SPECIAL ASCO '26 EDITIONISSUE 02 · 3 JUNE 2026
ASCO 2026 PLENARY · DARAXONRASIB DOUBLES OS IN PANCREATIC CANCER · 13.2 vs 6.7 MONTHS · PROTEUS: PERIOP APALUTAMIDE CUTS METASTASIS RISK 20% · CROWN 7-YEAR: MEDIAN PFS STILL NOT REACHED |
ASCO 2026 PLENARY · DARAXONRASIB DOUBLES OS IN PANCREATIC CANCER · 13.2 vs 6.7 MONTHS · PROTEUS: PERIOP APALUTAMIDE CUTS METASTASIS RISK 20% · CROWN 7-YEAR: MEDIAN PFS STILL NOT REACHED |
PLENARY · PANCREATIC · NEJM
A pill just doubled survival in pancreatic cancer.
RASolute 302. Daraxonrasib, an oral RAS(ON) inhibitor, in previously treated metastatic PDAC. The first targeted agent to move overall survival in a disease that almost never moves.
Dr. Signal's verdict
Change Practice
13.2 mo
median OS vs 6.7 mo chemo
8.5 mo
median follow-up, still maturing
60%
lower risk of death (HR 0.40)
THE SOURCE
READ THE FULL PAPER →
"They gave it a standing ovation. We gave it a verdict."
ASCO PLENARY · NEJM
P.02
Signal vs Noise
+ guess the trial
P.03
Trials This Week
15 verdicts, all linked
P.04
Case of the Week
+ 100 Words
P.05-06
The ASCO Recap
+ hot take & radar
THIS WEEK'S SIGNALS
ISSUE 02 · 3 JUNE 2026
“
ASCO 2026 gave us one genuine revolution, one quiet reinforcement, and a dozen results that need another year. Here is what to act on Monday, and what to let mature.
SIGNALact on it
RASolute 302 - daraxonrasib doubled OS in pretreated mPDAC (13.2 vs 6.7 mo). Expanded access is open; identify eligible patients now.
LIBRETTO-432 - adjuvant selpercatinib cut recurrence or death 83% in early-stage RET+ NSCLC. Test RET at diagnosis, not just in advanced disease.
SARC041 - abemaciclib improved PFS to 9.7 vs 1.5 months (HR 0.38) in advanced dedifferentiated liposarcoma. A first targeted option where there were almost none.
NOISEwait before acting
persevERA - giredestrant + palbociclib missed the primary PFS endpoint vs letrozole + palbociclib in 1L ER+/HER2- mBC. A numerical edge is not a win. Oral SERDs are not ready for the first line.
NHS-Galleri - the multicancer blood test missed its primary endpoint (fewer stage III/IV cancers overall). The stage IV signal is intriguing, but mortality, specificity, and cost-effectiveness all need more data.
EMERALD-3 - STRIDE + TACE + lenvatinib met its PFS endpoint in unresectable HCC, but the lenvatinib-free arm looked just as good. Lenvatinib's added role is doubtful, and OS is awaited.
Noise section contributed by Dr Narendhar Gokulanathan · @foxpaws_onco
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ONCOSIGNALS WEEKLY
ASCO 2026 · CHICAGO · ISSUE 02
Trials This Week
DR. SIGNAL'S VERDICT ON EVERY RESULT · ALL TRIAL NAMES LINKED TO SOURCE
Breast2 RESULTS
0.67 HR
Carboplatin (AUC 5 x4, with the taxane) added to AC then taxane, (neo)adjuvant. 868 patients, stage II-III triple-negative breast cancer.
82.3% +carboplatin vs 75.1% control
"A clean EFS win, and the cleanest answer yet to the platinum question in TNBC. But every secondary only trended (OS, IDFS, DRFS, pCR all NS) and grade 3+ adverse events rose to 74.7% (from 56.7%). This is the platinum question, not the KEYNOTE-522 immunotherapy one."
