Gastric Cancer: Pharmacologic Management

Gastric cancer is the fifth most common malignant cancer and the fourth leading cause of cancer-related mortality globally.¹ Gastric cancers — malignancies that arise from the stomach — are categorized into 4 types: adenocarcinoma, gastrointestinal stromal tumors (GISTs), carcinoid tumors, and gastric lymphoma.² The prognosis of localized gastric cancer is favorable, with a 5-year survival rate of 74.7%.³ However, only 28.8% of gastric cancers are diagnosed in the early stages, and the 5-year survival rate decreases significantly with disease progression: 35% for stage II and 25% or less for stage III.⁴ 

Risk factors for gastric cancer include^2,4:

• Advanced age; 
• Male sex;
• Helicobacter pylori infection;
• Black or Asian race;
• High salt intake;
• Diet low in fruits and vegetables; 
• Chronic atrophic gastritis;
• Intestinal metaplasia;
• Gastric adenomatous polyps;
• Family history of gastric cancer;
• Smoking; and
• Epstein-Barr virus infection.

Early-stage gastric cancer is often asymptomatic, and in many cases, symptoms only manifest in advanced stages. Symptoms of gastric cancer include:

• Unintentional weight loss; 
• Abdominal pain and swelling;
• Nausea and vomiting;
• Indigestion or heartburn;
• Feeling full after eating only a little bit of food;
• Anorexia;
• Black, tarry stools caused by gastric bleeding; and
• Anemia.

Treatment decisions for gastric cancer are made based on the location and the extent of metastases, as well as the patient’s general health and toxicity of the potential treatment. Treatment of gastric cancer consists of surgical resection, preoperative and/or postoperative chemotherapy with or without radiation therapy, and targeted therapy. 

Gastric Cancer Types

Gastric cancers are categorized into 4 types according to the location of origin: adenocarcinoma, GISTs, carcinoid tumors, and lymphoma. Approximately 90% to 95% of all gastric cancers are adenocarcinomas. Gastrointestinal stromal tumors make up less than 1% of all gastrointestinal tumors. Gastric carcinoid tumors and gastric lymphomas are rare, but their incidence has been increasing in recent years.²

Gastric Adenocarcinomas

Gastric adenocarcinomas originate in mucosal cells and are the most common type of gastric cancer. They are divided into 2 histologic types — intestinal and diffuse — according to their microscopic configuration and growth pattern. Intestinal-type gastric adenocarcinomas are morphologically similar to adenocarcinomas of the intestinal tract and grow in glandular — rather than infiltrative — patterns. They are believed to arise from chronic gastritis, often from H pylori infection and autoimmune gastritis. Diffuse-type gastric adenocarcinomas are characterized by diffuse and deep infiltration of the stomach wall by noncohesive tumor cells. Diffuse-type cancers have a high incidence, are found more often in young patients, and have a worse prognosis.⁵  

Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors are uncommon mesenchymal subepithelial tumors that arise from interstitial cells of Cajal, which transmit signals between smooth muscle cells and the autonomic nervous system. Although rare, GISTs are characterized by high rates of recurrence and metastasis.⁶ 

Gastric Carcinoid Tumors 

Gastric carcinoid tumors are neuroendocrine tumors that are often asymptomatic until the late stages. They are frequently found as an incidental finding during upper gastrointestinal endoscopies and are associated with hypergastrinemia.⁷ 

Gastric Lymphomas

Gastric lymphomas account for only 3% of all gastric cancers. The majority are caused by H pylori infection, which leads to chronic gastritis and the development of mucosa-associated lymphoid tissue (MALT) lymphoma, a rare type of non-Hodgkin lymphoma. Eradication of H pylori alone results in remission in 60% to 80% of gastric lymphoma cases. The authors of a recent literature review report an increased risk for gastric adenocarcinoma after gastric MALT lymphoma.⁸

Treatment of Gastric Cancer

Treatment decisions for gastric cancer are made based on the cancer stage, the patient’s general health, and the toxicity of the potential treatment. Treatment of gastric cancer consists of: 

• Surgical resection;
• Neoadjuvant and/or adjuvant chemotherapy;
• Radiation therapy; or
• Targeted therapy.

