Stomach cancer
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
localised: suitable for surgery
surgery
Multi-disciplinary evaluation is strongly encouraged before therapy is started.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 [27]Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):1005-20. https://www.annalsofoncology.org/article/S0923-7534(22)01851-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35914639?tool=bestpractice.com
Surgery is the primary treatment option for patients with localised (T1b-T2, N0) gastric cancer, with a goal of complete resection with negative margins.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 [27]Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):1005-20. https://www.annalsofoncology.org/article/S0923-7534(22)01851-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35914639?tool=bestpractice.com Patients with carcinoma in situ (Tis) or T1a tumours may be candidates for endoscopic therapies.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
The aim is complete resection of the primary tumour with negative margins.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Subtotal gastrectomy is the preferred approach for distal gastric cancer.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Patients undergoing total gastrectomy for distal gastric cancers have no survival benefit compared with those undergoing subtotal gastrectomy.[34]Bozzetti F, Marubini E, Bonfanti G, et al. Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg. 1999 Aug;230(2):170-8. http://www.ncbi.nlm.nih.gov/pubmed/10450730?tool=bestpractice.com [35]Gouzi JL, Huguier M, Fagniez PL, et al. Total versus subtotal gastrectomy for adenocarcinoma of the gastric antrum. A French prospective controlled study. Ann Surg. 1989 Feb;209(2):162-6. http://www.ncbi.nlm.nih.gov/pubmed/2644898?tool=bestpractice.com Proximal gastrectomy or total gastrectomy is usually recommended for patients with proximal tumours.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
The American Society for Gastrointestinal Endoscopy (ASGE) suggests surgery over endoscopic approaches for lesions that are poorly differentiated and of any size; however, surgery is not recommended in early-stage lesions that are well- or moderately differentiated, intestinal type, and measure ≤3 cm.[36]ASGE standards of practice committee, Forbes N, Elhanafi SE, et al. American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: summary and recommendations. Gastrointest Endosc. 2023 Sep;98(3):271-84. https://www.giejournal.org/article/S0016-5107(23)00355-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/37498266?tool=bestpractice.com
Patients with superficial early gastric cancer (T1a) can be treated with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD).[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Appropriate candidates for EMR are those with adenocarcinoma confined to the mucosa, <2 cm in diameter, low or moderate degree of differentiation, without evidence of ulcer, and with no lymphovascular involvement.[37]Bennett C, Wang Y, Pan T. Endoscopic mucosal resection for early gastric cancer. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD004276. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004276.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/19821324?tool=bestpractice.com [38]Takekoshi T, Baba Y, Ota H, et al. Endoscopic resection of early gastric carcinoma; results of a retrospective analysis of 308 cases. Endoscopy. 1994 May;26(4):352-8. http://www.ncbi.nlm.nih.gov/pubmed/8076567?tool=bestpractice.com [39]Soetikno R, Kaltenbach T, Yeh R, et al. Endoscopic mucosal resection for early cancers of the upper gastrointestinal tract. J Clin Oncol. 2005 Jul 10;23(20):4490-8. http://www.ncbi.nlm.nih.gov/pubmed/16002839?tool=bestpractice.com
The factors to consider while choosing between ESD and EMR as per ASGE include differentiation (well or moderate vs. poor), morphology (ulcerated vs. non-ulcerated), type of cancer (intestinal vs. diffuse), and size.[36]ASGE standards of practice committee, Forbes N, Elhanafi SE, et al. American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: summary and recommendations. Gastrointest Endosc. 2023 Sep;98(3):271-84. https://www.giejournal.org/article/S0016-5107(23)00355-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/37498266?tool=bestpractice.com Either ESD or EMR can be used in early-stage, well- or moderately differentiated, non-ulcerated, intestinal type gastric cancers measuring <20 mm, while ESD is preferred over EMR in well- or moderately differentiated lesions measuring 20-30 mm, with or without ulceration.[36]ASGE standards of practice committee, Forbes N, Elhanafi SE, et al. American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: summary and recommendations. Gastrointest Endosc. 2023 Sep;98(3):271-84. https://www.giejournal.org/article/S0016-5107(23)00355-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/37498266?tool=bestpractice.com
Extent of lymph node dissection is controversial. Studies have failed to show survival benefit between D1 dissection (dissection of the perigastric nodes) and D2 dissection (dissection of perigastric nodes and nodes along the left gastric, hepatic, coeliac, and splenic arteries). D2 dissection may be associated with lower rates of locoregional recurrence and gastric cancer-related death, but may also be associated with higher rates of morbidity and mortality. A modified (spleen-preserving) D2 dissection is considered a standard at many institutions. The addition of para-aortic dissection to D2 dissection does not improve survival.[40]Cushieri A, Fayers P, Fielding J, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet. 1996 Apr 13;347(9007):995-9.
