GI Oncology saw some major changes in NCCN this week. 🔥 🧬 1. Daraxonrasib is officially in the pancreatic cancer guidelines You knew it was coming, now it is here. Preferred, Category 1. Use it. RASolute-302 in previously treated metastatic PDAC: OS: 13.2 vs 6.6 months, HR 0.40 PFS: 7.3 vs 3.5 months, HR 0.45 Subsequent therapy, and importantly it also sneaks into 1L as “useful in certain circumstances,” although only 2B for fit patients (but still there, YAY). So no, we are not throwing FOLFIRINOX/NALIRIFOX in the garbage (yet). But a RAS inhibitor is now a standard treatment for pancreatic cancer. 🔵 2. Zanidatamab + tislelizumab in NCCN for HER2+ GEA Zanidatamab + tislelizumab + chemo vs trastuzumab + chemo: PFS: 12.4 vs 8.1 months, HR 0.63 OS: 26.4 vs 19.2 months, HR 0.72 NCCN now lists zanidatamab-based therapy as Preferred first-line treatment. But… Category 2A. Why? 2A still means uniform NCCN panel consensus (≥85%) that the treatment is appropriate (so yes, you should be using this for these patients), but officially reflects lower-level evidence than Category 1. Except HERIZON was a randomized phase III trial with positive outcomes. So why 2A? Two informed guesses. 1. No US patients were enrolled. It was a large international study, and frankly the incredibly diverse patients I see in NYC probably look more like a global trial population than many historical US trials. 2. The control arm didn't include PD-1. HERIZON compared against trastuzumab + chemo, while our current US standard for PD-L1 CPS ≥1 is pembrolizumab + trastuzumab + chemo. But before we poo-poo HERIZON because of the comparator, let's look at what those studies actually achieved. KEYNOTE-811, CPS ≥1: PFS 10.9 months OS 20.1 months HERIZON: PFS 12.4 months OS 26.4 months Of course, no one would ever compared across trials. 😅 But HERIZON's own trastuzumab/chemo control arm had an OS of 19.2 months. This wasn't a control arm falling over. To me, these data show a real advance in HER2 therapy. If you’re using it, do watch for the diarrhea. NCCN specifically recommends antidiarrheal prophylaxis with zanidatamab and avoiding bolus 5-FU. Grade ≥3 diarrhea was 24.8% with the quadruplet but can be controlled and is only during the first few treatments. 3. And very briefly, MATTERHORN FLOT + durvalumab was upgraded 2B → 2A for PD-L1 <1 and diffuse-type EGJ adenocarcinoma. Overall MATTERHORN: 2-year EFS 67.4% vs 58.5%, HR 0.71, with pCR 19.2% vs 7.2%. Love seeing forward progress in GI Oncology. @TheGutOncLab @OncoAlert @Onco_Nexus @oncodaily

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

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