Gastric cancer

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There is significant overlap between regimens for gastric cancer and esophageal cancer, if you can't find the regimen you're looking for here, please try the esophageal cancer page.

21 regimens on this page
26 variants on this page

Contents


Guidelines

CAP/ASCP/ASCO

ESMO

ESMO/ESSO/ESTRO

NCCN

Neoadjuvant chemotherapy

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study Evidence Comparator Efficacy
Cunningham et al. 2006 (MAGIC) Phase III Surgery alone Superior OS

This is the neoadjuvant portion of pre-planned "perioperative" therapy.

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

Surgical resection is performed 3 to 6 weeks after the completion of cycle 3, followed in 6 to 12 weeks by adjuvant ECF.

References

  1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed

FLOT

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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)

Regimen

Study Evidence Comparator Efficacy
Al-Batran et al. 2017 (FLOT4-AIO) Phase III See link See link

This is the neoadjuvant portion of pre-planned perioperative chemotherapy.

Chemotherapy

14-day cycle for 4 cycles

Treatment followed by surgery and adjuvant FLOT.

References

  1. Abstract: Salah-Eddin Al-Batran, Nils Homann, Harald Schmalenberg, Hans-Georg Kopp, Georg Martin Haag, Kim Barbara Luley, Wolff H. Schmiegel, Gunnar Folprecht, Stephan Probst, Nicole Prasnikar, Peter C. Thuss-Patience, Wolfgang Fischbach, Jorg Trojan, Michael Koenigsmann, Claudia Pauligk, Thorsten Oliver Goetze, Elke Jaeger, Johannes Meiler, Martin H. Schuler, and Ralf Hofheinz. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. Journal of Clinical Oncology 2017 35:15_suppl, 4004-4004 link to abstract

Cisplatin & Fluorouracil

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Regimen

Study Evidence Comparator Efficacy
Ychou et al. 2011 Phase III Surgery alone Seems to have superior OS

This is the neoadjuvant portion of pre-planned "perioperative" therapy.

Chemotherapy

28-day cycle for 2 to 3 cycles

Treatment followed by surgical resection, then adjuvant cisplatin & 5-FU.

References

  1. Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. link to original article contains protocol PubMed

Adjuvant therapy

5-FU & Leucovorin, then 5-FU, Leucovorin, RT, then 5-FU & Leucovorin

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Macdonald et al. 2001 Phase III Surgery alone Superior OS

Treatment is to start 20 to 40 days after surgery.

Chemotherapy, part 1

28-day cycle for 1 cycle, followed by:

Chemoradiotherapy

  • Fluorouracil (5-FU) 400mg/m2 IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
  • Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
  • Concurrent radiation therapy starting on day 1 with 180 cGy, 5 days per week; 25 fractions given over 5 weeks for a total of 4500 cGy

35-day course, followed by:

Chemotherapy, part 2

28-day cycle for 2 cycles

References

  1. 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 contains protocol PubMed

Cisplatin & Fluorouracil

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Regimen

Study Evidence Comparator Efficacy
Ychou et al. 2011 Phase III Surgery alone Seems to have superior OS

This is the adjuvant portion of pre-planned "perioperative" therapy.

Preceding treatment

Chemotherapy

28-day cycle for 3 to 4 cycles, for a total of 6 cycles

References

  1. Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. link to original article contains protocol PubMed

CX

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CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Lee et al. 2011 (ARTIST) Phase III XP, then RT, then XP Might have inferior DFS

Chemotherapy

21-day cycle for 6 cycles

References

  1. Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. link to original article contains verified protocol PubMed
    1. Update: Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. link to original article PubMed

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study Evidence Comparator Efficacy
Cunningham et al. 2006 (MAGIC) Phase III Surgery alone Superior OS

This is the adjuvant portion of pre-planned "perioperative" therapy.

Preceding treatment

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

References

  1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed

FLOT

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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)

Regimen

Study Evidence Comparator Efficacy
Al-Batran et al. 2017 (FLOT4-AIO) Phase III See link See link

This is the adjuvant portion of pre-planned perioperative chemotherapy.

Preceding treatment

Chemotherapy

14-day cycle for 4 cycles

References

  1. Abstract: Salah-Eddin Al-Batran, Nils Homann, Harald Schmalenberg, Hans-Georg Kopp, Georg Martin Haag, Kim Barbara Luley, Wolff H. Schmiegel, Gunnar Folprecht, Stephan Probst, Nicole Prasnikar, Peter C. Thuss-Patience, Wolfgang Fischbach, Jorg Trojan, Michael Koenigsmann, Claudia Pauligk, Thorsten Oliver Goetze, Elke Jaeger, Johannes Meiler, Martin H. Schuler, and Ralf Hofheinz. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. Journal of Clinical Oncology 2017 35:15_suppl, 4004-4004 link to abstract

Observation

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Regimen

Study Evidence Comparator Efficacy
Sakuramoto et al. 2007 (ACTS-GC) Phase III S-1 Inferior OS

No further treatment after surgery.

