Pt Adv, NCI Rectal Anal TF Mom Lifelong learner, Wants to bring pt voice to research clinical trials & more! Check out @CRCTrialsChat 1st love: Virology
Joined May 2011
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People seem ashamed to say they have/ are diagnosed with/survived #colorectalcancer.
Somehow it is a shameful thing…
We cannot raise awareness about CRC if we can only whisper *colorectal*
#crcsm #TheNewFaceOfCRC #crc45andunder
1/7
Manju George MVSc PhD retweeted
UNION's 24.5% pCR improvement w short course RT/IO impressive, but some context:
Control pCR only 15%, v 29% in GI002 & up to 38% in TIMING (both long course CRT/6c FOLFOX, no IO).
Hence magnitude of benefit may partly reflect less preop chemo in UNION control (just 2c CAPOX).
Full UNION paper is out in Lancet Oncol. Supplement Table S4 caught my eye: median time from RT start to surgery was 72 vs 113 days (SCRT/IO vs control), yet pCR was 39.8% vs 15.3%.
I would've expected LOWER pCR with surgery that much sooner(!), as we've seen in past short-course RT trials. Makes that response signal even more interesting!
Adding ICI in rectal cancer sure seems enticing! Are we entering a new frontier?!?
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#ASTRO26 STELLAR II (Li): phase 2/3, 588 pts w/ pMMR LARC, SCRT 25/5 → CAPOX x4 +/- sintilimab. Adding sintilimab increased CR (pCR + cCR) from 27% → 52% (p<0.001). pCR among operated pts went from 19% → 42%. G3-4 toxicity also went up, 20% → 28%. Looking forward to the primary phase 3 endpoint, 3y DFS, which is still pending.
---
#ASTRO26 TORCH-iTNT (Wang) asks a different question: randomized phase II, pMMR LARC, CAPOX + toripalimab x6 w/ vs w/o SCRT 25/5. CR was 37% w/o RT → 62% w/ SCRT. IO in both arms here.
---
Unlike UNION, both ASTRO trials allowed watch-and-wait / organ preservation, so CR includes cCR. These aren't all pCR comparisons. Oh and of course standard caveat that cross trial comparisons are a sin.
UNION enrolled only surgery-intended pts, and both arms got just 2 cycles of consolidation chemo vs the 4-6 now recommended. I wonder how this compares w/ modern TNT, especially when organ preservation is the goal.
doi.org/10.1016/s1470-2045(2…
#ESMO26 #radonc #OncTwitter #CRCSM
Manju George MVSc PhD retweeted
2.5 mg olanzapine will likely work as well
thelancet.com/journals/lanon…
Manju George MVSc PhD retweeted
#ESMO26
Mirtazapine or olanzapine for CINV prevention?
In a 120-pts randomized trial from India, mirtazapine achieved better complete control than olanzapine (46.2% vs 21.8%).
Promising, but too small and open-label to change practice. Congratulations to the investigators for their efforts👏👏
Manju George MVSc PhD retweeted
Ooo, supportive care. Easy win for patients.
Looks like swapping olanzapine out for mirtazapine significantly reduces nausea. Relevant to every oncologist.
Randomized trial from India at #ESMO26. 120 chemo-naive patients starting highly emetogenic chemo, randomized 1:1. Both arms got fosaprepitant + palonosetron + dex. Fourth drug was mirtazapine 15 mg vs olanzapine 5 mg, days 1–4.
Mirtazapine vs olanzapine:
Acute 78.5% vs 56.4%, p=0.01
Delayed 52.3% vs 25.5%, p=0.003
Overall 46.2% vs 21.8%, p=0.005
Major differences
120 patients? Minimal risk? I'm sold. The day after the paper comes out, I'll swap.
@realbowtiedoc thoughts?
@OncoAlert @TheGutOncLab @Onco_Nexus
Manju George MVSc PhD retweeted
More diarrhea, no DFS gain.
