Impact of tumor shrinkage pattern by biweekly triplet gemcitabine/cisplatin/s-1 for biliary tract cancers: Implication for neoadjuvant therapy (KHBO1401-1A study).

Abstract

4093 Background: There have not been any new evidenced regimen for biliary tract cancers (BTC) after ABC-02 study, we conducted biweekly triplet gemcitabine/cisplatin/s-1 regimen (GCS) and compared with conventional doublet gemcitabine/cisplatin regimen (GC) as phase III (KHBO1401) study. Biweekly GCS was proved not only to prolong patients’ survival (HR 0.791 (90% C.I. 0.628-0.996), one-sided P = 0.046) but also to achieve high response rate (42% versus 15%, P < 0.001) and good conversion rate (2.5% versus 0.0%), and would be good for neoadjuvant therapy. Herein, we investigated tumor shrinkage pattern to explore possibilities of neoadjuvant therapy. Methods: Totally 246 patients were enrolled in multi-center phase III KHBO1401 study between 2014 and 2016. Tumor shrinkage pattern (best response, timing, response at 100 days (14 weeks, approx. 6 cycles in GCS and 4 cycles in GC), etc.) and survival were investigated in the patients with measurable BTC (n = 183, 74%, 91 in GCS and 92 in GC) as sub-analysis. P < 0.05 was considered statistically significant. Results: Tumor shrinkage pattern could be divided to 4 categories by the response at 100 days after enrollment; category A ( < -30% in size), B (-30% to 0%), C (0% to +20%), and D ( > +20%). GCS arm contained more category A & B (61 (67%) vs. 33 (36%), P < 0.0001). Each category predicted best response and overall survival (p < 0.0001). Timing for maximum tumor response were different among categories, category A achieved maximum tumor shrinkage at 165 +/- 76 days in GCS and 225 +/- 190 days in GC, category B at 139 +/- 78 versus 154 +/- 82 days, and category C and D did not achieve tumor shrinkage. Maximum tumor shrinkage in category A was -53% in GCS versus -65% in GC (P = 0.0892), and 20% patients in GCS underwent tumor regrowth 154 +/- 143 days later. Conclusions: GCS provided faster and more tumor shrinkage with better survival in the comparison of GC, although it had 20% risk of re-growth after 6 cycles.