Preceding treatment

  • R0 gastrectomy with at least D2 dissection

References

  1. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains verified protocol PubMed
    1. Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed

S-1 monotherapy

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Regimen

Study Evidence Comparator Efficacy
Sakuramoto et al. 2007 (ACTS-GC) Phase III Observation Superior OS

Preceding treatment

  • R0 gastrectomy with at least D2 dissection, within 6 weeks

Chemotherapy

  • Tegafur, gimeracil, oteracil (S-1) as follows:
    • BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
    • BSA between 1.25 and 1.5 m2: 50 mg PO BID on days 1 to 28
    • BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28

42-day cycles for one year

References

  1. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains verified protocol PubMed
    1. Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed
  2. Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. link to original article PubMed

Metastatic or locally advanced disease, first-line

Cisplatin & S-1

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Regimen

Study Evidence Comparator Efficacy
Koizumi et al. 2008 (SPIRITS) Phase III (E) S-1 Seems to have superior OS
Fujitani et al. 2016 (REGATTA) Non-randomized portion of RCT

Note: in REGATTA, there was no difference in outcome amongst patients who did or did not undergo surgery.

Preceding treatment

  • REGATTA: Gastrectomy with D1 lymphadenectomy versus no surgery

Chemotherapy

35-day cycles

References

  1. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. link to SD article contains verified protocol PubMed
  2. Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. link to SD article contains verified protocol PubMed

CX

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CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Kang et al. 2009 Phase III Cisplatin & Fluorouracil Non-inferior PFS
Ohtsu et al. 2011 (AVAGAST) Phase III (C) Capecitabine, Cetuximab, Bevacizumab Seems not superior
Lordick et al. 2013 (EXPAND) Phase III (C) Capecitabine, Cisplatin, Cetuximab Seems not superior
Kim et al. 2014 Phase III (C) Capecitabine, Cisplatin, Simvastatin Seems not superior

Chemotherapy

Supportive medications

21-day cycles, varied duration (see below)

Subsequent treatment

References

  1. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains verified protocol PubMed content property of HemOnc.org
  2. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
  3. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed
  4. Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains verified protocol PubMed

CX & Trastuzumab

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CX: Cisplatin, Xeloda (Capecitabine)

Regimen #1

Study Evidence Comparator Efficacy
Shah et al. 2017 (HELOISE) Phase IIIb CX & HD-Trastuzumab Seems not superior

Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridisation.

Chemotherapy

21-day cycle for up to 6 cycles; trastuzumab alone continued until progression of disease or unacceptable toxicity

Regimen #2

Study Evidence Comparator Efficacy
Bang et al. 2010 (ToGA) Phase III CX Superior OS

Patients had overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

21-day cycles

References

  1. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. 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. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
  2. Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. 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 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.link to original article contains verified protocol PubMed

ECC

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ECC: Epirubicin, Cisplatin, Capecitabine
ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)

Regimen #1, continuous capecitabine

Study Evidence Comparator Efficacy
Catenacci et al. 2017 (RILOMET-1) Randomized Phase II ECX & Rilotumumab Superior OS

Patients had unresectable or metastatic MET-positive gastric or gastro-esophageal junction cancer.

Chemotherapy

21-day cycle for up to 10 cycles

Regimen #2, intermittent capecitabine

Study Evidence Comparator Efficacy
Konings et al. 2010 Randomized Phase II ECC+P Seems not superior

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. link to original article contains verified protocol PubMed
  2. Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. link to original article contains verified protocol PubMed

Irinotecan monotherapy

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Regimen

Study Evidence
Enzinger et al. 2005 Phase II

Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."

Chemotherapy

42-day cycles

References

  1. Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. link to original article PubMed

Maintenance after first-line therapy

Capecitabine monotherapy

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Regimen

Study Evidence
Ohtsu et al. 2011 (AVAGAST) Non-randomized portion of RCT
Kim et al. 2014 Non-randomized portion of RCT

Preceding treatment

  • AVAGAST: CX x 6
  • Kim et al. 2014: CX x 8

Chemotherapy

21-day cycles

References

  1. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
  2. Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains verified protocol PubMed

Metastatic or locally advanced disease, subsequent lines of therapy

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Thuss-Patience et al. 2011 Phase III Irinotecan Seems to have inferior OS
Kang et al. 2012 Phase III Docetaxel
Irinotecan
Inferior OS

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

  1. Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
  2. Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed

Docetaxel monotherapy

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Regimen #1, 60 mg/m2

Study Evidence Comparator Efficacy
Kang et al. 2012 Phase III (E) Best supportive care Superior OS

Chemotherapy

21-day cycles

Regimen #2, 75 mg/m2

Study Evidence Comparator Efficacy
Thuss-Patience et al. 2017 (GATSBY) Phase III (C) T-DM1 Seems not superior

Patients had HER2-positive disease.