IROCAS (LBA29):
Randomized phase 3, 795 pts w/ R0-resected pT4 and/or N2 colon cancer: mFOLFIRINOX vs mFOLFOX6.
3-y DFS 65.6% vs 66.3% (HR 1.07). G≥3 diarrhea 15.6% vs 3.8%.
#ESMO26 #CRCSM
doi.org/10.1016/j.annonc.202…
Manju George MVSc PhD retweeted
We already know that ivonescimab is effective. However, something else caught my attention on this slide.
In the control arm, 7% of patients received “Traditional Chinese Medicine” as subsequent antitumor therapy, compared with only 0.6% in the ivonescimab arm.
What exactly are these treatments? Have they demonstrated any survival benefit, or is their efficacy no better than placebo?
And the crucial question: Could this imbalance have influenced OS, given the substantially higher use in the control arm?
Have similar treatments been reported in other randomized oncology trials?
#ESMO26
Manju George MVSc PhD retweeted
NICHE-2
💯 Primary endpoint met: 3-y DFS 100% (97.5% CI 100–100) vs prespecified 93% (p<0.0001).
5y OS 100% (exploratory post-hoc).
Grade 3–4 TRAE: 4% (previously reported); no new safety signals.
Wow!
#CRCSM
doi.org/10.1016/S0140-6736(2…
@PamelaKunzMD @OncoAlert
NICHE-2. Keeping it short because the plot speaks for itself.
1. Rename it Chalabi's disease
2. Stop operating on patients first
For those who don't know: 111 patients with locally advanced dMMR colon cancer got one dose of ipi and two of nivo, then surgery. Zero events. A flat line.
Next up? Avoid the surgery altogether.
#ESMO2026
@Onco_Nexus
@OncoAlert @TheGutOncLab
Manju George MVSc PhD retweeted
CRC has been a fascinating space for many years, but in 2026, wow... Just wow!
For example, switching gears from dMMR colon in NICHE-2 and going below the peritoneal reflection for pMMR rectal cancer, UNION, STELLAR II, and TORCH-iTNT have shown eye-popping response rates with a short-course RT backbone (?!) plus immunotherapy.
@NiuSanford @DrEmmaHolliday @nbn426 @KrishanJethwa @GIMedOnc @adapthyun @TimothyJBrownMD @manjuggm @OncoAlert @OncBrothers
#ASTRO26 #ESMO26 #OncTwitter #CRCSM
Full UNION paper is out in Lancet Oncol. Supplement Table S4 caught my eye: median time from RT start to surgery was 72 vs 113 days (SCRT/IO vs control), yet pCR was 39.8% vs 15.3%.
I would've expected LOWER pCR with surgery that much sooner(!), as we've seen in past short-course RT trials. Makes that response signal even more interesting!
Adding ICI in rectal cancer sure seems enticing! Are we entering a new frontier?!?
---
#ASTRO26 STELLAR II (Li): phase 2/3, 588 pts w/ pMMR LARC, SCRT 25/5 → CAPOX x4 +/- sintilimab. Adding sintilimab increased CR (pCR + cCR) from 27% → 52% (p<0.001). pCR among operated pts went from 19% → 42%. G3-4 toxicity also went up, 20% → 28%. Looking forward to the primary phase 3 endpoint, 3y DFS, which is still pending.
---
#ASTRO26 TORCH-iTNT (Wang) asks a different question: randomized phase II, pMMR LARC, CAPOX + toripalimab x6 w/ vs w/o SCRT 25/5. CR was 37% w/o RT → 62% w/ SCRT. IO in both arms here.
---
Unlike UNION, both ASTRO trials allowed watch-and-wait / organ preservation, so CR includes cCR. These aren't all pCR comparisons. Oh and of course standard caveat that cross trial comparisons are a sin.