http://www.ncbi.nlm.nih.gov/pubmed/8606613?tool=bestpractice.com
[41]Songun I, Putter H, Kranenbarg EM, et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010 May;11(5):439-49.
http://www.ncbi.nlm.nih.gov/pubmed/20409751?tool=bestpractice.com
[42]Sasako M, Sano T, Yamamoto S, et al; Japan Clinical Oncology Group. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008 Jul 31;359(5):453-62.
https://www.nejm.org/doi/full/10.1056/NEJMoa0707035
http://www.ncbi.nlm.nih.gov/pubmed/18669424?tool=bestpractice.com
[ ]
In people with adenocarcinoma of the stomach, how do different types of lymph node dissection affect outcomes?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.954/fullShow me the answer
Short-term outcomes from randomised controlled trials suggest that laparoscopic gastrectomy for clinical stage 1 gastric cancer is safe and has the benefit of lower occurrence of wound complication compared with conventional open gastrectomy, although evidence is low quality.[43]Ohtani H, Tamamori Y, Noguchi K, et al. A meta-analysis of randomized controlled trials that compared laparoscopy-assisted and open distal gastrectomy for early gastric cancer. J Gastrointest Surg. 2010 Jun;14(6):958-64.
http://www.ncbi.nlm.nih.gov/pubmed/20354807?tool=bestpractice.com
[44]Kim W, Kim HH, Han SU, et al; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group. Decreased morbidity of laparoscopic distal gastrectomy compared with open distal gastrectomy for stage I gastric cancer: short-term outcomes from a multicenter randomized controlled trial (KLASS-01). Ann Surg. 2016 Jan;263(1):28-35.
http://www.ncbi.nlm.nih.gov/pubmed/26352529?tool=bestpractice.com
[45]Kim HH, Han SU, Kim MC, et al. Effect of laparoscopic distal gastrectomy vs open distal gastrectomy on long-term survival among patients with stage I gastric cancer: the KLASS-01 randomized clinical trial. JAMA Oncol. 2019 Apr 1;5(4):506-13.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2723581
http://www.ncbi.nlm.nih.gov/pubmed/30730546?tool=bestpractice.com
[ ]
How does laparoscopic compare with open gastrectomy at improving outcomes in people with gastric cancer?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1485/fullShow me the answer Other studies show no difference in short-term mortality between laparoscopic and open gastrectomy and no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy, based on low-quality evidence.[46]Best LM, Mughal M, Gurusamy KS. Laparoscopic versus open gastrectomy for gastric cancer. Cochrane Database Syst Rev. 2016 Mar 31;(3):CD011389.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011389.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/27030300?tool=bestpractice.com
perioperative or postoperative chemotherapy
Additional treatment recommended for SOME patients in selected patient group
Patients with more advanced disease (T2 or higher, and any N) should be offered perioperative chemotherapy in addition to gastrectomy.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 [27]Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):1005-20. https://www.annalsofoncology.org/article/S0923-7534(22)01851-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35914639?tool=bestpractice.com Perioperative chemotherapy has been shown to improve overall survival in patients with stage 2 or higher disease, compared with surgery alone.[53]Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. https://www.nejm.org/doi/full/10.1056/NEJMoa055531 http://www.ncbi.nlm.nih.gov/pubmed/16822992?tool=bestpractice.com [54]Sun P, Xiang JB, Chen ZY. Meta-analysis of adjuvant chemotherapy after radical surgery for advanced gastric cancer. Br J Surg. 2009 Jan;96(1):26-33. http://www.ncbi.nlm.nih.gov/pubmed/19016271?tool=bestpractice.com The preferred regimen for most patients with good-to-moderate performance status is FLOT (fluorouracil, folinic acid, oxaliplatin, docetaxel).[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Fluorouracil plus cisplatin is an alternative regimen.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 FLOT is associated with better outcomes in patients with resectable gastric and gastro-oesophageal junction cancer treatment compared with other regimens.[55]ClinicalTrials.gov. 5-FU, leucovorin, oxaliplatin and docetaxel (FLOT) versus epirubicin, cisplatin and 5-FU (ECF) in patients with locally advanced, resectable gastric cancer. NCT01216644. Jun 2019 [internet publication]. https://clinicaltrials.gov/ct2/show/NCT01216644
Postoperative chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin is indicated for patients who have undergone gastrectomy with primary D2 lymph node dissection.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
Folinic acid is indicated with certain fluorouracil-based regimens. Depending on availability, the regimens may be used with or without folinic acid.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocols for dosing guidelines.
