Rutika Mehta: Key Lower GI Studies to Watch at ASCO26

Rutika Mehta, GI Medical Oncologist and Associate Professor at Weill Cornell Medicine, shared a post on LinkedIn:

”Key Lower GI studies to follow at ASCO26 – a quick summary of what I’m watching in colorectal cancer this year.

From novel ADCs to ctDNA-guided therapy and AI biomarkers, this meeting is reshaping how we think about personalizing CRC treatment. Here are the highlights:

Top 5 insights:

•  Trastuzumab rezetecan is a practice-changer – nearly doubles PFS with an ORR of 40.7% in HER2+ CRC. Test for HER2.
• ctDNA is everywhere at ASCO26 – GALAXY, CodeBreaK 300, and MSI-H real-world data all confirm it as a powerful response/prognostic tool.
• CHAI mCRCpred – AI on H&E slides predicts who benefits from FOLFOXIRI vs doublet. The era of digital pathology biomarkers is here.
•  In dMMR/MSI-H CRC achieving cCR on PD-1 therapy: stop treatment. Maintenance adds toxicity without survival benefit per the NOM cohort study.
•  CHALLENGE trial economic analysis: a structured exercise program is literally less expensive AND more effective than standard health education. Prescribe exercise.

Still awaiting:

1. LBA3500 – CIRCULATE (AIO KRK-0217/ABCSG) A phase III German-Austrian trial testing whether ctDNA status at diagnosis should determine whether stage II colon cancer patients receive adjuvant chemotherapy. Patients with detectable ctDNA post-surgery were directed toward chemo; those without were observed. This is a landmark study addressing overtreatment in a population where most patients are cured by surgery alone
2. LBA3503 – BREAKWATER A phase III trial of first-line encorafenib + cetuximab + FOLFIRI in BRAF V600E-mutant mCRC – a population with historically poor prognosis on standard chemotherapy. PFS and OS data to be released
3. LBA3506 – PUMP Trial A Dutch randomized controlled trial evaluating whether adjuvant hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine, delivered directly into the liver vasculature, improves outcomes in patients with resectable colorectal liver metastases who have a low clinical risk score.
4. LBA3508 – EPISODE-III (JCOG1503C) A Japanese phase III double-blind, placebo-controlled trial of adjuvant aspirin in stage III CRC after curative resection. Motivated by observational data showing aspirin’s COX-2-mediated anti-tumor effects in CRC
5. LBA3509 – Tunlametinib + Vemurafenib A Chinese phase III trial testing a MEK inhibitor (tunlametinib) combined with a BRAF inhibitor (vemurafenib) vs investigator’s choice in previously treated BRAF V600E mCRC. Dual vertical pathway blockade is the same rational strategy as encorafenib + binimetinib
6. LBA3515 – mRCAT-III A Chinese phase III trial in pMMR/MSS locally advanced rectal cancer comparing a novel ‘node-sparing modified short-course radiotherapy’ combined with CAPOX and the PD-1 inhibitor tislelizumab against conventional short-course preoperative chemoradiotherapy. Addresses whether immunotherapy can be meaningfully integrated into rectal cancer neoadjuvant treatment for the MSS (immunotherapy-resistant) population.”

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