Date Published: June 7, 2018
Publisher: Public Library of Science
Author(s): In Sil Choi, Mihong Choi, Ju Hyun Lee, Jee Hyun Kim, Koung Jin Suh, Ji Yun Lee, Beodeul Kang, Ji-Won Kim, Se-Hyun Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Soo-Mee Bang, Jong Seok Lee, Keun-Wook Lee, Ju-Seog Lee.
There is limited data on third-line chemotherapy in patients with metastatic gastric cancer (MGC). This study was conducted to assess third-line treatment patterns, outcomes, and clinical parameters related to survival outcomes in patients with MGC.
Using the Korean Health Insurance Review and Assessment Service (HIRA) database, a nationwide population-based outcomes study was conducted. From the HIRA database, patients newly diagnosed in 2010 with MGC were identified (N = 1,871), and of these, 229 patients who had received third-line chemotherapy were finally selected for this study.
Prior to third-line chemotherapy, more than 90% of patients received fluoropyrimidine and platinum, and 43.7% and 40.6% received taxane and irinotecan, respectively. Various third-line chemotherapy regimens containing taxane (docetaxel or paclitaxel), irinotecan, or oxaliplatin were prescribed. The median overall survival (OS) of all patients receiving third-line chemotherapy was 4.4 months. The median time from the start date of first-line chemotherapy to the start date of third-line chemotherapy (TF1T3) was 9.5 months, and a longer TF1T3 was the only factor that was significantly associated with an increased OS. The median OS of patients who had received fluoropyrimidine, platinum, and taxane followed by third-line irinotecan-based therapy was similar to that of patients who had received fluoropyrimidine, platinum, and irinotecan followed by third-line taxane-based therapy (p = 0.894).
In patients with MGC receiving third-line chemotherapy, TF1T3 was the only significant factor associated with OS. The sequence of using taxane and irinotecan as subsequent therapy after first-line failure was not shown to impact survival outcome.
Although the incidence of gastric cancer (GC) has been declining over the past several decades, it remains the third most common cause of cancer death worldwide . In Korea, GC has the second highest incidence of all cancers and it is the third leading cause of cancer death . For patients with metastatic or recurrent GC, palliative chemotherapy prolongs overall survival (OS) and provides significant palliation of symptoms compared to the best supportive care (BSC) alone [3–5]. Although fluoropyrimidine and platinum combination chemotherapy is widely recognized as the standard first-line treatment, the median progression-free survival (PFS) has been reported to be 4–7 months, and nearly all patients will eventually develop progressive disease following first-line chemotherapy [6–10]. Several recent phase III studies have shown that second-line chemotherapy provides an improvement in OS when compared to BSC [11–15]. In these studies, three cytotoxic chemotherapeutic agents (paclitaxel, docetaxel, and irinotecan) and one anti-vascular endothelial growth factor receptor antibody (ramucirumab) were shown to be associated with significant reductions in the risk of death. Therefore, second-line chemotherapy is currently considered the standard of care in patients with metastatic or recurrent GC after first-line failure. Nevertheless, many patients receiving second-line treatment fail to achieve response and even in responders, the duration of response is as short as a few months. While it is common practice to offer further lines of chemotherapy after second-line failure, especially in Eastern Asian countries, there is limited data on the efficacy of third-line chemotherapy in patients with metastatic or recurrent GC. Since some patients with good performance status (PS) are candidates for and may benefit from third-line therapy, it is essential to identify the subset of patients with the greatest likelihood of benefitting from third-line chemotherapy.
To date, only a few studies have focused on third-line chemotherapy; therefore, data on third-line chemotherapy in patients with metastatic or recurrent GC are inconclusive [17–21]. In addition, the majority of these studies have been small phase II studies or retrospective studies that have evaluated the efficacy and safety of monotherapy or combinations of several cytotoxic agents. One study using various regimens as the third-line therapy reported a median PFS and OS of 2.6 and 6.4 months, respectively, and a response rate of 10.3% . In small phase II studies of paclitaxel  or docetaxel [19, 20], response rates were in the range of 15–23%, with a median OS of 4–7 months. In another retrospective study of 158 patients, Kang et al. reported the efficacy and safety of third-line irinotecan and 5-fluorouracil (FOLFIRI) combination chemotherapy: median PFS and OS were 2.1 and 5.6 months, respectively, with tolerable toxicity profiles . In real-world clinical practice, some patients who have a good PS after first- and second-line failure continue on to receive third-line chemotherapy; both F, P, and T followed by third-line I-based therapy or F, P, and I followed by third-line T-based therapy are common clinical practice patterns.