Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis
Abstract
Aim: We performed a systematic review and meta-analysis to investigate the efficacy and safety of third-line (TLT) and salvage treatment (ST) in advanced or metastatic gastric cancer. Materials & methods: Eligible studies included randomized clinical trials assessing TLT and ST versus placebo or best supportive care. Outcomes of interest included: overall survival, objective response rate and disease control rate in TLT; progression-free survival in ST; grade 3–4 adverse events in ST. Results: The use of TLT and ST was superior to placebo or best supportive care in terms of prolonging overall survival and progression-free survival. Hematological toxicities were more frequent in ST. Conclusion: TLT and ST are considerable and tolerable treatment options for patients with advanced or metastatic gastric cancer. Given the substantial heterogeneities affecting the efficacy analyses, these results have to be interpreted cautiously.
Papers of special note have been highlighted as: •• of considerable interest
References
- 1. . Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer? ESMO Open 2(3), e000206 (2017).
- 2. . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68(6), 394–424 (2018).
- 3. . NCCN Gastric cancer 2017 V1. Lancet 388(10060), 2654–2664 (2016).
- 4. Chemotherapy for advanced gastric cancer – art. no. CD004064.pub2. Cochrane Database Syst. Rev. (2), CD004064 (2005).
- 5. . Advances in the treatment of gastric cancer. Curr. Opin. Gastroenterol. 34(6), 465–468 (2018).
- 6. 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 V25 study group. J. Clin. Oncol. 24(31), 4991–4997 (2006).
- 7. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: the Phase III KEYNOTE-062 study. J. Clin. Oncol. 37(Suppl. 18), LBA4007–LBA4007 (2019). •• New option as first-line treatment.
- 8. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a Phase III, open-label, randomised controlled trial. Lancet 376(9742), 687–697 •• Practice-changing study.
- 9. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, Phase III trial. Lancet 383(9911), 31–39 (2014). •• Practice-changing study in second-line treatment.
- 10. 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 III trial. Lancet Oncol. 15(11), 1224–1235 (2014). •• Practice-changing study in second-line treatment.
- 11. 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 47(15), 2306–2314 (2011).
- 12. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, Phase III randomised controlled trial. Lancet Oncol. 15(1), 78–86 (2014).
- 13. Outcomes of advanced gastric cancer patients treated with at least three lines of systemic chemotherapy. Oncologist 22(12), 1463–1469 (2017).
- 14. Outcomes of multiple salvage chemotherapy for advanced gastric cancer: implications for clinical practice and trial design. Cancer Chemother. Pharmacol. 66(4), 797–805 (2010).
- 15. Salvage chemotherapy with irinotecan and cisplatin in patients with metastatic gastric cancer failing both 5-fluorouracil and taxanes. Anticancer Drugs 16(6), 621–625 (2005).
- 16. Weekly paclitaxel for heavily treated advanced or recurrent gastric cancer refractory to fluorouracil, irinotecan, and cisplatin. Gastric Cancer 12(4), 206–211 (2009).
- 17. Efficacy and toxicity of salvage weekly paclitaxel chemotherapy in non-Asian patients with advanced oesophagogastric adenocarcinoma. Ther. Adv. Med. Oncol. 8(2), 104–112 (2016).
- 18. . Prognostic factor analysis of third-line chemotherapy in patients with advanced gastric cancer. Gastric Cancer 14(3), 249–256 (2011).
- 19. 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. 30(13), 1513–1518 (2012).
- 20. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-Arm, Phase II trial. J. Clin. Oncol. 31(26), 3219–3225 (2013).
- 21. Randomized, double-blind, placebo-controlled Phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J. Clin. Oncol. 34(13), 1448–1454 (2016).
- 22. . Trifluridine / tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo- controlled, Phase III trial. Lancet Oncol. 19(11), 1437–1448 (2018).
- 23. 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 III trial. Lancet 390(10111), 2461–2471 (2017).
- 24. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, Phase III GRANITE-1 study. J. Clin. Oncol. 31(31), 3935–3943 (2013).
- 25. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): a multinational placebo-controlled phase II Trial. J. Clin. Oncol. 34(23), 2728–2735 (2016).
- 26. . Second-line chemotherapy for patients with advanced gastric cancer. Gastric Cancer 20(3), 395–406 (2017).
- 27. Prognostic factors in 868 advanced gastric cancer patients treated with second-line chemotherapy in the real world. Gastric Cancer 20(5), 825–833 (2017).
- 28. Estimating survival probabilities of advanced gastric cancer patients in the second-line setting: the gastric life nomogram. Oncology 95(6), 344–352 (2018).
- 29. Anti-angiogenic therapy in patients with advanced gastric and gastroesophageal junction cancer: a systematic review. Cancer Res. Treat. 49(4), 851–868 (2017).
- 30. . Advanced gastric adenocarcinoma: optimizing therapy options. Expert Rev. Clin. Pharmacol. 10(3), 263–271 (2017).
- 31. Quality of life in the trastuzumab for gastric cancer trial. Oncologist 19(7), 712–719 (2014).
- 32. Quality of life with biweekly docetaxel and capecitabine in advanced gastro-oesophageal cancer. Support Care Cancer 25(9), 2771–2777 (2017).
- 33. . Third-line chemotherapy in advanced gastric cancer: a systematic review and meta-analysis. Medicine (Baltimore) 96(24), e6884 (2017).
- 34. . Third-line systemic treatment versus best supportive care for advanced/metastatic gastric cancer: a systematic review and meta-analysis. Crit. Rev. Oncol. Hematol. 116, 68–81 (2017).
- 35. . Molecular classification of gastric cancer. Ann. Oncol. 27(5), 763–769 (2016).
- 36. . Updates on management of gastric cancer. Curr. Oncol. Rep. 21(8), 67 (2019).
- 37. . Immunotherapy for gastric cancer: a focus on immune checkpoints. Target. Oncol. 11(4), 469–477 (2016).
- 38. . Immunotherapy for gastric cancer: time for a personalized approach? Int. J. Mol. Sci. 19(6), 1602 (2018).
- 39. Immunotherapy for gastric cancers: emerging role and future perspectives. Expert Rev. Clin. Pharmacol. 10(6), 609–619 (2017).