Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

Abstract

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

Keywords: advanced gastric cancer; ramucirumab; targeted therapy; treatment strategy.

Figure 1

Median overall survival by chemotherapy regimen in the first- and the second-line setting for advanced gastric cancer.

Figure 2

Advanced gastric cancer: a tale of two diseases. BSC, best supportive care; ECOG, Eastern Cooperative Oncology Group.

Figure 3

Algorithm for personalised allocation to treatments in patients with advanced gastric cancer. BSC, best supportive care; CF, cisplatin and 5-FU; DCF, docetaxel, cisplatin and fluorouracil; ECF, epirubicin, cisplatin and 5-FU; OS, overall survival; XP, capecitabine and cisplatin, epirubicin, oxaliplatin, and capecitabine, paclitaxel and ramucirumab.