Stage 0

Treatment options for early local (stage 0) gastric cancer with no lymph node involvement are gastrectomy with lymphadenectomy and endoscopic mucosal resection (EMR). Studies have shown that more than 90% of patients who undergo gastrectomy with lymphadenectomy for gastric cancer survive beyond 5 years.² 

Stage I

Treatment options for patients with localized, resectable disease (stage I) include surgical resection with lymphadenectomy or EMR with adjuvant chemoradiation or neoadjuvant chemotherapy, depending on the presence of node involvement and muscle invasion.² 

Stage II and Stage III

For stage II and III gastric cancers, treatment options include surgical resection with lymphadenectomy, neoadjuvant chemotherapy, adjuvant chemoradiation therapy, and adjuvant chemotherapy. Considering the high risk of recurrence of gastric cancer at these stages, neoadjuvant and adjuvant therapies are recommended in addition to surgery. Neoadjuvant chemotherapy is recommended for patients at high risk of developing distant metastases. Adjuvant chemotherapy with or without radiation therapy is recommended for patients who have undergone surgical resection without neoadjuvant therapy and are at high risk for recurrence.²

Stage IV

Systemic therapy regimens used for the treatment of stage IV, unresectable, advanced, recurrent, or metastatic gastric cancer consist of combinations of cytotoxic, targeted, and immunotherapies, as outlined below.    

1. First-line therapy options for human epithelial growth factor receptor-2 (HER2)-negative tumors include²:

• Chemotherapy with fluorouracil (5-FU) or capecitabine alone or with oxaliplatin and nivolumab;
• Triplet: 5-FU in combination with epirubicin and cisplatin, etoposide and leucovorin, doxorubicin and methotrexate, leucovorin and irinotecan, or docetaxel and cisplatin/oxaliplatin;
• Doublet: A taxane and cisplatin/carboplatin, 5-FU and cisplatin, or capecitabine and oxaliplatin; and
• Single agents: 5-FU or capecitabine, or a taxane.

2. First-line systemic therapy for HER2-positive tumors consists of nivolumab or trastuzumab with chemotherapy.²

3. Second-line systemic therapy treatment options include²: 

• Ramucirumab alone or with paclitaxel; and
• Trastuzumab deruxtecan for HER2-positive tumors.

4. Third-line systemic therapy consists of oral cytotoxic therapy with trifluridine/tipiracil.²

Pharmacologic Treatment of Gastric Cancer 

With the exception of early-stage, localized tumors, adjuvant and neoadjuvant systemic therapies — with or without radiotherapy — have been shown to improve outcomes, especially in patients with locally advanced disease. Combination chemotherapy regimens with targeted therapy or immunotherapy agents have shown effectiveness in advanced and metastatic disease.⁹  

Chemotherapy

The standard-of-care chemotherapy treatment of gastric cancer consists of fluoropyrimidine/platinum backbone with or without a third chemotherapy, targeted therapy, or immunotherapy agent. Variations of fluoropyrimidine/platinum regimens using alternative agents can be considered according to cancer stage and the patient’s tolerability to toxicity.   

Capecitabine. Capecitabine is a fluoropyrimidine that is converted to 5-FU in cancer cells. It is indicated for the treatment of unresectable or metastatic gastric, esophageal, or gastroesophageal junction (GEJ) cancer in combination with a chemotherapy regimen. It is also used to treat patients with HER2-overexpressing metastatic gastric or GEJ adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen.¹⁰ 

Capecitabine is administered as follows:

• 625 mg/m² orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles, together with platinum-containing chemotherapy; or 
• 850 mg/m² or 1000 mg/m² orally twice daily for the first 14 days of each 21-day cycle in combination with oxaliplatin 130 mg/m² given intravenously (IV) on day 1 of each cycle. 
• For HER2-overexpressing metastatic gastric or GEJ adenocarcinoma, 1000 mg/m² orally twice daily for the first 14 days of each 21-day cycle in combination with cisplatin and trastuzumab.

