Abstract 1300P
Background
Pancreatic cancer (PC) is the 4th leading cause of cancer deaths, with a 5-year survival of only 11%. FOLFIRINOX (FX) or gemcitabine with albumin-bound paclitaxel (GP) are standard in the first line (1L) setting, though no biomarkers are available to guide therapy selection. Since FX is platinum (Pt) containing and homologous recombination deficiency (HRD) is a biomarker of Pt response in other tumors, we examined whether HRD is associated with FX benefit.
Methods
This study used the nationwide (US-based, ∼280 US cancer clinics) de-identified Flatiron Health-Foundation Medicine PC clinico-genomic database (FH-FMI CGDB). Outcomes of 1149 evaluable metastatic PC patients (pts) treated with 1L FX or GP were examined. HRDsig was called using a machine learning based algorithm (AACR 2022 #1249). Real-world overall survival (rwOS) and time to next treatment (TTNT), accounting for left-truncation from start of 1L, were estimated using Kaplan-Meier analysis. Cox proportional hazards models were adjusted (aHR) for age, surgery, ECOG, CA19-9, and tissue type with random sample imputation for missing clinical values.
Results
HRDsig(+) was observed in 9% (94/1081) of PC pts. 52% received FX and 48% GP in the 1L setting. Overall median rwOS for FX and GP was 6.9 and 5.1 mo. FX treated pts with HRDsig(+) had better rwOS and TTNT compared to those with HRDsig(-) (median rwOS 14.8 vs 6.3 mo; aHR: 0.50 (0.34 – 0.73), p <0.001; median TTNT 8.5 vs 5.3 mo; aHR: 0.54 (0.39 – 0.76), p < 0.001). rwOS at 1- and 2-years was 58% and 25% in FX-treated HRDsig(+) pts, relative to 21% and 2% in GP-treated HRDsig(+) pts. Minimal differences were observed in rwOS for HRDsig(-) pts treated with FX and GP (median 6.3 v 5.1 mo). HRDsig was trending predictive in patients harboring BRCA1/2/PALB2 alterations (FX median rwOS 17.0 v 12.1 mo in HRDsig(+) v HRDsig(-), aHR: 0.19 (0.02 – 1.72), p =0.14) and predictive in patients wildtype for BRCA1/2/PALB2 (FX rwOS 10.6 v 6.1 mo in HRDsig(+) v HRDsig(-), aHR: 0.35 (0.15 – 0.81), p =0.014).
Conclusions
Using a real-world clinical dataset, we found that HRDsig positivity was predictive of FX benefit in metastatic PC. Additional studies are warranted to further explore the utility of this biomarker.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T. Chen: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. R.W. Madison: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. N. Bhardwaj: Financial Interests, Full or part-time Employment: Foundation Medicine, Roche. D.X. Jin: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. Z. Fleischmann: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. J. Newberg: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. J. Moore: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. G.M. Frampton: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Ownership Interest: Roche. P. Hegde: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. D.A. Fabrizio: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. J. He: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. A.B. Schrock: Financial Interests, Full or part-time Employment: Foundation Medicine; Financial Interests, Stocks/Shares: Roche. E. Ebot: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Ownership Interest: Roche. E.S. Sokol: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. All other authors have declared no conflicts of interest.