82.5%
Final 15-year outcomes, premenopausal HR-positive early breast cancer. Exemestane + OFS vs tamoxifen + OFS vs tamoxifen alone.
vs 68.1% OS, age <35 HER2-
"Adding ovarian suppression keeps cutting recurrence, but 15-year survival across the trial is flat (85 to 87%). The real gains are in the young and high-grade: under 35 with HER2-negative disease, 15-yr OS was 82.5% vs 68.1%. Intensify by risk, not by reflex."
Genitourinary2 RESULTS
20%
Perioperative apalutamide + ADT around prostatectomy. High-risk localized prostate, n=2,109. 5-yr MFS 78.2% vs 73.5%.
"Both endpoints met, next therapy delayed past six years. But apalutamide isn't approved here, OS is flat so far (HR 1.08), and pCR stays modest. Flag your high-risk patients; don't change the consent form yet."
Gastrointestinal3 RESULTS
13.2 mo
Median OS with daraxonrasib vs 6.7 months chemotherapy. HR 0.40, 60% lower risk of death, p<0.0001.
vs 6.7 mo chemo
Oral RAS(ON) inhibitor. Pretreated metastatic PDAC, ~500 randomized. ORR roughly tripled.
"The first targeted agent to move survival in pretreated pancreatic cancer. Follow-up is short at 8.5 months, so the number may still shift. Real, and worth acting on the moment you can access it."
15.2 mo
Encorafenib + cetuximab + FOLFIRI vs FOLFIRI +/- bevacizumab, 1L BRAF V600E metastatic colorectal, n=147. ORR 64.4% vs 39.2%.
vs 8.3 mo chemo
"Targeted beats chemo across ORR, PFS and OS, now on an irinotecan backbone for oxaliplatin-wary patients. Small, with the OS interval still wide. Confirms targeted-first, not which doublet wins."
52%
ctDNA-guided adjuvant chemo vs observation, resected stage II MSS colon. 1,722 screened, 55 ctDNA-positive; closed early.
3-yr DFS 52% ctDNA+ vs 87% ctDNA-
"ctDNA is powerfully prognostic (3-yr DFS 52% vs 87%). On treatment the ITT endpoint was negative, but only because early closure gutted the power; per-protocol showed real benefit (HR 0.31). Negative on paper, supportive in practice."
Lung5 RESULTS
83%
Adjuvant selpercatinib vs placebo, resected stage IB-IIIA RET fusion-positive NSCLC, n=151. 24-mo EFS 92% vs 61%.
"The ADAURA moment for RET, one of the largest adjuvant effects in lung cancer. Small, OS immature, real transaminitis. The change is upstream: test RET at diagnosis, not just in advanced disease."
0.65 HR
First-line sunvozertinib vs platinum chemo, EGFR exon20ins NSCLC, n=324. PFS favored sunvozertinib.
PFS vs platinum chemo
"A first-line oral option for a subgroup that had none. Open-label with crossover, so OS will be murky. Confirm the insertion on NGS first."
27.9 mo
Ivonescimab (PD-1/VEGF bispecific) + chemo vs tislelizumab + chemo, 1L squamous NSCLC, n=532. HR 0.66.
vs 23.7 mo tislelizumab + chemo
"A real win head-to-head against an active PD-1, not placebo. But entirely China-based and unapproved elsewhere. Watch the global trials before extrapolating."
65%
Sac-TMT (TROP2 ADC) + pembrolizumab vs pembrolizumab, 1L PD-L1-positive NSCLC, n=413.
HR 0.35 vs pembrolizumab alone
"A big PFS effect and an appealing chemo-free first line. But interim, open-label, China-only, PFS not OS. Watch closely, don't switch."
0.19 HR
First-line lorlatinib vs crizotinib, advanced ALK-positive NSCLC, n=296. 7-yr PFS 55% vs 3%.
5-yr PFS 60% vs 8% crizotinib
"Seven years in, first-line lorlatinib still hasn't reached median PFS (vs 9.1 mo), with no new brain progression after month 30. Post-hoc, OS immature, and the comparator is crizotinib, not a modern ALK TKI. Nothing changes Monday, and that's the point."