Serious adverse reactions among patients with dihydropyrimidine dehydrogenase (DPD) deficiency has been reported with the use of capecitabine. Due to increased risk for acute toxicity, capecitabine is not recommended for use in patients with homozygous or compound heterozygous DPYD variants. Other adverse reactions to capecitabine include:

• Cardiotoxicity;
• Diarrhea;
• Dehydration;
• Renal toxicity;
• Serious skin toxicities;
• Myelosuppression;
• Hyperbilirubinemia; and
• Embryo-fetal toxicity.

The most common side effects associated with capecitabine are hand-foot syndrome, diarrhea, and nausea.

Capecitabine may interact with the following medications and they should not be taken concomitantly:

• Allopurinol
• Leucovorin: 
• CYP2C9 substrates: 
• Vitamin K antagonists, such as warfarin:
• Phenytoin
• Nephrotoxic drugs

The pregnancy status of female patients should be verified before treatment, and pregnant patients should be advised of the potential risk to the fetus. Birth control should be used by female patients with reproductive potential and male patients who have female partners with reproductive potential during treatment and for 6 months and 3 months, respectively, following treatment. Capecitabine may impair fertility in female and male patients. Breastfeeding should be discontinued during treatment with capecitabine. Safe and effective use of capecitabine in pediatric patients has not been established. Treatment with capecitabine has caused increased gastrointestinal toxicity in older patients compared with younger patients. 

Docetaxel. Docetaxel is a cytotoxic agent that disrupts cell division in cancer cells by inhibiting microtubule formation. It is indicated for treatment of untreated, advanced gastric adenocarcinoma in combination with cisplatin and 5-FU.¹¹ 

Docetaxel is administered as follows:

• 75 mg/m² IV over 1 hour, followed by IV infusion of cisplatin at 75 mg/m² over 1 to 3 hours (both on day 1 only), followed by fluorouracil 750 mg/m²/d IV over 24 hours for 5 days, starting at the end of the cisplatin administration, with the treatment being repeated every 3 weeks;
• Premedicate with antiemetics for cisplatin administration; or
• Premedicate with oral corticosteroids prior to docetaxel administration.

Serious adverse reactions reported with docetaxel use include:

• Toxic deaths;
• Hepatic impairment;
• Hematologic effects;
• Enterocolitis and neutropenic colitis;
• Hypersensitivity reactions;
• Severe fluid retention;
• Second primary malignancies;
• Cutaneous reactions;
• Neurologic reactions;
• Eye disorders;
• Asthenia; and
• Embryo-fetal toxicity.

The most common side effects reported with docetaxel include:

• Infections;
• Low neutrophil count;
• Anemia;
• Low platelet levels;
• Neuropathy;
• Shortness of breath;
• Constipation;
• Fluid retention;
• Nausea;
• Diarrhea;
• Vomiting;
• Mucositis;
• Alopecia;
• Skin reactions; and
• Myalgia.

Docetaxel is not recommended for use in patients with hypersensitivity to either docetaxel or polysorbate 80, or in patients with a neutrophil count less than 1500 cells/mm³. Cytochrome P450 3A4 inducers, inhibitors, or substrates can affect docetaxel metabolism and should not be taken together with docetaxel. 

The pregnancy status of female patients should be checked before starting treatment. Pregnant patients should be warned of the risk of fetal harm, and contraception should be used during treatment and for 6 months following treatment for female patients of reproductive potential. Male patients and female partners with reproductive potential should use contraception during treatment and for 3 months following treatment. Docetaxel may impair fertility in male patients of reproductive potential. Breastfeeding should be discontinued during treatment and for 1 week after treatment completion. The efficacy of docetaxel has not been established in pediatric patients. The dose may need to be reduced for older patients due to greater frequency of decreased lung, kidney, or cardiac function; comorbidities; and use of other medications. 

