There is no such thing as “too young for cancer.” I keep writing this because apparently some people still need to read it. Our new @TheGutOncLab paper on early-onset cholangiocarcinoma is out, and the message is simple: Early-onset cancers aren't just a colorectal disease, and these patients are routinely ignored at diagnosis. Sydney Towle helped early onset cholangiocarcinoma into the public eye via TikTok, but her experience with delayed diagnosis was sadly the norm. Our data show the problem at scale. We looked at >116,000 patients with cholangiocarcinoma, including >5,000 diagnosed before 50. ❌ Younger patients had 24% higher odds of waiting >30 days for a diagnosis ⌛️ Median diagnostic delay was two months 🙍‍♀️ Young women were particularly affected The problem, as it seems, was getting to the diagnosis. Early-age cancer is bigger than #EACRC#. One liner? Young people get cancer too. When they tell us something is wrong, we should listen. Thanks for the opportunity to contribute @UGrewalMD @Onco_Nexus @OncoAlert @OncoDailyGI

Just landed in Bermuda for the DAVA GI Malignancies Summit. 🇧🇲 Everyone thinks conference = vacation. Most of the time, I barely make it outside the conference room. The goal is to develop relationships, come up with new ideas (or move old ones forward), and come home with at least one new study, treatment, or piece of knowledge that can help the patients I see on Monday. Grateful to be in the room and to be part of a GI oncology community that keeps pushing the science forward. There is always more to learn, more to build, and hopefully more we can do for our patients. Want to follow along virtually? And maybe, just maybe, I’ll make it to the beach this time. 🏖️ #DavaGI# @DAVAOnc @Onco_Nexus @TheGutOncLab @OncoAlert

Was great to put my hematology hat back on and work alongside @UGrewalMD and @TimothyJBrownMD on this accompanying JCO article where we propose a 3 part framework for bringing TPO agonists into routine clinical practice for GI Oncology patients. We have the right tools to help patients maintain dose intensity; we just need to use them. @OncoAlert @TheGutOncLab @Onco_Nexus

Clinical trials are among the most opaque parts of modern medicine. They can be dense and difficult to understand for clinicians, let alone patients. So, @TheGutOncLab recorded an episode designed to make clinical trials a little more approachable. Not just what they are, but how patients can find, evaluate, and enroll in them. This episode is geared more toward patients than clinicians, but we hope it is helpful for anyone looking for an entry point into the world of clinical trials. Video Below: Spotify: @OncoAlert @Onco_Nexus @oncodaily @cancerGRACE

New episode of @TheGutOncLab . With a twist: we got a surgeon on. 🔪 Dr. Robert Martin joined @TimothyJBrownMD and me to talk colorectal cancer liver metastases. CRLM is one of the few spaces in metastatic GI oncology where “curable” is still on the table. But the window is narrow, and biology matters. A few highlights: 🔪 The question is not just “can we remove it?” but “how and what should we remove it?” 🩸 ctDNA is getting hard to ignore, but it should not automatically mean “more chemo forever.” Repeat it. Watch the kinetics. Get the right imaging. Discuss as a team. Surgery with biology-first thinking. New episode out now with Dr. Robert Martin, @TimothyJBrownMD, and me. OncoNexus (Out Now): Spotify (To Be Posted 7/27): Apple (To Be Posted 7/27): @UGrewalMD @OncoAlert @Onco_Nexus

This is the daraxonrasib news I’ve been refreshing the RevMed site for! The NDA has been accepted for FDA review. And before anyone says it: no, this is not “late.” NDA packets are enormous. Clinical data, CMC, safety, labeling, subgroup analyses, QA, regulatory back-and-forth. It takes time to package a drug for FDA review, especially when the goal is not “nice phase 1 signal” but actual approval. Now the timer starts. ⏱️ Why does this matter? An oral RAS inhibitor with phase 3 PFS and OS benefit is a big deal. I think we've all said that enough by now. Now the FDA gets to do what it has said it wants to do: Get life-saving drugs into patients’ hands as quickly as possible (outside of an EAP program). FDA clock officially started. ⏱️ @TheGutOncLab @OncoAlert @oncodaily @Onco_Nexus

