What is the management of gastric cancer (gastric carcinoma)?

From the Guidelines

Gastric cancer management should involve a multidisciplinary team approach, with treatment strategies based on the cancer stage, patient factors, and genetic predisposition, as outlined in the NCCN Guidelines for Gastric Cancer 1. The management of gastric cancer is complex and requires a comprehensive approach. Key factors to consider include the stage of the cancer, the patient's performance status, and the presence of any genetic predisposition syndromes.

• For patients with unresectable or metastatic disease, best supportive care and palliative management are essential, with options for systemic therapy or chemoradiation depending on the patient's performance status and prior treatment 1.
• Targeted therapies, such as trastuzumab plus chemotherapy for HER2 overexpression–positive tumors, and nivolumab combined with chemotherapy for tumors with PD-L1 expression levels by CPS of $5, have shown promising results in the treatment of advanced gastric cancer 1.
• Other options for second-line or subsequent therapy include ramucirumab, pembrolizumab, and dostarlimab-gxly, depending on the patient's tumor characteristics and prior treatment 1.
• Entrectinib and larotrectinib are recommended for second-line or subsequent therapy for NTRK gene fusion-positive tumors 1.
• The NCCN Guidelines for Gastric Cancer emphasize the importance of multidisciplinary team management and encourage patients to participate in well-designed clinical trials investigating novel therapeutic strategies 1.

From the FDA Drug Label

The efficacy of CYRAMZA was evaluated in REGARD (NCT00917384), a multinational, randomized, double-blind, multicenter study in patients with locally advanced or metastatic gastric cancer (including adenocarcinoma of the GEJ) who previously received platinum- or fluoropyrimidine-containing chemotherapy The major efficacy outcome measure was overall survival (OS). An additional efficacy outcome measure was progression-free survival (PFS). Efficacy results are shown in Table 10 and Figure 1 Table 10: Efficacy Results in REGARD CYRAMZA + BSC N=238 Placebo + BSC N=117 Overall Survival Number of deaths (%) 179 (75%) 99 (85%) Median – months (95% CI) 5.2 (4.4,5.7) 3.8 (2.8,4.7) Hazard Ratio (95% CI) 0.78 (0.60,0. 998) Stratified Log-rank p-value 0.047 Progression-free Survival Number of events (%) 199 (84%) 108 (92%) Median – months (95% CI) 2.1 (1.5,2.7) 1.3 (1.3,1.4) Hazard Ratio (95% CI) 0.48 (0.38,0.62) Stratified Log-rank p-value <0. 001

The management of gastric cancer with ramucirumab (CYRAMZA) includes:

• Overall Survival (OS): Ramucirumab showed a statistically significant improvement in OS compared to placebo, with a median OS of 5.2 months (95% CI: 4.4,5.7) versus 3.8 months (95% CI: 2.8,4.7) for placebo.
• Progression-Free Survival (PFS): Ramucirumab also showed a statistically significant improvement in PFS compared to placebo, with a median PFS of 2.1 months (95% CI: 1.5,2.7) versus 1.3 months (95% CI: 1.3,1.4) for placebo.
• Treatment Regimen: Ramucirumab was administered as an intravenous infusion at a dose of 8 mg/kg every 2 weeks.
• Patient Population: The study included patients with locally advanced or metastatic gastric cancer who had previously received platinum- or fluoropyrimidine-containing chemotherapy. 2

From the Research

Gastric Cancer Management

• Gastric adenocarcinoma is a complex disease that requires a thorough multidisciplinary approach for appropriate management 3
• Management strategies vary in different regions of the world and have changed over time 3
• The best outcomes are likely related to early detection, preoperative reduction of tumor burden with immunochemotherapy, consistent surgical technique for resection, and postoperative eradication of tumor cells 3

Treatment Approaches

• Biweekly docetaxel, fluorouracil, leucovorin, oxaliplatin (TEF) as first-line treatment for advanced gastric cancer and adenocarcinoma of the gastroesophageal junction has shown safety and efficacy in a multicenter cohort 4
• Docetaxel, oxaliplatin, and 5-fluorouracil (DOF) in metastatic and unresectable gastric/gastroesophageal junction adenocarcinoma has demonstrated high activity and is a feasible three-drug combination therapy 5
• Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have improved the prognosis of gastric cancer when combined with surgery with curative intent 6, 7

Surgical Techniques

• Complete surgical resection offers the chance of cure for localized gastric cancer 6
• Radical surgical R0 resections are the basis of cure for gastric cancer, but surgery alone only provides long-term survival in 20-30% of patients with advanced-stage disease 7
• Curative intent surgery after response to TEF was performed in seven patients (17%) in a study 4

Chemotherapy and Adjuvant Treatment

• Adjuvant chemoradiation with 5-fluorouracil/leucovorin significantly improves disease-free survival and overall survival 6
• Perioperative chemotherapy has shown survival benefit in the UK Medical Research Council Adjuvant Gastric trial 6
• The combination of cisplatin with intravenous or oral fluoropyrimidines has been the integral component of neoadjuvant and adjuvant strategies 7