Doxorubicin. Doxorubicin is an anthracycline topoisomerase II inhibitor used in the treatment of metastatic gastric carcinoma.¹² It is administered at 60 to 75 mg/m² IV every 21 days as a single agent. In combination therapies, it is administered at 40 to 75 mg/m² IV every 21 to 28 days.  

Serious adverse reactions reported with doxorubicin use include:

• Cardiomyopathy and arrhythmias;
• Secondary malignancies;
• Extravasation and tissue necrosis;
• Severe bone marrow suppression;
• Severe lung impairment;
• Tumor lysis syndrome;
• Hypersensitivity;
• Increased radiation-induced toxicity; and
• Embryo-fetal toxicity.

The most common side effects associated with doxorubicin include alopecia, nausea, and vomiting. 

Use of doxorubicin with inhibitors and inducers of CYP3A4, CYP2D6, and/or P-glycoprotein such as verapamil, phenobarbital, phenytoin, and St. John’s wort should be avoided. Concurrent use of doxorubicin and trastuzumab should be avoided due to the increased risk of cardiac dysfunction. Paclitaxel, dexrazoxane, and 6-mercaptopurine should not be used together with doxorubicin.  

The pregnancy status of female patients should be verified prior to treatment, and pregnant patients should be advised of the potential hazard to the fetus. Female patients with reproductive potential and male patients who have female partners with reproductive potential should use contraception during and for 6 months after treatment. Doxorubicin may impair fertility in female and male patients. Breastfeeding should be discontinued during treatment. Pediatric patients using doxorubicin are at risk of developing late cardiovascular dysfunction, prepubertal growth failure, and temporary gonadal impairment. 

Fluorouracil. Fluorouracil (5-FU) is a nucleoside metabolic inhibitor indicated for treatment of gastric adenocarcinoma. It is administered at 200 mg/m² to 1000 mg/m² IV infusion over 24 hours as part of a platinum-containing combination chemotherapy regimen. Frequency of dosing and cycle length depend on the dose of fluorouracil and which regimen is being administered.¹³ 

Serious adverse reactions reported with the use of 5-FU include:

• Cardiotoxicity;
• Hyperammonemic encephalopathy;
• Neurologic toxicity;
• Diarrhea;
• Hand-foot syndrome;
• Bone marrow suppression;
• Mucositis; and
• Embryo-fetal toxicity.

Fluorouracil should not be used in patients with near complete or complete absence of DPD activity. Concomitant use of 5-FU with warfarin should be avoided due to the risk of elevated coagulation times.

The pregnancy status of female patients should be verified prior to treatment with 5-FU. Pregnant patients should be advised of the potential hazard to the fetus, and birth control should be used by female patients with reproductive potential and male patients who have female partners with reproductive potential during treatment and for 3 months following treatment. Fluorouracil may cause fertility impairment in female and male patients during treatment. The safe and effective use of 5-FU has not been established in pediatric patients. 

Mitomycin. Mitomycin is an antibiotic shown to have antitumor activity. It is indicated for the treatment of metastatic gastric adenocarcinoma in combination with other chemotherapy agents. It can also be used for palliative treatment if the tumor fails to respond to other therapies.¹⁴ Mitomycin is administered at 20 mg/m² IV every 6 to 8 weeks. 

Serious adverse reactions reported with mitomycin use include:

• Bone marrow suppression; and
• Hemolytic uremic syndrome.

The most common side effects associated with mitomycin are:

• Headache;
• Blurring of vision;
• Confusion;
• Fatigue;
• Drowsiness; and
• Inflammation of veins.

