Impact of Tumor Shrinkage Pattern with Biweekly Triplet Gemcitabine+Cisplatin+S-1 Regimen for Biliary Tract Cancers: Implications for Neoadjuvant Therapy from the Data of KHBO1401 (KHBO1401-1A Study)

Abstract

<b><i>Introduction:</i></b> The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] vs. GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. <b><i>Methods:</i></b> Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (<i>n</i> = 183, 74%; GCS, <i>n</i> = 91; GC, <i>n</i> = 92). <b><i>Results:</i></b> The tumor shrinkage pattern could be divided into 4 categories based on the response at 100 days after enrollment: categories A (&lt;–30% in size), B (−30–0%), C (0% to +20%), and D (&gt;+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], <i>p</i> &lt; 0.0001). Each category predicted the best response and overall survival (<i>p</i> &lt; 0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was −53% in the GCS arm and −65% in the GC arm (<i>p</i> = 0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. <b><i>Conclusion:</i></b> GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed regrowth after 6 cycles.