Gastric and Esophageal Cancers: Guidelines Updates

Presented by:
Crystal S. Denlinger
Search for other papers by Crystal S. Denlinger in
Current site
Google Scholar
PubMed
Close
 MD
,
Kristina A. Matkowskyj
Search for other papers by Kristina A. Matkowskyj in
Current site
Google Scholar
PubMed
Close
 MD, PhD
, and
Mary F. Mulcahy
Search for other papers by Mary F. Mulcahy in
Current site
Google Scholar
PubMed
Close
 MD
Restricted access

For the treatment of gastric and esophageal cancers, several pivotal trials—especially those evaluating immune checkpoint inhibitors (ICIs)—have altered the treatment landscape and led to changes in the NCCN Guidelines. In addition to pembrolizumab and nivolumab, new treatment options include trastuzumab-deruxtecan (T-DXd), ramucirumab, and trifluridine/tipiracil. These agents convey varying degrees of benefit depending on treatment line, PD-L1 expression, HER2 expression, and tumor histology. Recently, ICIs have been incorporated into the first-line treatment of HER2-negative advanced esophageal, gastroesophageal junction (GEJ), and gastric cancers, in addition to second-line treatment of advanced esophageal and GEJ cancer of squamous histology. T-DXd is another new second-line option for HER2-positive esophageal, GEJ, and gastric adenocarcinomas. ICIs are now moving into the adjuvant setting as well, and a new recommendation is nivolumab use after preoperative chemoradiation and surgery in patients who have residual disease identified at the time of their R0 resections.

Disclosures: Dr. Denlinger has disclosed serving as a scientific advisor for BeiGene, Bristol Myers Squibb Company, Exelixis Inc., Merck & Co., Inc., and Zymeworks Inc.; and receiving honoraria from Eli Lilly and Company and Taiho Pharmaceuticals Co., Ltd. Dr. Matkowskyj has disclosed receiving consulting fees from Elephas Bio and McDowell & Morrissette Professional Association. Dr. Mulcahy has disclosed no relevant financial relationships.

Correspondence: Crystal S. Denlinger, MD, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. Email: crystal.denlinger@fccc.edu;
Kristina A. Matkowskyj, MD, PhD, University of Wisconsin Carbone Cancer Center, 600 Highland Avenue, L5/183 CSC, Madison, WI 53792. Email: matkowskyj@wisc.edu; and
Mary F. Mulcahy, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 676 North St. Clair Street, Suite 850, Chicago, IL 60611. Email: mmulcahy@nm.org
  • Collapse
  • Expand
  • 1.

    Moehler M, Shitara K, Garrido M, et al. Nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: first results of the CheckMate 649 study [abstract]. Ann Oncol 2020;31(Suppl 4):S1191. Abstract LBA6_PR.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Shitara K, Van Cutsem E, Bang Y, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial. JAMA Oncol 2020;6:15711580.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Boku N, Ryu MH, Kato K, et al. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4). Ann Oncol 2019;30:250258.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Boku N, Ryu MH, Oh D, et al. Nivolumab plus chemotherapy versus chemotherapy alone in patients with previously untreated advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer: ATTRACTION-4 (ONO-4538-37) study [abstract]. Ann Oncol 2020;31(Suppl 4): Abstract LBA7_PR.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Kato K, Sun JM, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: the phase 3 KEYNOTE-590 study. Ann Oncol 2020;31(Suppl 4):S1192.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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;21:20392049.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    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;18:640653.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    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) [abstract]. J Clin Oncol 2018;36(Suppl):Abstract 4011.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020;382:24192430.

  • 10.

    Fuchs CS, Shitara K, Di Bartolomeo M, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Oncol 2019;20:420435.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Lorenzen S, Thuss-Patience PC, Pauligk C, et al. FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel: results from the phase II RAMIRIS study of the AIO [abstract]. J Clin Oncol 2020;38(Suppl):Abstract 4514.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Shitara K, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 2018;392:123133.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Fuchs CS, Toshihiko D, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol 2018;4:e180013.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Chao J, Fuchs CS, Shitara K, et al. Pembrolizumab (pembro) in microsatellite instability-high (MSI-H) advanced gastric/gastroesophageal junction cancer G/GEJ) by line of therapy [abstract]. J Clin Oncol 2020;38(Suppl):Abstract 430.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Chao J, Fuchs CS, Shitara K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials [published online April 1, 2021]. JAMA Oncol, doi: 10.1001/jamaoncol 2021;0275

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Shitara K, Özgüroğlu M, Bang YJ, et al. The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061 [abstract]. J Clin Oncol 2020;38(Suppl):Abstract 4537.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018;19:14371448.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Kelly, RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiation therapy (CRT): first results of the CheckMate 577 study [abstract]. Ann Oncol 2020;31:s11931194. Abstract LBA9_PR.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Smyth EC, Cervantes E, Addition of nivolumab to chemotherapy in patients with advanced gastric cancer: a relevant step ahead, but still many questions to answer. ESMO Open 2020;5:e001107.

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 5560 1006 162
PDF Downloads 3792 375 37
EPUB Downloads 0 0 0