The role of third-line chemotherapy in recurrent or metastatic gastric cancer A cohort study with propensity score matching analysis

In recurrent or metastatic gastric cancer, second-line chemotherapy is generally recommended in current guidelines. Although third-line therapy is often performed in daily practice in some countries, there are only a few reports about its benefits. A retrospective review was conducted on 682 patients who underwent at least first-line chemotherapy for recurrent (n=297) or primary metastatic (n=385) disease. Clinicopathological characteristics and overall survival (OS) were analyzed according to lines of chemotherapy. One hundred sixty-seven patients (24.5%) underwent third- or further-line therapy. Third- or further-line therapy was frequently performed in patients with young age (<70) (P<.0001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (P<.0001), surgical resection before first-line therapy (P=.007), and first-line combination regimen (P=.001). The median OS for all patients after the initiation of first-line therapy was 10 months. The median OS of patients who received third- or further-line therapy was significantly longer than that of patients who received second-or lesser-line therapy (18 vs 8 months, P<.0001). The multivariate analysis revealed that third- or further-line therapy was independently associated with favorable OS (hazard ratio=0.58, P<.0001). Moreover, patients who received third- or further-line therapy demonstrated better OS both in univariate (P=.002) and multivariate (P<.0001) analysis even after propensity score matching using baseline characteristics. The median OS after the start of third- line chemotherapy was 6 months. In addition, ECOG PS 0 or 1 at the initiation of third- line therapy (P<.0001) and surgical resection (P=.009) were independently associated with longer OS after third- line therapy. The current study suggests that third- line therapy could be recommended for recurrent or metastatic gastric cancer patients with good PS after progression from second-line chemotherapy in clinical practice.