Primary options
Perioperative chemotherapy
fluorouracil
and
folinic acid
and
oxaliplatin
and
docetaxel
OR
Perioperative chemotherapy
fluorouracil
and
cisplatin
OR
Postoperative chemotherapy
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
postoperative chemoradiotherapy
Additional treatment recommended for SOME patients in selected patient group
Postoperative chemoradiotherapy is recommended for patients who have undergone gastrectomy with limited (D0 or D1) lymph node dissection. Postoperative chemoradiotherapy is associated with a significantly lower local recurrence rate in this group of patients, compared with surgery alone.[47]Dikken JL, Jansen EP, Cats A, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol. 2010 May 10;28(14):2430-6. https://ascopubs.org/doi/10.1200/JCO.2009.26.9654 http://www.ncbi.nlm.nih.gov/pubmed/20368551?tool=bestpractice.com [48]Macdonald JS, Smalley SR, Benedetti J, et al. 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. https://www.nejm.org/doi/10.1056/NEJMoa010187 http://www.ncbi.nlm.nih.gov/pubmed/11547741?tool=bestpractice.com [49]Smalley SR, Benedetti JK, Haller DG, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. http://www.ncbi.nlm.nih.gov/pubmed/22585691?tool=bestpractice.com The preferred regimen is radiotherapy and fluorouracil or capecitabine.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
Postoperative chemoradiotherapy has not been shown to reduce local recurrence rates in patients who have undergone gastrectomy with D2 lymph node dissection; these patients should be offered postoperative chemotherapy instead.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 [47]Dikken JL, Jansen EP, Cats A, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol. 2010 May 10;28(14):2430-6. https://ascopubs.org/doi/10.1200/JCO.2009.26.9654 http://www.ncbi.nlm.nih.gov/pubmed/20368551?tool=bestpractice.com [50]Park SH, Lim DH, Sohn TS, et al; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-74. https://www.annalsofoncology.org/article/S0923-7534(20)43172-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/33278599?tool=bestpractice.com
Adverse effects of radiotherapy include nausea, vomiting (patients may need to be pre-treated with anti-emetics prior to radiation), weight loss, and diarrhoea. Less commonly, radiation can cause small bowel obstruction, liver damage, and kidney damage.
Folinic acid is indicated with certain fluorouracil-based regimens. Depending on availability, the regimens may be used with or without folinic acid.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocols for dosing guidelines.
Primary options
fluorouracil
OR
capecitabine
localised: not suitable for surgery
chemoradiotherapy
Patients with localised disease who are not surgical candidates should be offered chemoradiotherapy. The preferred regimens consist of radiotherapy and fluorouracil plus oxaliplatin or cisplatin.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Other recommended regimens include a fluoropyrimidine (fluorouracil or capecitabine) plus paclitaxel.
Overall survival is higher in patients with locally advanced gastric cancer treated with chemoradiotherapy than in patients treated with radiotherapy alone.[51]Moertel CG, Childs DS, Reitemeier RJ, et al. Combined 5-fluorouracil and supervoltage radiation therapy for locally advanced and metastatic gastric carcinoma. Lancet. 1969 Oct 25;2(7626):865-7. http://www.ncbi.nlm.nih.gov/pubmed/4186452?tool=bestpractice.com [52]Le Chevalier T, Smith FP, Harter WK, et al. Chemotherapy and combined modality therapy for locally advanced and metastatic gastric carcinoma. Semin Oncol. 1985 Mar;12(1):46-53. http://www.ncbi.nlm.nih.gov/pubmed/3883501?tool=bestpractice.com
Adverse effects of radiation include nausea, vomiting (patients may need to be pre-treated with anti-emetics prior to radiation), weight loss, and diarrhoea. Less commonly, radiation can cause small bowel obstruction, liver damage, and kidney damage.
Folinic acid is indicated with certain fluorouracil-based regimens. Depending on availability, the regimens may be used with or without folinic acid.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocols for dosing guidelines.