The safety of mitomycin use during pregnancy and the safety and effectiveness of mitomycin in pediatric patients have not been established. 

Trifluridine and tipiracil. Trifluridine and tipiracil is an oral cytotoxic agent that inhibits proliferation of cancer cells. It is used in the treatment of metastatic gastric or GEJ cancer previously treated with 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum agent, either a taxane or irinotecan, and HER2/neu-targeted therapy.¹⁵ The recommended dosage of trifluridine and tipiracil is 35 mg/m² taken orally twice a day with food on day 1 through day 5 and day 8 through day 12 of each 28-day cycle. 

Serious adverse reactions reported with trifluridine and tipiracil use include:

• Severe bone marrow suppression; and
• Embryo-fetal toxicity.

The most common side effects associated with trifluridine and tipiracil are:

• Anemia;
• Low neutrophil count;
• Fatigue;
• Nausea;
• Low platelet levels;
• Decreased appetite;
• Diarrhea; and
• Vomiting.

The pregnancy status of female patients should be checked before starting treatment, and pregnant patients should be advised of the risk of harm to the fetus. Female patients of reproductive potential and male patients with female partners of reproductive potential should use effective contraception during treatment and for 6 months and 3 months, respectively, after treatment. Breastfeeding should be discontinued during treatment and for 1 day following the last dose. The use of trifluridine and tipiracil has not been evaluated in pediatric patients. Trifluridine and tipiracil was associated with a higher incidence of low neutrophil and platelet counts and anemia in patients 65 years of age and older.

Targeted Therapy

Targeted therapy agents directed against biomarkers found in tumor cells and/or involved in tumorigenesis have increased the treatment options for gastric cancer. Antibodies directed against HER2 and vascular endothelial growth factor receptor 2 (VEGFR-2) have been demonstrated to improve survival and are used for treatment of advanced gastric cancer. 

Trastuzumab. Trastuzumab is an anti-HER2 monoclonal antibody used in combination with cisplatin and capecitabine or 5-FU for treatment of patients with HER2-positive metastatic gastric cancer or GEJ cancer with no prior treatment. It should be noted that trastuzumab cannot be substituted for/with ado-trastuzumab emtansine. HER2 expression status of the tumor should be assessed to select patients likely to have treatment benefit. Trastuzumab may be combined with pembrolizumab and chemotherapy (5-FU and cisplatin or oxaliplatin with capecitabine) as treatment for HER2-positive metastatic gastric adenocarcinoma.¹⁶ Trastuzumab is administered at an initial dose of 8 mg/kg IV infusion over 90 minutes, followed by 6 mg/kg over 30 to 90 minutes every 3 weeks. 

Serious adverse reactions reported with trastuzumab use include:

• Cardiomyopathy;
• Infusion reactions;
• Pulmonary toxicity;
• Embryo-fetal toxicity; and
• Exacerbation of chemotherapy-induced neutropenia.

The most common side effects associated with trastuzumab include:

• Low neutrophil count;
• Diarrhea;
• Fatigue;
• Anemia;
• Stomatitis;
• Upper respiratory tract infection;
• Thrombocytopenia;
• Mucosal inflammation; and
• Nasopharyngitis.

Due to the long washout period of trastuzumab, anthracyclines should be avoided for up to 7 months after completion of trastuzumab treatment. 

Trastuzumab use has been associated with cases of oligohydramnios, resulting in pulmonary hypoplasia, skeletal abnormalities, and neonatal death. The pregnancy status of female patients should be verified before treatment. Pregnant patients should be advised of the risk of harm to the fetus and monitored for oligohydramnios if trastuzumab is used during pregnancy or within 7 months before conception. Birth control should be used by female  patients of reproductive potential to avoid pregnancy during treatment and for 7 months following the completion of treatment. The safe and effective use of trastuzumab has not been established in pediatric patients. The risk of cardiac dysfunction was increased with trastuzumab in patients older than 65 years.

