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Guidelines

Type of Cancer Link to Guidelines
GEA https://doi.org/10.5858/arpa.2016-0331-CP
GEA https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf
GEA https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf
BTC https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf

Approved and investigational first-line and second-line therapies in advanced GEA

First-line Therapies
Therapy Clinical Trial Reference
Trastuzumab + Chemotherapy (fluorouracil or capecitabine + cisplatin) ToGA https://pubmed.ncbi.nlm.nih.gov/20728210/
Trastuzumab + Chemotherapy HELOISE https://pubmed.ncbi.nlm.nih.gov/28574779/
Pertuzumab, Trastuzumab, Chemotherapy vs Trastuzumab, chemotherapy JACOB https://pubmed.ncbi.nlm.nih.gov/30217672/
Pembrolizumab/placebo + trastuzumab + chemotherapy KEYNOTE-811 https://pubmed.ncbi.nlm.nih.gov/37871604/
Pembrolizumab, trastuzumab, chemotherapy NCT02954536, NCT02901301 https://ascopubs.org/doi/10.1200/JCO.2019.37.4_suppl.62
Trastuzumab + nivolumab + ipilimumab OR nivolumab + FOLFOX + trastuzumab INTEGA/ NCT03409848 https://clinicaltrials.gov/study/NCT03409848
Neoadjuvant trastuzumab OR trastuzumab + pertuzumab with chemotherapy INNOVATION/ NCT02205047 https://clinicaltrials.gov/study/NCT02205047
Zanidatamab + chemotherapy with/without tislelizumab HERIZON-GEA-01 https://www.clinicaltrials.gov/study/NCT05152147
Zanidatamab + chemotherapy with/without tislelizumab NCT04276493 https://www.clinicaltrials.gov/study/NCT04276493
Zanidatamab + tislelizumab NCT05270889 https://www.clinicaltrials.gov/study/NCT05270889
Zanidatamab + combination chemotherapy NCT03929666 https://www.clinicaltrials.gov/study/NCT03929666
Second-line Therapies
Therapy Clinical Trial Reference
Lapatinib + chemotherapy vs chemotherapy TyTAN https://pubmed.ncbi.nlm.nih.gov/24868024/
Lapatinib + chemotherapy vs chemotherapy LOGiC https://pubmed.ncbi.nlm.nih.gov/26628478/
Trastuzumab deruxtecan versus physicians’ choice DESTINY-Gastric01/ NCT03329690 https://www.nejm.org/doi/full/10.1056/NEJMoa2004413
TD-MI vs taxane GATSBY https://pubmed.ncbi.nlm.nih.gov/28343975/
Taxanes vs trastuzumab + paclitaxel T-ACT https://pubmed.ncbi.nlm.nih.gov/32208960/
Afatinib + paclitaxel NCT02501603 https://clinicaltrials.gov/study/NCT02501603
Margetuximab + pembrolizumab NCT02689284 https://ascopubs.org/doi/10.1200/JCO.2018.36.4_suppl.140
Margetuximab + pembrolizumab CP-MGAH22-05 https://pubmed.ncbi.nlm.nih.gov/32653053/
Trastuzumab + ramucirumab + paclitaxel HER-RAM https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.330
HER2-targeted CAR T-cells NCT02713984 https://clinicaltrials.gov/study/NCT02713984
Varlitinib/placebo plus mFOLFOX6 NCT03130790 https://clinicaltrials.gov/study/NCT03130790
Neratinib monotherapy SUMMIT/ NCT01953926 https://pubmed.ncbi.nlm.nih.gov/29420467/
KN026 Phase 2 study, China https://pubmed.ncbi.nlm.nih.gov/36370604/

Approved and Investigational first-line and second-line therapies in advanced BTC

First-line Therapies
Therapy Clinical Trial Reference
Tucatinib + trastuzumab + pembrolizumab + FOLFOX + CAPOX NCT04430738 https://clinicaltrials.gov/study/NCT04430738
Trastuzumab-pkrb + gemcitabine and cisplatin Pilot study https://pubmed.ncbi.nlm.nih.gov/33418871/
Second-line Therapies
Therapy Clinical Trial Reference
T-DXd DESTINY-PanTumor02 (NCT04482309) https://ascopubs.org/doi/10.1200/JCO.23.02005
Capecitabine + varlitinib TreeTopp https://pubmed.ncbi.nlm.nih.gov/34922298/
Pertuzumab + trastuzumab My Pathway (NCT02091141) https://pubmed.ncbi.nlm.nih.gov/34339623/
Neratinib monotherapy SUMMIT/NCT01953926 https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4079
T-DXd HERB https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.4006
Tucatinib + Trastuzumab SGNTUC-019 NCT04579380 https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1105
Zanidatamab HERIZON-BTC-01 https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4008
RC48 NCT04329429 https://clinicaltrials.gov/study/NCT04329429
MRG002 NCT04837508 https://clinicaltrials.gov/study/NCT04837508
Lapatinib ditosylate NCT00107536 https://clinicaltrials.gov/study/NCT00107536
Zanidatamab HERIZON-BTC-01 NCT04466891 https://clinicaltrials.gov/study/NCT04466891
Zanidatamab + bevacizumab + chemotherapy NCT03929666 https://clinicaltrials.gov/study/NCT03929666
Trastuzumab-pkrb + mFOLFOX NCT04722133 https://clinicaltrials.gov/study/NCT04722133
RC48 + Envafolimab (anti-PD-L1) NCT05417230 https://clinicaltrials.gov/study/NCT05417230
RC48 + GLS-010 (anti-PD-1) RIGHT NCT05540483 https://clinicaltrials.gov/study/NCT05540483
GQ1001 NCT04450732 https://clinicaltrials.gov/study/NCT04450732
CT-0508 (CAR macrophages) NCT04660929 https://clinicaltrials.gov/study/NCT04660929
DB-1303 NCT05150691 https://clinicaltrials.gov/study/NCT05150691
Trastuzumab emtansine KAMELEON NCT02999672 https://clinicaltrials.gov/study/NCT02999672
Lapatinib NCT00101036 https://clinicaltrials.gov/study/NCT00101036