Primary options
fluorouracil
-- AND --
oxaliplatin
or
cisplatin
OR
fluorouracil
or
capecitabine
-- AND --
paclitaxel
advanced and metastatic disease
chemotherapy and/or immunotherapy
Chemotherapy improves quality of life and survival when compared with best supportive care in patients with metastatic gastric cancer.[56]Glimelius B, Ekström K, Hoffman K, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997 Feb;8(2):163-8.
http://www.ncbi.nlm.nih.gov/pubmed/9093725?tool=bestpractice.com
[57]Wagner AD, Syn NL, Moehler M, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017 Aug 29;(8):CD004064.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004064.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/28850174?tool=bestpractice.com
[58]Pyrhönen S, Kuitunen T. Nyandoto P, et al. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer. 1995 Mar;71(3):587-91.
http://www.ncbi.nlm.nih.gov/pubmed/7533517?tool=bestpractice.com
[ ]
Does randomized controlled trial evidence support the use of chemotherapy in people with advanced gastric cancer?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1917/fullShow me the answer Immunotherapy plus chemotherapy is associated with improved survival, compared with chemotherapy alone, in patients with metastatic gastric cancer.[59]Bang YJ, Van CE, Feyereislova A, et al; 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.
http://www.ncbi.nlm.nih.gov/pubmed/20728210?tool=bestpractice.com
[60]ClinicalTrials.gov. Efficacy study of nivolumab plus ipilimumab or nivolumab plus chemotherapy against chemotherapy in stomach cancer or stomach/esophagus junction cancer (CheckMate649). NCT02872116. Jun 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT02872116
[61]Kelly RJ, Ajani JA, Kuzdzal J, et al; CheckMate 577 Investigators. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021 Apr 1;384(13):1191-203.
https://www.nejm.org/doi/10.1056/NEJMoa2032125
http://www.ncbi.nlm.nih.gov/pubmed/33789008?tool=bestpractice.com
[62]Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436782
http://www.ncbi.nlm.nih.gov/pubmed/34102137?tool=bestpractice.com
[63]Kang YK, Chen LT, Ryu MH, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-47.
http://www.ncbi.nlm.nih.gov/pubmed/35030335?tool=bestpractice.com
Chemotherapy regimens should be chosen in the context of the patient's performance status (PS), medical comorbidities, toxicity profile, and tumour biomarker expression.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 First-line treatment differs based on tumour HER2 expression.
Two-drug cytotoxic regimens are preferred for patients with advanced disease because of lower toxicity; three-drug regimens are reserved for medically fit patients with good PS and access to frequent toxicity evaluation.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
Treatment with immune checkpoint inhibitors, combined with fluoropyrimidine- and platinum-based chemotherapy, is specifically preferred for HER2-negative tumours expressing PD-L1 having a combined positive score of 1+.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 First-line options include: a fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin plus nivolumab; a fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin or cisplatin plus pembrolizumab; or a fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin or cisplatin plus tislelizumab.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
The American Society of Clinical Oncology recommends nivolumab for tumours expressing PD-L1 having a combined positive score of 5+, and pembrolizumab for tumours expressing PD-L1 having a combined positive score of 10+, in combination with platinum- and fluoropyrimidine-based chemotherapy in patients with HER2-negative oesophageal or gastro-oesophageal junction adenocarcinoma.[64]Shah MA, Kennedy EB, Alarcon-Rozas AE, et al. Immunotherapy and targeted therapy for advanced gastroesophageal cancer: ASCO guideline. J Clin Oncol. 2023 Mar 1;41(7):1470-91. https://ascopubs.org/doi/10.1200/JCO.22.02331 http://www.ncbi.nlm.nih.gov/pubmed/36603169?tool=bestpractice.com
Alternatively, a fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin or cisplatin (without an immune checkpoint inhibitor) is recommended.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
A fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin or cisplatin plus zolbetuximab (an anti-CLDN18.2 monoclonal antibody) is recommended for first-line treatment of CLDN18.2 positive, unresectable locally advanced or metastatic gastric cancer.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
Studies have demonstrated that fluorouracil can be replaced by capecitabine, and cisplatin by oxaliplatin, except in regimens including irinotecan.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 [65]Cunningham D, Rao S, Starling T, et al. Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer: The REAL 2 trial. Abstract LBA4017. Paper presented at: 2006 ASCO Annual Meeting. J Clin Oncol. 2006 Jun 20;24(18 Suppl):LBA4017. https://ascopubs.org/doi/abs/10.1200/jco.2006.24.18_suppl.lba4017 [66]Al-Batran S, Hartmann JT, Probst S, et al. A randomized phase III trial in patients with advanced adenocarcinoma of the stomach receiving first-line chemotherapy with fluorouracil, leucovorin and oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP). Abstract LBA4016. Paper presented at: 2006 ASCO Annual Meeting. J Clin Oncol. 2006 Jun 20;24(18 Suppl):LBA4016. https://ascopubs.org/doi/abs/10.1200/jco.2006.24.18_suppl.lba4016 Oxaliplatin is preferred over cisplatin owing to its lower toxicity.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 [65]Cunningham D, Rao S, Starling T, et al. Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer: The REAL 2 trial. Abstract LBA4017. Paper presented at: 2006 ASCO Annual Meeting. J Clin Oncol. 2006 Jun 20;24(18 Suppl):LBA4017. https://ascopubs.org/doi/abs/10.1200/jco.2006.24.18_suppl.lba4017 [67]Montagnani F, Turrisi G, Marinozzi C, et al. Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2011 Mar;14(1):50-5. http://www.ncbi.nlm.nih.gov/pubmed/21340667?tool=bestpractice.com Leucovorin is indicated with certain fluorouracil-based regimens. Depending on availability, the regimens may be used with or without leucovorin.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
