In a recent interview with CancerNetwork®, Nicholas Hornstein, MD, PhD, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, discussed emerging data and clinical shifts in the care of patients with gastrointestinal (GI) cancers ahead of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

Advancements in Colorectal Cancer

Hornstein highlighted the increasing integration of targeted therapies into the first-line setting for patients with colorectal cancer (CRC). For those with BRAF V600E-mutated metastatic disease, data from the phase 3 BREAKWATER trial (NCT04607421) support moving targeted therapy into the first line.1 He noted that initiating these therapies early is critical, as a significant percentage of patients may experience rapid clinical decline and lose the opportunity for second-line treatment if targeted options are delayed.

In the HER2-positive space, clinicians currently utilize tucatinib (Tukysa)-based regimens or fam-trastuzumab deruxtecan-nxki (Enhertu). Hornstein also anticipated the arrival of bispecific antibodies, such as zanidatamab-hrii (Ziihera), which are expected to gain approval in upper GI cancers before moving into the CRC landscape.

The Role of ctDNA and Pancreatic Cancer

Regarding localized disease, Hornstein discussed the potential for circulating tumor DNA (ctDNA) to guide adjuvant therapy for patients with stage II colon cancer. Data from trials like CIRCULATE (NCT05174169) are expected to further clarify how ctDNA can assist in the escalation or de-escalation of treatment.2 In pancreatic cancer, the phase 3 RASolute 302 trial (NCT06625320) investigating daraxonrasib is poised to change the standard of care for patients with second-line pancreatic cancer immediately upon an anticipated regulatory approval.3

Barriers to Precision Medicine

A primary unmet need that Hornstein identified was the low rate of biomarker testing; currently, only about half of patients with metastatic disease receive necessary sequencing or microsatellite instability testing. Hornstein emphasized that multidisciplinary cooperation and improved systems are essential to ensure all patients with targetable mutations receive appropriate care. Finally, he highlighted the development of large language model tools to assist clinicians with data ingestion and clinical trial matching.

References

1. Kopetz S, Wasan HS, Yoshino T, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.13

2. Dasari A, Yu G, Kopetz S, et al. NRG-GI008: colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA). J Clin Oncol. 2026;44(suppl 16):TPS3686. doi:10.1200/JCO.2026.44.16_suppl.TPS3686

3. Wolpin B, Wainberg ZA, Hendifar A, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5