Clinical Edge Journal Scan

Clinical Edge Journal Scan Commentary: Gastric Cancer, May 2022

Author and Disclosure Information

 

There have been eff orts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab. 4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors. 8 The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting ( NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

  1. 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;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
  2. Van Cutsem E, Moiseyenko VM , Tjulandin S , et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi: 10.1200/JCO.2006.06.8429 Source
  3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
  4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
  5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
  6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
  7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
  8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the Ge rman AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

Pages

Recommended Reading

Gastric cancer: Function-preserving surgery fails to show noninferiority
MDedge Hematology and Oncology
HER2-negative gastric cancer: Docetaxel-based chemotherapy does not improve outcomes
MDedge Hematology and Oncology
Gastric cancer: Add-on apatinib to neoadjuvant chemotherapy shows good response
MDedge Hematology and Oncology
Gastric cancer: Perioperative capecitabine plus oxaliplatin shows good survival
MDedge Hematology and Oncology
Early gastric cancer: Undifferentiated-predominant mixed-type is more aggressive
MDedge Hematology and Oncology
Gastric cancer: Modified Glasgow prognostic score predicts sarcopenia
MDedge Hematology and Oncology
Cimetropium bromide use during endoscopy improves gastric neoplasm detection rate
MDedge Hematology and Oncology
Salt intake is associated with higher risk for gastric cancer
MDedge Hematology and Oncology
Gastric cancer: LNR can help select patients for adjuvant chemotherapy
MDedge Hematology and Oncology
Gastric cancer: Robotic gastrectomy has superior outcomes in patients with obesity
MDedge Hematology and Oncology