Hematology2 RESULTS
25%
Tafasitamab + lenalidomide + R-CHOP vs R-CHOP, 1L high-risk DLBCL. Global, placebo-controlled. PFS improved.
lower progression or death vs R-CHOP
"R-CHOP has resisted improvement for 20 years, so a first-line PFS win matters. Added toxicity and cost, OS immature. A backbone to prepare for, pending the curves and label."
71%
Teclistamab monotherapy vs PVd/Kd, relapsed/refractory myeloma, 1-3 prior lines, n=593. 18-mo PFS 69.8% vs 26.9%; OS HR 0.60.
mPFS not reached vs 8.2 mo
"A chemo-free, off-the-shelf bispecific beating active triplets at first relapse. CRS and infection demand the right setting. A 71% PFS reduction this early is hard to argue with."
Sarcoma1 RESULT
9.7 mo
Abemaciclib vs placebo, advanced dedifferentiated liposarcoma, n=108. 6-mo PFS 60% vs 22%. CDK4 amplified in nearly all DDLPS.
"The first positive phase 3 ever in dedifferentiated liposarcoma. Crossover, PFS not OS, responses still uncommon. A real option where there were none."
CLINICAL VIGNETTE & 100 WORDS
ISSUE 02 · 3 JUNE 2026
Test Yourself
Case of the Week
A 59-year-old never-smoker has a fully resected 5 cm, node-positive (stage IIIA) lung adenocarcinoma and recovers well (ECOG 0). She completes adjuvant cisplatin-based chemotherapy. Molecular testing returns a RET fusion. What do you offer next?
SELECT ONE
A
Surveillance imaging alone
B
Adjuvant osimertinib
C
Adjuvant selpercatinib
D
Adjuvant durvalumab
C - Adjuvant selpercatinib
LIBRETTO-432 cut recurrence or death by 83% (HR 0.172) with adjuvant selpercatinib in resected stage IB-IIIA RET fusion-positive NSCLC, putting RET alongside EGFR (ADAURA) and ALK (ALINA) as a curative-setting target. Osimertinib hits the wrong driver, durvalumab is not driver-directed, and observation now leaves benefit on the table. The real lesson is upstream: this option only exists if you test RET in early-stage disease. Run broad molecular testing on every resected NSCLC, not just advanced.
-
A
-
B
-
C
-
D
Answer first, then read the evidence. The reveal shows what the trial data actually support - not what felt right.
100 WORDS · ONE COLUMN, ONE HUNDRED WORDS
100Words
This week: forty years later, the undruggable got drugged.
For forty years, RAS was the wall. Every oncologist learned the same hard lesson: the most common driver in the deadliest cancers was the one we could not touch. We told patients the truth, and we hated it. Then, in Chicago, the wall came down. Daraxonrasib drugged the undruggable, and people with pancreatic cancer, of all cancers, lived longer. The numbers will mature and the arguments will follow, as they should. But for one afternoon the room stood up, because every clinician in it had waited a whole career for this. The impossible target is a target now. Hold on to that.
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ASCO 2026 · THE RECAP
ISSUE 02 · 3 JUNE 2026
ASCO 2026
The Recap
The Recap
EHA
11-14 JUN 2026
DR. SIGNAL'S PICKDaraxonrasib, above everything. A pill moved survival in pancreatic cancer. We do not say that sentence often.
Breast
Switching to camizestrant on emergent ESR1m ctDNA, before progression, lifted PFS to 16 vs 9.2 mo (HR 0.44). FDA ODAC voted 6-3 against a favorable benefit-risk.
ctDNA SWITCHA genomic assay let two-thirds of high-risk ER+ patients skip chemo, non-inferior (HR 0.99). Biology over anatomy.
DE-ESCALATIONPerioperative pembrolizumab held its survival edge at 7.8 yr: 7-yr OS 85.1% vs 77.2% (HR 0.64). SOC for high-risk early TNBC.