Fam-trastuzumab deruxtecan-nxki. Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate composed of an anti-HER2 antibody with a topoisomerase I inhibitor connected by a cleavable tetrapeptide-based linker. It binds to HER2 on tumor cells and becomes internalized and leads to DNA damage and cell death in the tumor cells. Fam-trastuzumab deruxtecan-nxki  is indicated for the treatment of patients with locally advanced or metastatic HER2-positive gastric cancer or GEJ adenocarcinoma who have received a prior trastuzumab-based regimen.¹⁷ In an international, open-label, randomized, phase II trial (DESTINY-Gastric01; ClinicalTrials.gov Identifier: NCT03329690) that included 187 patients from Japan and South Korea with HER2-positive advanced gastric cancer that had progressed after at least 2 previous therapies (including trastuzumab), fam-trastuzumab deruxtecan-nxki was shown to have a significantly higher objective response rate and better overall survival compared with chemotherapy.¹⁸ Fam-trastuzumab deruxtecan-nxki is given at 6.4 mg/kg IV infusion once every 3 weeks.

Serious adverse reactions reported with use of fam-trastuzumab deruxtecan-nxki include:

• Low neutrophil count;
• Interstitial lung disease; and
• Left ventricular dysfunction.

The most common side effects associated with fam-trastuzumab deruxtecan-nxki are:

• Decreased hemoglobin;
• Decreased white blood cell count;
• Decreased neutrophil count;
• Decreased lymphocyte count;
• Decreased platelet count;
• Nausea;
• Fatigue;
• Diarrhea;
• Vomiting;
• Constipation;
• Fever; and
• Alopecia.

The pregnancy status of female patients should be checked prior to treatment, and pregnant patients should be advised of potential risk of harm to the fetus. Effective contraception should be used by female patients of reproductive potential during treatment and for 7 months following the last dose. Male patients with female partners of reproductive potential should use contraception during and for 4 months after treatment. Fam-trastuzumab deruxtecan-nxki may impair fertility in male patients. Breastfeeding should be discontinued during treatment and for 7 months after treatment. The safety and effectiveness of fam-trastuzumab deruxtecan-nxki have not been established in pediatric patients. 

Ramucirumab. Ramucirumab is a fully humanized monoclonal antibody directed against VEGFR-2. It is indicated for treatment of advanced gastric cancer or GEJ adenocarcinoma, as a single agent or in combination with paclitaxel, following prior chemotherapy with fluoropyrimidine or a platinum agent.¹⁹ In an international, phase 3, placebo-controlled trial (REGARD; ClinicalTrials.gov Identifier: NCT00917384), ramucirumab was shown to improve overall survival in patients with cisplatin-refractory or 5-FU-refractory, stage IV gastric cancer compared with those receiving placebo.²⁰ In the international, double-blinded, phase 3 RAINBOW trial (ClinicalTrials.gov Identifier: NCT01170663), ramucirumab given in combination with paclitaxel was shown to improve overall survival.²¹

Ramucirumab is administered as follows:

• 8 mg/kg IV infusion over 60 minutes every 2 weeks, as a single agent or in combination with weekly paclitaxel;
• Administered prior to paclitaxel in combination therapy;
• Premedicate with histamine H1 antagonist; and
• Premedicate with dexamethasone and acetaminophen prior to ramucirumab infusion for patients with a prior infusion reaction. 

Serious adverse reactions reported with ramucirumab use include: 

• Arterial thromboembolic events;
• Hypertension;
• Infusion-related reactions;
• Gastrointestinal perforation;
• Clinical deterioration in patients with cirrhosis; and
• Reversible posterior leukoencephalopathy syndrome.

The most common side effects associated with ramucirumab include:

• Hypertension;
• Diarrhea;
• Fatigue; and
• Low neutrophil count.

