Expert Perspectives on 2024 ASCO GI Cancers Symposium Trial Updates

After the 2024 Gastrointestinal Cancers Symposium, Jun Gong, MD, and Daneng Li, MD, sat down to discuss the most relevant trial data to have come from the conference. They convened for a live X Space hosted by CancerNetwork^®.

During the discussion, they covered different trials across the gastrointestinal space, which included those evaluating different disease states from hepatocellular carcinoma (HCC) to colorectal cancer (CRC), and those assessing circulating tumor DNA (ctDNA) dynamics.

Gong, a hematologic oncologist focusing on gastrointestinal and genitourinary cancers at Cedars-Sinai Medical Center, and Li, an associate professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, each gave their perspective on the clinical trial data and discussed if they had implemented any of these study treatments into clinical practice.

The studies they covered included:

• Phase 3 NETTER-2 Trial (NCT03972488)¹:
  • Investigated lutetium Lu 177 dotatate (Lutathera) plus octreotide vs octreotide alone for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
  • Lutetium Lu 177 significantly improved progression-free survival (PFS) and overall response rate (ORR) compared with octreotide alone.
  • The agent may be considered for patients with high-grade GEP-NETs who desire significant tumor shrinkage.
• Phase 3 EMERALD-1 Trial (NCT03778957)²:
  • Studied transarterial chemoembolization (TACE) plus durvalumab (Imfinzi) with or without bevacizumab (Avastin) for unresectable HCC.
  • Durvalumab/bevacizumab plus TACE improved PFS compared with placebo plus TACE.
  • TACE may be preferred over transarterial radioembolization (TARE) due to faster patient recovery.
• Phase 3 CheckMate-8HW Trial³:
  • Evaluated nivolumab (Opdivo) plus ipilimumab (Yervoy) vs chemotherapy for first-line treatment of microsatellite instability-high/mismatch repair deficient metastatic CRC.
  • Nivolumab/ipilimumab demonstrated superior PFS compared with chemotherapy.
  • Chemotherapy may no longer be the standard first-line treatment for this patient population.
• BESPOKE Study (NCT04264702)⁴:
  • Assessed the impact of minimal residual disease (MRD) detected by ctDNA on disease recurrence in patients with stage II and III CRC receiving adjuvant chemotherapy.
  • MRD positivity was associated with worse disease-free survival (DFS).
  • ctDNA clearance at 12 weeks indicated improved DFS.
• GALAXY Trial⁵:
  • ctDNA is a promising biomarker that can be used to predict recurrence in patients with CRC.
  • Patients with ctDNA-positive disease had a worse DFS than patients with ctDNA-negative disease.
  • This suggests that ctDNA may be useful for making treatment decisions, but more research is needed before it can be used in clinical practice.
• Phase 3 FRESCO-2 Trial (NCT04322539)⁶:
  • Fruquintinib (Fruzaqla) improved the quality of life in patients with metastatic CRC when combined with best supportive care and significantly improved quality-adjusted time without symptoms of disease or toxicity compared with placebo and best supportive care.
  • The study showed positive effects on PFS, response rate, disease control, and duration of response with the fruquintinib combination.
  • The findings from this trial supported the FDA approval of fruquintinib for metastatic CRC in November 2023.⁷

References

1. Singh S, Halperin D, Myrehaug S, et al. [177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: primary analysis of the phase 3 randomized NETTER-2 study. J Clin Oncol. 2024(suppl 3):LBA588. doi:10.1200/JCO.2024.42.3_suppl.LBA588
2. Lencioni R, Kudo M, Erinjeri J, et al. EMERALD-1: a phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. J Clin Oncol. 2024;42(suppl 3):LBA432. doi.10.1200/JCO.2024.42.3_suppl.LBA432
3. Andre T, Elez E, Van Cutsem E, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. J Clin Oncol. 2024;42(suppl_3):LBA768. doi.10.1200/JCO.2024.42.3_suppl.LBA768
4. Kasi P, Aushev V, Ensor J, et al. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): interim analysis of BESPOKE CRC study. J Clin Oncol. 2024;42 (suppl _3):9. doi:10.1200/JCO.2024.42.3_suppl.9
5. Yukami H, Nakamura Y, Mishima S, et al. Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. J Clin Oncol. 2024;42(suppl_3):6. doi:10.1200/JCO.2024.42.3_suppl.6
6. Stintzing S, Tabernero J, Satoh T, et al. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): results from the FRESCO-2 trial. J Clin Oncol. 2024;42(suppl 3):116. doi:10.1200/JCO.2024.42.3_suppl.116
7. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. News release. November 8, 2023. Accessed February 7, 2024. https://shorturl.at/isJW2