Real-world survival differences in advanced biliary tract cancer patients with ctDNA detected IDH1 mutations and FGFR2 fusions receiving first-line gemcitabine-cisplatin with and without immunotherapy.

Abstract

548 Background: Comprehensive genomic profiling (CGP) is recommended for patients (pts) with metastatic BTC (mBTC) given its aggressive, heterogeneous disease profile. Liquid biopsy is a rapid, non-invasive option with high concordance to tissue-based CGP. First-line (1L) therapy in mBTC is gemcitabine-cisplatin (GemCis) +/- durvalumab or pembrolizumab (IO) regardless of CGP results. However, data suggests pts with targetable alterations may have worse outcomes with addition of IO compared to all comers. We examined outcomes for mBTC pts receiving 1L GemCis vs. GemCis+IO following ctDNA-detected IDH1 mutation ( IDH1 +) or FGFR2 fusion ( FGFR2 +). Methods: Real-world data was sourced from GuardantINFORM, which comprises aggregated commercial payer health claims and de-identified records from pts with clinical ctDNA testing via Guardant360 (G360). Pts with mBTC and >1 treatment claim after G360 results, and IDH+ or FGFR2+ between April 2019 and June 2024 were analyzed. Only pts treated with 1L GemCis +/- IO were included. Outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all in months with 95% confidence intervals. Log-rank test was used to compare Kaplan-Meier survival curves. Results: 412 pts were IDH1+ and 154 were FGFR2+ . In the IDH1 + cohort, 184 pts were treated with GemCis and 106 pts with GemCis+IO. Pts receiving GemCis demonstrated improved rwOS vs. GemCis+IO [27.2 (23.6-37.8) vs. 16 (13.6-19.9) mo.; HR=0.4 (95CI 0.27-0.59), p<0.001]; there was no difference in rwTTNT [13 (10.8-14.3) vs. 10 (8.4-12.3); HR=0.85(95CI 0.6-1.22), p=0.4] or rwTTD [4.8 (4.1-5.5) vs. 6.6 (4.7-8.1); HR=1.17 (95CI 0.9-1.5), p=0.25]. Similarly, in the FGFR2 + cohort, pts receiving GemCis + IO (n=44) had worse rwOS than pts on GemCis (n=70) [NR (15.6-NR) vs. 43 (34.2-2.1); HR=0.37(95CI 0.18-0.74), p=0.005], with no difference in rwTTNT [8.9 (4.89-NR) vs. 13.78 (7.42-NR); HR=0.63 (95CI 0.36-1.1), p=0.1] or rwTTD [5.0 (3.1-7.8) vs. 4.2 (3.5-5.5); HR=1.08 (95CI 0.72-1.6), p=0.7]. Among all mBTC pts receiving GemCis+IO (n=1113), non- IDH1 + pts (n=1007) had numerically better rwOS compared to IDH1 + pts (n=106) [18.6 (17.2-21.3) vs. 16.0 (13.6-19.);HR=0.76 (95CI 0.6-1.03), p=0.075]. No survival difference was observed between IDH1+ (n=184) and non- IDH1 + (n=2333) pts receiving GemCis [27.2 (23.6-37.8) vs. 26.2 (24.5-28.2); HR=1.08 (95CI 0.88-1.32), p=0.4]. Conclusions: Addition of IO to GemCis in IDH1 + and FGFR2 + mBTC pts resulted in decreased rwOS. This data supports ctDNA CGP to inform clinical decision-making prior to 1L as well as at progression. Further studies in clinical cohorts are needed to confirm these findings.