The pregnancy status of female patients should be verified before treatment. Pregnant patients should be advised of the risk of harm to the fetus and the potential risk of breastfeeding while on ramucirumab. Female patients with reproductive potential should use effective contraception. Ramucirumab may impair fertility in female patients. The safe and effective use of ramucirumab has not been established in pediatric patients.  

Immunotherapy

Current immunotherapy options for gastric cancer consist of programmed death-1 (PD-1) inhibitors, which are immune checkpoint inhibitors that target checkpoint proteins to circumvent the cancer cells’ immune escape and initiate an immune response against them, leading to their cell death.²²  

Nivolumab. Nivolumab is a monoclonal antibody to the PD-1 receptor that blocks the binding of programmed death ligand-1 (PD-L1) to the PD-1 receptor on the surface of cancer cells.²³ In 2016, nivolumab was approved by the FDA for the treatment of advanced or metastatic gastric cancer, GEJ cancer, and esophageal adenocarcinoma in combination with fluoropyrimidine-containing and platinum-containing chemotherapy, based on the results of the CheckMate-649 study (ClinicalTrials.gov Identifier: NCT02872116) showing improved survival with nivolumab.²⁴ 

Nivolumab is administered as follows:

• 360 mg every 3 weeks with fluoropyrimidine-containing and platinum-containing chemotherapy; or
• 240 mg every 2 weeks with fluoropyrimidine-containing and platinum-containing chemotherapy.

Serious adverse reactions reported with nivolumab use include:

• Immune-related adverse reactions;
• Infusion-related reactions;
• Complications of allogeneic hematopoietic stem cell transplantation (HSCT); and
• Embryo-fetal toxicity.

The most common side effects associated with nivolumab include:

• Fatigue;
• Diarrhea;
• Nausea;
• Constipation;
• Decreased appetite;
• Rash; and
• Vomiting.

The pregnancy status of female patients should be checked before treatment. Pregnant patients should be advised of the risk of harm to the fetus, and contraception should be used during and for 5 months following treatment with nivolumab. Breastfeeding should be discontinued during treatment and for 5 months following completion of treatment. The safe and effective use of nivolumab for treatment of gastric cancer in pediatric patients has not been established.  

Pembrolizumab. Pembrolizumab is a monoclonal antibody to the PD-1 receptor. It is used for the first-line treatment of unresectable, advanced, or metastatic HER2-positive gastric cancer in combination with trastuzumab and chemotherapy regimens using fluoropyrimidine or platinum agents.²⁵ Pembrolizumab is administered at 200 mg IV every 3 weeks or 400 mg IV every 6 weeks.

Serious adverse reactions reported with pembrolizumab use include:

• Immune-related adverse reactions;
• Infusion-related reactions;
• Complications of allogeneic HSCT; and
• Embryo-fetal toxicity.

The most common side effects associated with pembrolizumab include:

• Fatigue;
• Diarrhea;
• Nausea;
• Rash;
• Hypertension; and
• Vomiting.

The pregnancy status of female patients should be checked prior to treatment. Due to the potential of transmission to the fetus, pregnant patients should be warned of the risk of fetal harm, and contraception should be used during and for 4 months after the treatment. Breastfeeding should be discontinued during treatment and for 4 months after the final dose. The safety and effectiveness of pembrolizumab have not been established in pediatric patients.  

Guidelines for Management of Gastric Cancer

The following resources are available to assist in clinical decision-making for gastric cancer:

• NCCN Clinical Practice Guidelines in Oncology – Gastric Cancer. Version 1.2023. National Comprehensive Cancer Network®. https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf

• Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline | Journal of Clinical Oncology (ascopubs.org)

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Author Bio

Bora Lee, PhD, earned a Bachelor of Science in biology from Boston College and a PhD in Molecular and Cellular Biology from the University of Massachusetts Amherst. She has more than 10 years of translational research experience in reproductive medicine and women’s health, with a focus on fertility and placental health. She is passionate about improving people’s lives by helping them to make informed health decisions.