated dosing was deliverable.
Every pt was intended for standardized D2 resection, and preoperative chemoRT did not degrade it: G3+ postoperative complications were 9.0% vs 7.6%, and 448 of 620 randomised pts reached gastrectomy. ypN0 rose to 56.1% from 36.4%, which changes what the surgeon can expect to find in the nodal basin rather than the extent of dissection required.
| Endpoint | CRT | CT | Effect size |
|---|---|---|---|
| 3yr DFS | 55.6% (50.1-61.1) | 42.4% (36.9-47.9) | HR 0.750 (0.607-0.928), P=0.008 |
| Median DFS | 52.7 mo | 24.4 mo | n/a |
| 5yr OS | 50.1% | 44.2% | HR 0.781 (0.628-0.970), P=0.025 |
| Median OS | 67.5 mo | 37.6 mo | n/a |
9 details
Randomised, multicenter, phase 3 trial, N=620 (310 per group), 13 referral hospitals in China, accrual 2013-2022. Follow-up on the DFS curve extends past 120 months.
High-risk locally advanced gastric or EGJ adenocarcinoma: cT3N2-3M0, cT4aN+M0, or cT4bNanyM0, Siewert II/III permitted. 225 (36.3%) had an EGJ primary, and every pt was intended for standardized D2 resection.
Both arms: 3 cycles preoperative XELOX (oxaliplatin 130 mg/m² D1, capecitabine 1000 mg/m² BID D1-14, Q3W) then D2 gastrectomy then 3 adjuvant XELOX cycles.
CRT arm added concurrent 45 Gy / 25 fractions after cycle 1 of preoperative chemo, with attenuated concurrent dosing (oxaliplatin 100 mg/m², capecitabine 825 mg/m²). Target volume not specified in source.
Primary: disease-free survival, from randomization to progression, relapse, or death. Secondary: overall survival, pCR, R0 resection, safety.
Primary endpoint met. The locoregional read is the one an RT reader needs: LRR 9.4% vs 18.3% among R0-resected pts.
G3+ haematologic toxicity 14.6% vs 10.3%, the expected cost of concurrent chemoRT. G3+ postoperative complications were comparable, 9.0% vs 7.6%, so preoperative RT did not measurably worsen D2 surgical morbidity.
CRITICS (postoperative chemoRT after D1+ surgery) and TOPGEAR (preoperative chemoRT with ECF/FLOT) both failed to show a survival gain for radiotherapy in this disease. Neo-CRAG differs on three axes at once: RT given preoperatively, D2 resection mandated, and enrolment restricted to node-heavy cT3N2+ or cT4 disease.
The 2013-2022 accrual window means the control arm reflects a doublet era; a 37.6 mo median OS in the control group is short against contemporary FLOT-treated series. Single-country enrolment with uniformly high-quality D2 surgery also caps generalisability to centres with variable nodal dissection.
The pCR, downstaging, ypN0 and LRR gradient forms a coherent mechanistic chain from RT to the DFS separation, which is what earlier negative trials lacked. What it does not settle is whether that chain survives a stronger systemic backbone, since much of FLOT's advantage over a doublet is itself locoregional.
CONSORT flow
Randomised ph3, prespecified DFS met with OS support, but the chemo backbone is XELOX not FLOT, so it contests RT omission without settling it.
- Does preoperative chemoRT still add benefit on a FLOT backbone?
- Generalizability outside high-volume D2 centers
- Optimal target volume and elective nodal coverage not reported in source
📚 Sources · 🐦 1 tweet
Neo-CRAG: Ph3 RCT (n=620, gastric/GEJ) - adding neoadj chemoRT to peri-op XELOX improved OS (68 v 38 mo).
— Dr. Nina Niu Sanford (@NiuSanford) May 30, 2026
Limitation=non-FLOT, BUT still relevant IMO b/c:
1) DFS/OS benefit substantial.
2) Improvements in pCR, downstg, LRR supports plausible RT effect on OS. #ASCO26 @OncoAlert pic.twitter.com/eeM0Z8p20M