First-line treatment for HER2 over-expression positive metastatic disease is trastuzumab (a humanised monoclonal antibody that acts on the HER2 receptor) added to chemotherapy.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 This combination has been shown to improve overall survival in patients with advanced gastric cancer.[59]Bang YJ, Van CE, Feyereislova A, et al; 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. http://www.ncbi.nlm.nih.gov/pubmed/20728210?tool=bestpractice.com A fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin or cisplatin plus trastuzumab plus pembrolizumab is the recommended first-line therapy for tumours expressing PD-L1 having a combined positive score of 1+.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Oxaliplatin is preferred over cisplatin owing to its lower toxicity.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
Folinic acid is indicated with certain fluorouracil-based regimens. Depending on availability, the regimens may be used with or without folinic acid.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
Pembrolizumab and dostarlimab are anti-PD-1 monoclonal antibodies that may be considered for patients with high microsatellite instability/mismatch repair deficiency (MSI-H/dMMR) tumours.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Other options for MSI-H/dMMR tumours include nivolumab plus ipilimumab, or a fluoropyrimidine (fluorouracil or capecitabine) plus oxaliplatin plus nivolumab or pembrolizumab.
Alternative first-line regimens for patients with HER2 overexpression negative adenocarcinoma, HER2 overexpression positive adenocarcinoma, or MSI-H/dMMR tumours include: fluorouracil plus irinotecan; docetaxel with or without cisplatin; paclitaxel with or without carboplatin or cisplatin; fluoropyrimidine (fluorouracil or capecitabine) monotherapy; or docetaxel plus cisplatin or oxaliplatin plus fluorouracil.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
In patients with peritoneal carcinoma as the only disease, intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy may be considered.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
The tropomyosin receptor kinase (TRK) inhibitors entrectinib, larotrectinib, or repotrectinib may be considered for patients with neurotrophic tropomyosin-related kinase (NTRK) gene fusion positive tumours.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocols for dosing guidelines.
Primary options
HER2-negative disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
-- AND --
nivolumab
OR
HER2-negative disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
or
cisplatin
-- AND --
pembrolizumab
OR
HER2-negative disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
or
cisplatin
-- AND --
tislelizumab
OR
HER2-negative disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
or
cisplatin
OR
CLDN18.2 positive disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
or
cisplatin
-- AND --
zolbetuximab
OR
HER2-positive disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
or
cisplatin
-- AND --
trastuzumab
OR
HER2-positive disease
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
or
cisplatin
-- AND --
trastuzumab
-- AND --
pembrolizumab
OR
MSI-H/dMMR tumours
pembrolizumab
OR
MSI-H/dMMR tumours
dostarlimab
OR
MSI-H/dMMR tumours
nivolumab
and
ipilimumab
OR
MSI-H/dMMR tumours
fluorouracil
or
capecitabine
-- AND --
oxaliplatin
-- AND --
nivolumab
or
pembrolizumab
OR
NTRK gene fusion positive tumours
entrectinib
OR
NTRK gene fusion positive tumours
larotrectinib
OR
NTRK gene fusion positive tumours
repotrectinib
Secondary options
fluorouracil
and
irinotecan
OR
docetaxel
OR
docetaxel
and
cisplatin
OR
paclitaxel
OR
paclitaxel
-- AND --
carboplatin
or
cisplatin
OR
fluorouracil
OR
capecitabine
OR
fluorouracil
-- AND --
docetaxel
-- AND --
oxaliplatin
or
cisplatin
best supportive care
Treatment recommended for ALL patients in selected patient group
The aim of best supportive care is to relieve the patients' symptoms, regardless of the stage of disease, to support the best quality of life for them and their families. For gastric cancer, interventions to relieve major symptoms may prolong life.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Endoscopic treatment, interventional radiology, gastrectomy, and chemotherapy may relieve symptoms such as pain, bleeding, nausea and vomiting, and obstruction.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
alternative chemotherapy and/or immunotherapy
Second-line and subsequent therapies depend on prior therapy and the patient's performance status. Choice of therapy generally does not depend on tumour HER2 over-expression status (except for trastuzumab deruxtecan, an antibody-drug conjugate composed of trastuzumab covalently linked to a topoisomerase I inhibitor).