UNION enrolled only surgery-intended pts, and both arms got just 2 cycles of consolidation chemo vs the 4-6 now recommended. I wonder how this compares w/ modern TNT, especially when organ preservation is the goal.
doi.org/10.1016/s1470-2045(2…
#ESMO26 #radonc #OncTwitter #CRCSM
Manju George MVSc PhD retweeted
TEMAB-A (ABBV-400) is an ADC focused on on cmet with topo 1 payload in a ph I trial of ABBV-400 + bev vs. TAS-102 + bev in previously treated metastatic #colorectal #cancer. @OncoAlert @oncodaily #ESMO2026
Median follow-up: 18.2 M
Median OS 14.7M and HR = 0.62
Proceeding onto Ph 3 trial: NCT06614192
@Cecchini_OncMD
Manju George MVSc PhD retweeted
Phase I encouraging results with INCB161734 (#KRAS #G12D) inhibitor 1200 mg + cetuximab (N=25) in #colorectal #cancer
- No grade 4/5 SAE's
- ORR = 36%
- DOR = 100%
- Median PFS = 7.2M
#ESMO2026 #RAS @Incyte @OncoAlert
Manju George MVSc PhD retweeted
💡What’s cool is the power of #ctDNA on multiple levels in CLOVER☘️Trial
1. It acted as a surrogate to early response
2. We were looking at 2 doses - we saw dose response
3. We were able to collaborate @NateraGenetics to find real world comparator
📈drug development @OncoAlert
Manju George MVSc PhD retweeted
UNION: PIII neoadjuvant rectal cancer 🇨🇳, presented at #ESMO26.
Basically PD1 + TNT vs TNT.
Positive on pCR and EFS. Does it change things? Very strong OS signal.
Design
• Locally advanced rectal cancer, 231 randomized
• Short-course RT → camrelizumab + CAPOX vs long-course chemoRT → CAPOX, then TME
Efficacy
pCR (BIRC, primary) 39.8% vs 15.3%, OR 3.65, p<0.0001
3-yr EFS 91.3% vs 77.4%, HR 0.33 (investigator)
3-yr OS 96.3% vs 89.8%, HR 0.35 (95% CI 0.11–1.10). Descriptive only, 15 deaths total.
Toxicity
Grade ≥3 TRAEs 51.3% vs 48.2%, mostly heme
Is the backbone appropriate?
Two things changed at once: the radiation schedule and the PD-1. The control arm is long-course CRT with CAPEOX, not the TNT most of us give today, and a 15% pCR is a low bar to clear.
Everyone went to TME, so the question US practice actually cares about, organ preservation, wasn't asked.
Still, an EFS HR of 0.33 at 3 years is considerable. I expect this’ll be standard in the future.
One thing I know, this study is done, and we're still only "planning" these PD1 studies in the US. Have to move faster.
@OncoAlert @TheGutOncLab @Onco_Nexus
Manju George MVSc PhD retweeted
Clinical Complete Response with Dostarlimab Monotherapy in dMMR/MSI-H Locally Advanced Rectal Cancer: First Results from the Global AZUR-1 Trial
#cancer #oncology #MedX #ESMO26 @OncoAlert
annalsofoncology.org/article…
Manju George MVSc PhD retweeted
AZUR-1 delivers. #ESMO26
Phase 2, single arm. Dostarlimab x 9 cycles (6 months) in untreated stage II/III dMMR/MSI-H rectal cancer, 154 patients.
Cercek's 49-patient NEJM cohort gone global.
No control arm, because randomizing these patients to TNT/TME isn't equitable.
cCR12 (complete response held 12+ months, no further treatment):
68% by investigator.
26% needed additional treatment
10% went to surgery
68% is likely lower than reality since many patients probably just needed more time to radiographically respond. Using PET/Biopsy/ctDNA, especially ctDNA, is incredibly helpful in my practice to identify patients who can avoid TME even if a fibrotic tumor remains as they often do.
FDA already gave accelerated approval (way to steal the ESMO thunder) last week which leads me to my next point.
