From the results of the SPIRITS trial, combination of S-1 and cisplatin has been recommended for current first-line chemotherapy for advanced gastric cancer. Thereafter, additional benefit of trastuzumab combined with a cisplatin and either fluorouracil or capecitabine regimen against HER2-positive gastric cancer has been confirmed from the results of international clinical trials (ToGA study). Becasue combination of S-1 and cisplatin is a standard therapy in Japan, several clinical trials of S-1 and cisplatin combined with trastuzumab are in progress.
The advantage of the second-line chemotherapy for advanced gastric cancer has not been established in Japan. The AIO group has reported that irinotecan as second-line chemotherapy significantly prolongs overall survival compared with best supportive care. In addition, from the results of stratified analysis of AVAGAST trials and JCOG, integral analysis supported the usefulness of second-line therapy. However, the optimal regimen for second-line treatment has not been established. The results of randomized phase III trials of irinotecan versus weekly paclitaxel (WJOG4007) and irinotecan versus irinotecan plus S-1 (JACCRO GC-05) are awaited. Currently, there is no promising molecular target drug for secondary treatment of advanced gastric cancer. A phase III trial to compare the mTOR inhibitor, everolimus, and BSC in patients with advanced gastric cancer after progression on one or two prior systemic chemotherapies has been carried out. Although everolimus significantly improved progression-free survival, it did not improve overall survival. Future analysis might provide us more information.