Correlation of multiple endpoints in the first-line chemotherapy of advanced gastric cancer: Pooled analysis of individual patient data from Japanese Phase III trials.

Background: Individual-level surrogates are important for management in patients treated for advanced gastric cancer (AGC). This study aimed to comprehensively investigate the correlation of multiple clinical endpoints in the first-line chemotherapy of AGC.

Methods: Individual patient data (IPD) were collected from four Japanese Phase III trials comparing S-1-based first-line chemotherapies (SPIRITS, START, GC0301/TOP-002, and G-SOX trials). Patients without Response Evaluation Criteria in Solid Tumors (RECIST)-based radiological assessments were excluded. Spearman's rank correlation coefficient was tested for correlation among overall survival (OS), progression-free survival (PFS), and postprogression survival (PPS). OS, PFS, and PPS were compared between responders (best response: complete response or partial response) and nonresponders (best response: stable disease or progressive disease).

Results: The study included a total of 1492 patients. Eighty percent of the patients (n = 1190) received subsequent chemotherapies after the failure of each trial's treatment protocol. PFS moderately correlated with OS (Spearman correlation coefficient = 0.66, p < 0.005), whereas the correlation between PPS and OS was strong (Spearman correlation coefficient = 0.87, p < 0.005). Responders had significantly longer OS (median, 17.7 vs. 9.1 months, p < 0.005), PFS (median, 6.9 vs. 2.8 months, p < 0.005), and PPS (median, 10.5 vs. 6.0 months, p < 0.005) than nonresponders.

Conclusions: Our results reacknowledged the mild surrogacy of PFS and importance of postprogression treatments in patients with AGC receiving first-line chemotherapy. Consistent longer survival outcomes in better RECIST categories suggested that tumor response might be a useful individual-level surrogate.