Dr Klempner: ASCO 2025 GI Cancer Insights and News
Samuel Klempner, MD, gastrointestinal medical oncologist, Oncology, Massachusetts General Hospital and faculty, Medicine, Harvard Medical School, shares crucial updates from the 2025 American Society of Clinical Oncology Annual Meeting concerning gastrointestinal (GI) cancers.
He highlights the ongoing unmet need in gastric cancers, emphasizing that while MATTERHORN (NCT04592913) is a "big step," more work is needed to cure more patients.1 Klempner discusses the emergence of new targets and drugs, including the first-ever positive chimeric antigen receptor (CAR) T-cell trial in solid tumors, specifically a Claudin18.2 CAR T in gastric cancer.
Other key takeaways include the phase 3 DESTINY-Gastric04 trial (NCT04704934)2, which solidifies fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) as the likely preferred second-line strategy for HER2-positive patients. Additionally, he touches on follow-up data from CheckMate 577 (NCT02743494)3 and significant advancements in colorectal cancer, particularly supporting immunotherapy in microsatellite instability-high (MSI) populations. Klempner concludes by pointing to highly anticipated future studies in upper GI, such as FGFR2 trials and the DANTE trial (NCT03421288), which he hopes will further support perioperative immunotherapy.
Transcription:
0:10 | Tons of data in GI and gastric and GEJ cancers and esophageal cancers. It is still an unmet need. MATTERHORN is a big step, but there's a lot more work to do. We want to cure more patients. There are a lot of new targets, new drugs, and some of the highlights we saw at ASCO, like we saw the first positive CAR T-cell trial in solid tumors ever, and it was a Claudin18.2 CAR T in gastric cancer [and] beat chemotherapy. We saw the phase 3 DESTINY-Gastric04 trial which basically solidified the idea of giving T-DXd in the second-line as probably the preferred strategy for HER2-positive patients. We saw follow-up data from CheckMate 577, [and] we saw a lot of things, even outside of the upper GI.
1:00 | We saw a lot of data in colorectal, you know, more evidence to support roles for immunotherapy, particularly in these MSI populations. So it was a big year for GI overall. [There are a] lot of things probably did not have time to cover, but we expect a lot more. I mean, there are some really highly anticipated studies in upper GI in the near future, like the FGFR2 trials. We have these 2 big phase 3 trials that we have been waiting to see, DANTE, which is another big perioperative trial, hopefully, will continue to support this idea of perioperative immunotherapy. So a lot of good stuff now, and a lot of good stuff to come.
REFERENCES:
Janjigian Y, Al-Batran S-E, Wainberg Z, et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2025;43(suppl 17):LBA5. doi:10.1200/JCO.2025.43.17_suppl.LBA5
Shitara K, Gumus M, Pietrantonio F, et al. Trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary analysis of the randomized, phase 3 DESTINY-Gastric04 study. Presented at: 2025 American Society of Clinical Oncology Annual Meeting; May 30-June 3, 2025. Chicago, IL. Abstract 4002.
Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): First results of overall survival (OS) from CheckMate 577. J Clin Oncol. 2025;43(suppl 16):4000. doi:10.1200/JCO.2025.43.16_suppl.4000
