Therapeutic Advances in the Treatment of Gastroesophageal Cancers
Abstract
:1. Introduction
2. Localized Disease
3. Metastatic Disease
3.1. First Line Systemic Therapies
3.2. Second Line and beyond Systemic Therapies
3.3. Other Targeted Therapies
4. Emerging Therapeutics
4.1. Claudin 18.2
4.2. FGFR2
4.3. DKK1
4.4. Tyrosine Kinase Inhibitors
4.5. Others
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Trial | Treatment Regimen | Treatment Setting | Disease Site | Histologic Subtype | Biomarker |
---|---|---|---|---|---|
KEYNOTE-811 | Chemotherapy + trastuzumab + pembrolizumab | 1L | Gastric, GEJ | AC | HER2 positive, PD-L1 agnostic |
CheckMate 649 | Chemotherapy + nivolumab | 1L | Esophageal, Gastric, GEJ | AC | HER2 negative, PD-L1 CPS ≥ 5 |
KEYNOTE-590 | Chemotherapy + pembrolizumab | 1L | Esophageal, GEJ | AC, SCC | HER2 negative, PD-L1 CPS ≥ 10 |
CheckMate 648 | Chemotherapy + nivolumab, ipilimumab + nivolumab | 1L | Esophageal | SCC | HER2 negative, PD-L1 TPS ≥ 1 |
DESTINY-Gastric01 | Trastuzumab deruxtecan | 2L+ | Gastric, GEJ | AC | HER2 positive |
KEYNOTE-181 | Pembrolizumab | 2L+ | Esophageal | SCC | HER2 negative, PD-L1 CPS ≥ 10 |
ATTRACTION-3 | Nivolumab | 2L+ | Esophageal | SCC | HER2 negative, PD-L1 agnostic |
Study Title | Phase | Intervention | Treatment Setting | Conditions | NCT Identifier | Biomarker/Target |
---|---|---|---|---|---|---|
A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer (SPOTLIGHT) | 3 | FOLFOX + Zolbetuximab | Metastatic/Advanced 1L | Gastric AC, GEJ AC | NCT03504397 | Claudin 18.2 |
A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW) | 3 | CAPOX + Zolbetuximab | Metastatic/Advanced 1L | Gastric AC, GEJ AC | NCT03653507 | Claudin 18.2 |
A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of Zolbetuximab (IMAB362) in Participants With Claudin (CLDN) 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma (ILUSTRO) | 2 | Zolbetuximab, Zolbetuximab + FOLFOX, Zolbetuximab + pembrolizumab, Zolbetuximab + FOLFOX ± nivolumab | Metastatic/Advanced 1L/3L+ | Gastric AC, GEJ AC | NCT03505320 | Claudin 18.2 |
A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer (FIGHT) | 2 | FOLFOX + Bemarituzumab | Metastatic/Advanced 1L | Gastric AC, GEJ AC | NCT03694522 | FGFR2b |
Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (FORTITUDE-101) | 3 | FOLFOX + Bemarituzumab | Metastatic/Advanced 1L | Gastric AC, GEJ AC | NCT05052801 | FGFR2b |
A Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy in Patients With Gastric or Gastroesophageal Cancer (DisTinGuish) | 2 | FOLFOX/CAPOX + tislelizumab + DKN-01 | Metastatic/Advanced 1L/2L | Gastric AC, GEJ AC | NCT04363801 | DKK1 |
Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014) | 3 | Pembrolizumab + lenvatinib + chemotherapy | Metastatic/Advanced 1L | Esophageal SCC | NCT04949256 | TKI |
Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015) | 3 | Pembrolizumab + lenvatinib + chemotherapy | Metastatic/Advanced 1L | Gastroesophageal AC | NCT04662710 | TKI |
Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma | 2 | Atezolizumab + cabozantinib | Metastatic/Advanced 2L | Esophageal SCC | NCT05007613 | TKI |
Study To Investigate the Efficacy and Safety of Sitravatinib in Combination With Tislelizumab in Participants With Esophageal Squamous Cell Carcinoma | 2 | Tislelizumab + sitravatinib | Metastatic/Advanced 2L+ | Esophageal SCC | NCT05461794 | TKI |
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Li, J.J.; Rogers, J.E.; Yamashita, K.; Waters, R.E.; Blum Murphy, M.; Ajani, J.A. Therapeutic Advances in the Treatment of Gastroesophageal Cancers. Biomolecules 2023, 13, 796. https://doi.org/10.3390/biom13050796
Li JJ, Rogers JE, Yamashita K, Waters RE, Blum Murphy M, Ajani JA. Therapeutic Advances in the Treatment of Gastroesophageal Cancers. Biomolecules. 2023; 13(5):796. https://doi.org/10.3390/biom13050796
Chicago/Turabian StyleLi, Jenny J., Jane E. Rogers, Kohei Yamashita, Rebecca E. Waters, Mariela Blum Murphy, and Jaffer A. Ajani. 2023. "Therapeutic Advances in the Treatment of Gastroesophageal Cancers" Biomolecules 13, no. 5: 796. https://doi.org/10.3390/biom13050796
APA StyleLi, J. J., Rogers, J. E., Yamashita, K., Waters, R. E., Blum Murphy, M., & Ajani, J. A. (2023). Therapeutic Advances in the Treatment of Gastroesophageal Cancers. Biomolecules, 13(5), 796. https://doi.org/10.3390/biom13050796