Chemotherapy

21-day cycles

References

  1. Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article contains protocol PubMed
  2. Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. 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 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains protocol PubMed

Irinotecan monotherapy

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Regimen #1, q3wk dosing

Study Evidence Comparator Efficacy
Thuss-Patience et al. 2011 Phase III (E) Best supportive care Seems to have superior OS

Chemotherapy

  • Irinotecan (Camptosar) as follows:
    • Cycle 1: 250 mg/m2 (maximum dose of 500 mg) IV over 30 minutes once on day 1
    • Cycles 2 to 10 (depending on toxicity): 350 mg/m2 IV over 30 minutes once on day 1

Supportive medications

21-day cycle for up to 10 cycles

Regimen #2, alternate q3wk dosing

Study Evidence Comparator
Roy et al. 2013 Randomized Phase II Docetaxel
Irinotecan liposome

Chemotherapy

21-day cycles

Regimen #3, q2wk dosing

Study Evidence Comparator Efficacy
Kang et al. 2012 Phase III (E) Best supportive care Superior OS

Chemotherapy

14-day cycles

Regimen #4, 4 weeks out of 6

Study Evidence
Enzinger et al. 2005 Phase II

Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."

Chemotherapy

  • Irinotecan (Camptosar) 125 mg/m2 IV over 60 minutes (Mühr-Wilkenshoff et al. 2003) or 90 minutes (Enzinger et al. 2005) once per day on days 1, 8, 15, 22

42-day cycles

References

  1. Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
  2. Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
  3. Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article PubMed

Nivolumab monotherapy

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Regimen

Study Evidence Comparator Efficacy
Kang et al. 2017 (ATTRACTION-2) Phase III Placebo Superior OS

Immunotherapy

14-day cycles

References

  1. 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 contains verified protocol PubMed

Paclitaxel monotherapy

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Regimen #1, weekly

Study Evidence Comparator Efficacy
Thuss-Patience et al. 2017 (GATSBY) Phase III (C) T-DM1 Seems not superior

Patients had HER2-positive disease.

Chemotherapy

Continued until progression

Regimen #2, 3 out of 4 weeks

Study Evidence Comparator Efficacy
Wilke et al. 2014 (RAINBOW) Phase III Ramucirumab & Paclitaxel Seems to have inferior OS

Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."

Chemotherapy

28-day cycles

References

  1. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed
  2. Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. 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 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains protocol PubMed
  3. Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. link to original article PubMed

Pembrolizumab monotherapy

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Regimen

Study Evidence ORR
Fuchs et al. 2017 (KEYNOTE-059) Phase II 11% (95% CI 8-16)

Immunotherapy

21-day cycle for up to 2 years or disease progression

References

  1. Abstract: Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, ...Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Philippe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V.T. Catenacci, Yung-Jue Bang, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Harry H. Yoon (2017). KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4003-4003. link to abstract

Placebo

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Regimen

Study Evidence Comparator Efficacy
Fuchs et al. 2013 (REGARD) Phase III (C) Ramucirumab Seems to have inferior OS
Pavlakis et al. 2016 (INTEGRATE) Randomized Phase II (C) Regorafenib Inferior PFS
Kang et al. 2017 (ATTRACTION-2) Randomized Phase II (C) Nivolumab Inferior OS

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."

No active antineoplastic treatment.

References

  1. 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 contains verified protocol PubMed
  2. Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains verified protocol link to PMC article PubMed
  3. 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 contains verified protocol PubMed

Ramucirumab monotherapy

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Regimen

Study Evidence ORR Comparator Comparator ORR Efficacy Pt Population
Fuchs et al. 2013 (REGARD) Phase III (E) 3% Placebo 3% Seems to have superior OS Chemo exposed

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."

Chemotherapy

Given until progression of disease, unacceptable toxicity, or death

References

  1. 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 contains verified protocol PubMed

Ramucirumab & Paclitaxel

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Regimen

Study Evidence ORR Comparator Comparator ORR Efficacy Pt Population
Wilke et al. 2014 (RAINBOW) Phase III (E) 28% (95% CI 23-33%) Paclitaxel 16% (95% CI 13-20%) Seems to have superior OS Chemo exposed

Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."

Chemotherapy

28-day cycles

References

  1. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed

Regorafenib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Pavlakis et al. 2016 (INTEGRATE) Randomized Phase II (E) Placebo Superior PFS

Chemotherapy

28-day cycles

References

  1. Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains verified protocol link to PMC article PubMed