Obvious new standard of care. You should go to oncology jail if you don't treat MSI-H with IO.
@OncoAlert @TheGutOncLab @Onco_Nexus
Manju George MVSc PhD retweeted
#ESMO26 Building upon options for our patients with #ColorectalCancer.
Our CLOVER☘️Trial
CCR5-targeting
Leronlimab with
Oral chemotherapy &
VEGF-inhibitor
Enriched
Regimen
#ctDNA reductions compared to real world+dose response
@OncoAlert @cityofhope
@benweinbergmd today!
Manju George MVSc PhD retweeted
📢 #ESMO26 concomitant paper - Clinical complete response with dostarlimab monotherapy in dMMR/MSI-H locally advanced rectal cancer: first results from the global AZUR-1 trial.
🔗tinyurl.com/2u2ymahj
@AndreaCercek
Manju George MVSc PhD retweeted
A targeted dual-protein lock. A completely new way of thinking about cancer therapy. #JNJ6143 is a first-in-class #RIPTAC™ oral small molecule designed to selectively bring together two proteins—AR and BRD4—inside prostate cancer cells, creating a ternary complex that disrupts cancer-driving biology and triggers tumor cell death. @BGarmezy showcased this at #ESMO2026 today and it has been the talk of the meeting! #ProstateCancer #Oncology #CancerResearch #PrecisionMedicine
Manju George MVSc PhD retweeted
📌 806P: Extended ctDNA sequencing to optimize patient selection for anti-EGFR re-treatment vs. alternative late-line therapies in RAS/BRAF wild-type metastatic colorectal cancer (PARERE and CITRIC trials)
📍 Poster Area - Hall 5
🗓️ Sunday, October 25th
🕒 12:00 – 12:45
#ESMO26
Manju George MVSc PhD retweeted
#ESMO26 | IROCAS
I think we can finally put this debate to rest
In high-risk stage III colon cancer, intensifying adjuvant chemotherapy with mFOLFIRINOX failed to improve DFS over mFOLFOX6
We need to rethink our approach to treatment escalation in the adjuvant setting. Simply adding more conventional cytotoxic agents is not the answer.
Manju George MVSc PhD retweeted
Full UNION paper is out in Lancet Oncol. Supplement Table S4 caught my eye: median time from RT start to surgery was 72 vs 113 days (SCRT/IO vs control), yet pCR was 39.8% vs 15.3%.
I would've expected LOWER pCR with surgery that much sooner(!), as we've seen in past short-course RT trials. Makes that response signal even more interesting!
Adding ICI in rectal cancer sure seems enticing! Are we entering a new frontier?!?
---
#ASTRO26 STELLAR II (Li): phase 2/3, 588 pts w/ pMMR LARC, SCRT 25/5 → CAPOX x4 +/- sintilimab. Adding sintilimab increased CR (pCR + cCR) from 27% → 52% (p<0.001). pCR among operated pts went from 19% → 42%. G3-4 toxicity also went up, 20% → 28%. Looking forward to the primary phase 3 endpoint, 3y DFS, which is still pending.
---
#ASTRO26 TORCH-iTNT (Wang) asks a different question: randomized phase II, pMMR LARC, CAPOX + toripalimab x6 w/ vs w/o SCRT 25/5. CR was 37% w/o RT → 62% w/ SCRT. IO in both arms here.
---
Unlike UNION, both ASTRO trials allowed watch-and-wait / organ preservation, so CR includes cCR. These aren't all pCR comparisons. Oh and of course standard caveat that cross trial comparisons are a sin.
UNION enrolled only surgery-intended pts, and both arms got just 2 cycles of consolidation chemo vs the 4-6 now recommended. I wonder how this compares w/ modern TNT, especially when organ preservation is the goal.
doi.org/10.1016/s1470-2045(2…
#ESMO26 #radonc #OncTwitter #CRCSM