Can a new HER2-targeted therapy improve outcomes for patients with gastroesophageal cancer? Professor Shen Lin from Peking University Cancer Hospital led the global Phase III HERIZON-GEA-01 study evaluating zanidatamab-based treatments for HER2-positive gastroesophageal adenocarcinoma. Compared with trastuzumab-based therapy, zanidatamab plus chemotherapy significantly prolonged progression-free survival. The combination of zanidatamab, tislelizumab, and chemotherapy also extended overall survival to 26.4 months, compared with 19.2 months for the standard treatment. Published in The New England Journal of Medicine (NEJM), the study highlights a promising new first-line treatment option for patients with HER2-positive gastroesophageal adenocarcinoma. Read more: #PKUResearch#

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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

FDA approves Eli Lilly’s $LLY Inluriyo + Verzenio for a form of advanced breast cancer driven by the ESR1 mutation. The treatment is for adults with ER-positive, HER2-negative advanced or metastatic disease and is now available in the U.S.

After a breast cancer diagnosis, one of the hardest questions is whether it will come back. @SimBioSys is helping doctors and patients better understand that risk. Powered by NVIDIA technology, its FDA-cleared TumorSight Risk analyzes an existing breast MRI alongside pathology and clinical information to estimate the risk of cancer returning at five and ten years. For women with HR-positive, HER2-negative early-stage breast cancer, those insights can be available before surgery, giving them and their doctors more information as they talk through treatment options. AI can help give patients and their doctors more information when the decisions ahead feel most difficult.

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