References

  1. Bang YJ, Custem EV, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. 2010;376:687-697. doi:10.1016/S0140-6736(10)61121-X
  2. Shah MA, Xu RH, Bang YJ, et al. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017;35:2558-2567. doi:10.1200/JCO.2016.71.6852
  3. Tabernero J, Hoff PM, Shen L, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): Final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018;19:1372-1384. doi:10.1016/S1470-2045(18)30481-9
  4. Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: Interim analyses from the phase 3 KEYNOTE-811 randomized placebo-controlled trial. Lancet. 2023;402:2197-2208. doi:10.1016/S0140-6736(23)02033-0
  5. Janjigian YY, Chou J, Simmons M, et al. First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma (mEGA). J Clin Oncol. 2019;37:62. doi:10.1200/JCO.2019.37.4_suppl.62
  6. Satoh T, Xu RH, Chung HC, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN—a randomized, phase III study. J Clin Oncol. 2014;32:2039-2049. doi:10.1200/JCO.2013.53.6136
  7. Hecht JR, Bang YJ, Qin SK, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC–a randomized phase III trial. J Clin Oncol. 2016;34:443-451. doi:10.1200/JCO.2015.62.6598
  8. Shitara K, Bang YJ, Iwasa S, et al. DESTINY-Gastric01 Investigators. Trastuzumab deruxtecan in previously treated HER2-Positive gastric cancer. New Engl J Med. 2020; 382:2419-2430. doi:10.1056/NEJMoa2004413
  9. Hyman DM, Piha-Paul SA, Won H, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. 2018;554:189-194. doi:10.1038/nature25475
  10. Thuss-Patience PC, Shah MA, Ohtsu A, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): An international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18:640-653. doi:10.1016/S1470-2045(17)30111-0
  11. Makiyama A, Sagara K, Kawada J, et al. A Randomized phase II study of weekly paclitaxel ± trastuzumab in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer refractory to trastuzumab combined with fluoropyrimidine and platinum: WJOG7112G (T-ACT). J Clin Oncol. 2018;36(15_suppl):4011. doi:10.1200/JCO.2018.36.15_suppl.4011
  12. Catenacci DVT, Park H, Lockhart AC, Gold PJ. Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA) J Clin Oncol. 2018;36(4_suppl):140. doi:10.1200/JCO.2018.36.4_suppl.140
  13. Catenacci DVT, Kang YK, Park H, et al. Margetuximab plus pembrolizumab in patients with previously treated HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): A single-arm, phase 1b-2 trial. Lancet Oncol. 2020;21:1066-1076. doi:10.1016/S1470-2045(20)30326-0Rha S, Kim CG, Jung M, et al. Multicenter phase 1b/II study of second-line trastuzumab, ramucirumab, and paclitaxel in patients with HER2-positive advanced gastric or gastroesophageal junction cancer. Updated HER-RAM study with biomarker analysis. J Clin Oncol. 2022;40(4_suppl):330. doi:10.1200/JCO.2022.40.4_suppl.330
  14. Xu J,Ying R, Wu J, et al. KN026 (anti-HER2 bispecific antibody) in patients with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancer. Eur J Cancer. 2023;178:1-12. doi:10.1016/j.ejca.2022.10.004
  15. Jeong H, Jeong JH, Kim KP, et al. Feasibility of HER2-targeted therapy in advanced biliary tract cancer: A prospective pilot sudy of trastuzumab biosimilar in combination with gemcitabine plus cisplatin. Cancers (Basel). 2021;13:161. doi:10.3390/cancers13020161
  16. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2024;42:47-58. doi:10.1200/JCO.23.02005
  17. Javle MM, Oh DY, Ikeda M, et al. Varlitinib plus capecitabine in second-line advanced biliary tract cancer: A randomized, phase II study (TreeTopp). ESMO Open. 2022;7:100314. doi:10.1016/j.esmoop.2021.100314
  18. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): A multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol.2021;22:1290-1300. doi:10.1016/S1470-2045(21)00336-3
  19. Harding JJ, Piha-Paul SA, Shah RH, et al. Targeting HER2 mutation–positive advanced biliary tract cancers with neratinib: Final results from the phase 2 SUMMIT basket trial. J Clin Oncol. 2022;40(16_suppl):4079. doi:10.1200/JCO.2022.40.16_suppl.4079
  20. Ohba A, Morizane C, Kawamoto Y, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): An investigator-initiated multicenter phase 2 study (HERB trial). J Clin Oncol. 2022;40(16_suppl):4006. doi:10.1200/JCO.2022.40.16_suppl.4006
  21. Nakamura Y, Mizuno N, Sunakawa Y, et al. Tucatinib and trastuzumab for previously treated human epidermal growth factor receptor 2-positive metastatic biliary tract cancer (SGNTUC-019): A phase II basket study. J Clin Oncol. 2023;41:5569-5578. doi:10.1200/JCO.23.00606
  22. Pant S, Fan J, Oh DY, et al. Results from the pivotal phase (Ph) 2b HERIZON-BTC-01 study: Zanidatamab in previously-treated HER2-amplified biliary tract cancer (BTC). J Clin Oncol. 2023;41(16_suppl):4008. doi:10.1200/JCO.2023.41.16_suppl.4008

All URLs accessed April 12, 2025

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