Esophageal adenocarcinoma - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main esophageal adenocarcinoma page for regimens that include active anticancer treatment.


Neoadjuvant induction therapy

No neoadjuvant therapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Walsh et al. 1996 1990-1995 Randomized Phase 2 (C) CF & RT Inferior OS

Surgery as primary therapy; i.e., no induction chemotherapy or chemoradiotherapy, and no adjuvant therapy.

Subsequent treatment

References

  1. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. link to original article PubMed

Adjuvant therapy

Observation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Macdonald et al. 2001 (INT-0116) 1991-1998 Phase 3 (C) FULV & RT Inferior OS

Surgery as primary therapy; i.e., no induction chemotherapy or chemoradiotherapy, and no adjuvant therapy.

McDonald et al. patients: 100% adenocarcinoma histology, originating from the stomach or gastroesophageal junction.

Preceding treatment

References

  1. INT-0116: Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. link to original article PubMed

Metastatic or locally advanced disease, subsequent lines of therapy

Best supportive care

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ford et al. 2013 (COUGAR-02) 2008-2012 Phase 3 (C) Docetaxel Inferior OS

COUGAR-02 patients: 100% adenocarcinoma histology (20% esophageal, 35% gastroesophageal junction, 45% stomach) that progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination. 15% ECOG PS of 2. 12% locally advanced, 88% metastatic disease. Supportive care only.

References

  1. COUGAR-02: Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. link to original article PubMed NCT00978549

Placebo

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fuchs et al. 2013 (REGARD) 2009-2012 Phase 3 (C) Ramucirumab Seems to have inferior OS
Li et al. 2016 2011-01 to 2012-11 Phase 3 (C) Apatinib Inferior OS
Kang et al. 2017 (ATTRACTION-2) 2014-2016 Phase 3 (C) Nivolumab Inferior OS

Note: Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment." COG is renamed as COG-esoph so as not to confuse with the Children's Oncology Group.

No active antineoplastic treatment.

REGARD patients: 100% adenocarcinoma histology (25% gastroesophageal junction, 75% gastric origin).

Li et al. 2016 patients: 100% adenocarcinoma histology (70% gastric origin, 22% gastroesophageal junction, 8% unknown). All patients with at least two prior lines of treatment.

ATTRACTION-2 patients: 100% adenocarcinoma. Patients had progression on two prior lines of systemic treatment.

References

  1. REGARD: Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. link to original article PubMed NCT00917384
  2. Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016 May 1;34(13):1448-54. Epub 2016 Feb 16. link to original article PubMed
  3. ATTRACTION-2: Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. link to original article PubMed NCT02267343
    1. Subgroup analysis: Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Nakajima TE, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer. 2019 Mar;22(2):344-354. Epub 2018 Dec 1. link to original article link to original article PubMed
  4. INTEGRATE IIa: NCT02773524
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