Ramucirumab (a vascular endothelial growth factor inhibitor) plus paclitaxel is considered a second-line therapy for patients with locally advanced, recurrent, or metastatic disease.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 In one trial of patients with metastatic gastric adenocarcinoma (RAINBOW trial), ramucirumab added to paclitaxel (as a second-line therapy) demonstrated a significant improvement in both progression-free survival and overall survival over paclitaxel alone.[68]Wilke H, Muro K, Van Cutsem E, et al; 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. http://www.ncbi.nlm.nih.gov/pubmed/25240821?tool=bestpractice.com
Ramucirumab monotherapy has been shown to improve median overall survival in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who have disease progression after first-line platinum- or fluoropyrimidine-containing chemotherapy.[69]Fuchs CS, Tomasek J, Yong CJ, et al; 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. http://www.ncbi.nlm.nih.gov/pubmed/24094768?tool=bestpractice.com
Trastuzumab deruxtecan is recommended as second- or third-line treatment for patients with HER2 over-expression positive adenocarcinoma who had received prior trastuzumab-based therapy.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Compared with standard therapies, trastuzumab deruxtecan significantly improved response rate and overall survival in one open-label, randomised phase 2 trial of patients with treatment-refractory HER2-positive gastric or gastro-oesophageal junction adenocarcinoma.[70]Shitara K, Bang YJ, Iwasa S, et al; DESTINY-Gastric01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020 Jun 18;382(25):2419-30. https://www.nejm.org/doi/10.1056/NEJMoa2004413 http://www.ncbi.nlm.nih.gov/pubmed/32469182?tool=bestpractice.com Myelosuppression and interstitial lung disease were reported in patients receiving the drug.
Other recommended second-line therapies include: monotherapy with docetaxel, paclitaxel, or irinotecan; fluorouracil plus irinotecan; irinotecan plus cisplatin; fluorouracil plus irinotecan plus ramucirumab; irinotecan plus ramucirumab; or docetaxel plus irinotecan.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 A taxane or irinotecan, as a single agent or in combination, provides a modest improvement in overall survival compared with best supportive care.[71]Thuss-Patience PC, Kretzschmar A, Bichev D, et al. 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. http://www.ncbi.nlm.nih.gov/pubmed/21742485?tool=bestpractice.com [72]Kang JH, Lee SI, Lim do H, et al. 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. http://www.ncbi.nlm.nih.gov/pubmed/22412140?tool=bestpractice.com
Folinic acid is indicated with certain fluorouracil-based regimens. Depending on availability, the regimens may be used with or without folinic acid.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocols for dosing guidelines.
Primary options
ramucirumab
and
paclitaxel
OR
ramucirumab
OR
docetaxel
OR
paclitaxel
OR
irinotecan
OR
fluorouracil
and
irinotecan
OR
HER2-positive disease
trastuzumab deruxtecan
OR
irinotecan
and
cisplatin
OR
fluorouracil
and
irinotecan
and
ramucirumab
OR
irinotecan
and
ramucirumab
OR
docetaxel
and
irinotecan
best supportive care
Treatment recommended for ALL patients in selected patient group
The aim of best supportive care is to relieve the patients' symptoms, regardless of the stage of disease, to support the best quality of life for them and their families. For gastric cancer, interventions to relieve major symptoms may prolong life.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1 Endoscopic treatment, interventional radiology, gastrectomy, and chemotherapy may relieve symptoms such as pain, bleeding, nausea and vomiting, and obstruction.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer [internet publication]. https://www.nccn.org/guidelines/category_1
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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