ESMO 2024: Recommendations From Dr. Elizabeth Smyth for Gastrointestinal Cancer

Dr. Elizabeth Smyth, Consultant Medical Oncologist at Oxford University Hospitals NHS Foundation Trust and member of the Advisory Board of PracticeUpdate Oncology, recommends the following abstracts being presented at this year’s ESMO Congress, held September 13 through 17, 2024, in Barcelona.

Saturday, September 14, 2024
8:30 AM–10:00 AM CEST; Proffered Paper Session 2

GI Tumours, Upper Digestive

LBA58 A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): final results from an intergroup trial of AGITG, TROG, EORTC and CCTG. T Leong

• TOPGEAR is an important academic trial which looks at the benefit of adding radiotherapy to neoadjuvant chemotherapy in operable gastric and gastroesophageal cancer. There is a major unmet need to improve outcomes for this patient group, as currently only 50% of patients are cured of their cancer following chemotherapy and surgery.

1401O Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). YY Janjigian

• For patients with HER2-positive GEA, historically, trastuzumab in combination with chemotherapy was the standard of care, but outcomes were very modest compared with those among patients with HER2-positive breast cancer. The KEYNOTE-811 trial demonstrated the efficacy of combining chemotherapy and trastuzumab with pembrolizumab, but importantly only for patients who were double-biomarker positive. This key finding, regarding the importance of immune context, was highlighted again in updated results presented at ESMO. Although KEYNOTE 811 was initially a statistically negative trial overall, the combination of triple therapy improved overall survival for HER2- and PD-L1–positive patients (who represented the majority of the population, 85%) sufficiently for this to become a standard of care. The results presented at ESMO 2024 updated the statistical significance of the trial to positive. Importantly, a detriment in overall survival was seen when pembrolizumab was added to chemotherapy and trastuzumab for HER2-positive PD-L1–negative patients, and immune checkpoint inhibitors are not recommended for this group of patients.
• Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate targeting HER2, is established as standard of care in HER2-positive GEA after progression on trastuzumab. In the DESTINY-Gastric03 trial, the first results of T-DXd in first-line HER2-positive GEA are shown. T-DXd as monotherapy showed comparable results in the first line compared with second-line therapy. The addition of 5-FU also increased response rates in all patients. However, adding pembrolizumab to T-DXd improved results only for PD-L1–positive patients, and it may have had a detriment in ORR in PD-L1–negative patients. These results underscore the results of KEYNOTE-811, in that HER2-positive GEA is comprised of two distinct biological entities, which should be treated differently according to PD-L1 status. Finally, interstitial lung disease (ILD), which is a previously identified concern for many antibody–drug conjugates, was identified in 11% of patients, with some deaths occurring. Early detection and timely management of ILD will be important in any ensuing registration trials in the first-line setting.

Monday, September 16, 2024
8:30 AM–10:00 AM CEST; Mini Oral Session

GI Tumours, Upper Digestive

LBA60 Phase 3 study of SHR-1701 versus placebo in combination with chemo as first-line (1L) therapy for HER2-negative gastric/gastroesophageal junction adenocarcinoma (G/GEJA). Z Peng