MATURE SOCAdjuvant giredestrant beat standard endocrine therapy (3-yr IDFS HR 0.65 pre, 0.74 post). First adjuvant win for an oral SERD.
ORAL SERDEGFR x HER3 bispecific ADC hit dual PFS + OS in post-taxane TNBC. A new drug class; China interim data.
BISPECIFIC ADCOmitting completion axillary dissection for 1-2 positive sentinel nodes was safe (5-yr OS 94.4% vs 93.4%). Less surgery, same survival.
LESS SURGERYGenitourinary
Perioperative apalutamide cut metastasis-or-death 20% in high-risk localized prostate. Investigational here; OS flat so far.
PLENARYAt 42 months, 83.6% of complete responders still alive. Confirms enfortumab vedotin + pembro as 1L urothelial standard.
MATURE SOCGastrointestinal
Encorafenib + cetuximab + FOLFIRI beat chemo in 1L BRAF V600E mCRC: PFS 15.2 vs 8.3 mo (HR 0.44), ORR 64%.
TARGETED WINStructured exercise after colon-cancer chemo improved 8-yr OS (HR 0.63) and saved money. Lifestyle as level-1 therapy.
LEVEL 1Lung
Ivonescimab beat a PD-1 + chemo backbone on OS (HR 0.66) in squamous NSCLC. China-only.
PLENARYSac-TMT (TROP2 ADC) + pembro vs pembro, 1L PD-L1+ NSCLC: PFS HR 0.38, ORR 70% vs 42%. China; OS pending.
TROP2 ADCFirst-line sunvozertinib beat platinum chemo on PFS (HR 0.65) in EGFR exon20ins NSCLC. An oral, chemo-free option.
1L ORALHematology
Teclistamab monotherapy cut progression-or-death 71% vs triplets at first relapse in myeloma.
POSITIVETafasitamab + lenalidomide + R-CHOP cut progression/death 25% in 1L high-risk DLBCL.
POSITIVEMezigdomide (next-gen CELMoD) + carfilzomib-dex beat Kd in relapsed/refractory myeloma. Beyond the IMiD era.
CELMoD LBASarcoma
Abemaciclib lifted PFS to 9.7 vs 1.5 mo in dedifferentiated liposarcoma. First positive phase 3 in the disease.
FIRST WINWHAT LANDED
Daraxonrasib
A pill moved OS in pancreatic cancer.
WHAT HELD
CROWN 1L ALK+
Lorlatinib stands, seven years on.
WHAT TO WATCH
PROTEUS label
Promising, not yet approved.
NEXT RADAR
EHA 2026
Stockholm, Jun 11-14. Heme takes the stage.
CONFERENCE RADAR 2026
Jun 11-14 · Stockholm · Hematology: bispecifics, CAR-T, myeloma
JUNE
Best of ASCO 2026
July · Curated highlights from the Annual Meeting
JULY
Oct 23-27 · Madrid · European late-breaking readouts
OCT
Dec 12-15 · New Orleans · Heme: myeloma, lymphoma, CAR-T
DEC
THE HOT TAKE
ISSUE 02 · 3 JUNE 2026
DR. SIGNAL · OPINION
The number you'll hear all week is only 8.5 months deep.
Daraxonrasib is the most important pancreatic result in a decade. I am not arguing with the biology. RAS finally got drugged, and patients lived longer. That earned every second of the standing ovation in Chicago.
But "doubled survival" is a headline, not a destiny. Median follow-up is 8.5 months, and young curves move. The honest framing this week is not "13.2 months." It is "13.2 months, so far, in a trial still maturing." Quote the second version to your patients.
And the question almost nobody on the plenary stage asked: this is a daily oral pill that will be priced for wealthy systems, for a cancer that kills fastest where it will never be stocked. The science crossed a line this week. Access has not. Name that gap now.
This is opinion, not consensus. Dr. Signal's take is one reading of the evidence - argue with it, that is the point.
THE VERDICTS, STAMPED
QUICK POLL
Daraxonrasib in pretreated mPDAC, the moment you can access it:
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