Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B)

Abstract

Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.

Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.

Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55-1.17) and 0.55 for PFS (95% CI 0.38-0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42-1.29) and 0.79 for PFS (95% CI 0.42-1.49).

Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC.

Keywords: Biliary tract cancer; Chemotherapy; Older; Survival; Unresectable.

Fig. 1

Overall survival (A) and progression-free survival (B) according to first-line chemotherapy. The blue, yellow, grey, orange, and pale blue lines represent the gemcitabine + cisplatin + S-1, gemcitabine + cisplatin, gemcitabine + S-1, gemcitabine monotherapy, and S-1 monotherapy groups, respectively

Fig. 2

Comparison of overall survival (A) and progression-free survival (B) between gemcitabine + cisplatin + S-1 and gemcitabine + cisplatin groups using propensity-score-matched analysis. The blue and orange line represents gemcitabine + cisplatin + S-1 and gemcitabine + cisplatin groups, respectively

Fig. 3

Comparison of overall survival (A) and progression-free survival (B) between gemcitabine + cisplatin and gemcitabine monotherapy groups using propensity-score-matched analysis. The blue and orange line represents gemcitabine + cisplatin and gemcitabine monotherapy groups, respectively