New episode of the @TheGutOncLab ! Pancreatic cancer is finally be entering a true era of targeted therapy (and no, this isn't just another discussion of RAS, although it does come up). In this episode of we have special guest and queen of pancreatic cancer, @KReissMD who join myself, @TimothyJBrownMD, and @UGrewalMD to discuss why 2026 feels different in PDAC. BRCA/PALB2-directed treatment. PARP maintenance. The next wave of RAS-targeted therapies. The pipeline is moving quickly, and for the first time in a long time, there is real momentum beyond chemotherapy. 🎧 Watch the full episode (with video) on OncoNexus: Spotify: @Onco_Nexus @OncoAlert @oncodaily

RELIGHT: PIII 1L gastric cancer 🇨🇳, now published in JCO. "Positive", but put it next to CheckMate and it suddenly loses its luster. Retlirafusp is a PD-L1/TGF-B bispecific. The study randomized 731 patients with HER2-negative gastric/GEJ adenocarcinoma to retlirafusp + CAPOX vs placebo + CAPOX. OS 16.8 vs 10.4 mo, HR 0.53 PFS 7.6 vs 5.5 mo, HR 0.52 Looking at the Chinese cohort in CheckMate-649, CPS ≥5 cohort (nivo + chemo vs chemo) results are strikingly similar: OS 15.5 vs 9.6 mo, HR 0.54 PFS 8.5 vs 4.3 mo, HR 0.52 Given a plain PD-1 inhibitor produced essentially the same hazard ratios here it is hard to see what TGF-β is adding. Chemo alone hasn't been standard for years, and the authors acknowledge the protocol was locked before PD-1 + chemo became SoC in China. RELIGHT shows retlirafusp beats chemo; we already knew that. Why am I posting about it? Well, it is another striking example that China has woken up to clinical trials and is running laps around the rest of the world in terms of speed, cost and efficiency. Anyone who has watched a trial sit in contracting for months knows reform is overdue (someone please teach me how to efficiently move legal forward). @OncoAlert @TheGutOncLab @Onco_Nexus

World Lung is in full swing, which means the press releases are coming fast (before the papers or the sessions). 🫁 Why do we care in GI? Because all the shiny things start in lung and eventually make their way over here. HARMONi-2 compared ivonescimab vs pembrolizumab in PD-L1+ advanced NSCLC. We already knew the PFS result was kind of wild (in a China-only study): 11.1 vs 5.8 months HR 0.51 Now OS: 🔥 30.8 vs 22.6 months 🔥 HR 0.73 PD-L1 ≥50%: HR 0.58 PD-L1 1–49%: HR 0.85 So now this PD-1 x VEGF bispecific has beaten pembrolizumab for both PFS and OS in a randomized phase III trial. Yes, China only. Yes, pembro monotherapy is not really the comparator most of us would want for PD-L1 1–49%. Still. An 8-month OS difference is quite a bit. GI oncologists should be paying attention because this is already cooking in the first line mCRC setting with HARMONi-GI3. mFOLFOX6 + ivonescimab vs mFOLFOX6 + bevacizumab Is this an end-run around patent protection laws and PD1/PDL1's run out of time? (yes) Does the strategy have synergystic benefit? Time will tell. @OncoAlert @TheGutOncLab @Onco_Nexus

And just like that, adagrasib + cetuximab is no longer FDA approved for KRAS G12C colorectal cancer. The accelerated approval was officially withdrawn September 1 after KRYSTAL-10 failed to confirm benefit. We talked about KRYSTAL-10 when it was presented earlier this year. The phase III randomized 461 patients in 2L to adagrasib + cetuximab vs chemotherapy ± VEGF inhibition. It missed both primary endpoints: ▪️PFS: 7.5 vs 8.1 months, HR 0.89
▪️OS: 21.6 vs 21.7 months, HR 0.83 Hard to argue with a negative phase III trial. But I still like the idea of a chemo free option. Response rate was 47% vs 16%. That could matter for some patients (like those who you need just a little more shrinkage to enable crative intent therapy). KRYSTAL-10 asked whether adagrasib + cetuximab was better than chemotherapy in 2L. It wasn’t. That doesn’t mean the concept of KRAS G12C + EGFR blockade was wrong. And it doesn’t mean there aren’t patients for which this isnt valuable. Anyone celebrating this should look themselves in the mirror; this is a tool that has just been removed from our arsenal. However, the FDA did exactly what the system is designed to do; pull back if the Ph III doesnt pan out after accelerated approval. @OncoAlert @TheGutOncLab @Onco_Nexus