Adjuvant mFOLFIRINOX (mFFX) for resected pancreatic cancer (PC): Long term clinical and genomic outcomes.

person Fergus Keane Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland info_outline Fergus Keane, Drew Moss, Catherine A O'Connor, Maria Perry, Joanne F. Chou, Fionnuala Crowley, Parima Saxena, Amelia Chan, Wungki Park, Anna M. Varghese, Kenneth H. Yu, Marinela Capanu, T. Peter Kingham, Michael Ian D'Angelica, Vinod P. Balachandran, William R. Jarnagin, Alice C Wei, Kevin Soares, Fiyinfolu Balogun, Eileen M. O'Reilly

Authors person Fergus Keane Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland info_outline Fergus Keane, Drew Moss, Catherine A O'Connor, Maria Perry, Joanne F. Chou, Fionnuala Crowley, Parima Saxena, Amelia Chan, Wungki Park, Anna M. Varghese, Kenneth H. Yu, Marinela Capanu, T. Peter Kingham, Michael Ian D'Angelica, Vinod P. Balachandran, William R. Jarnagin, Alice C Wei, Kevin Soares, Fiyinfolu Balogun, Eileen M. O'Reilly Organizations Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland, Icahn School of Medicine at Mount Sinai Morningside-West, New York, NY, Memorial Sloan Kettering Cancer Center, New York, NY, Mount Sinai Hospital, New York, NY, SUNY Downstate, Brooklyn, NY, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY Abstract Disclosures Research Funding No funding sources reported Background: Adjuvant chemotherapy with mFFX is the standard for pts with ECOG 0-1 (1) after pancreatectomy for resectable PC. Herein, we report long-term survival data on an expanded cohort and present comprehensive genomic analyses. Methods: Pts with resected PC who received >1 dose of adjuvant mFFX identified from institutional databases. Primary endpoints: Recurrence Free Survival (mRFS) and Overall Survival (mOS) calculated from start of treatment until recurrence or death. Key secondary endpoints: clinical factors, genomic descriptors ( KRAS status, whole genome doubling (WGD), and homologous recombination deficiency (HRD)) associated with outcome. Kaplan-Meier method used to estimate RFS and OS. Univariate Cox proportional hazards model correlated clinico-genomic characteristics with RFS and OS. Results: N=147 identified between 01/2015-01/2022. Median age: 67 years; N= 22 (15%) > 75 years. Several prognostically unfavorable groups; N=52 (36%) stage III disease/ N2 nodal status; N=115 (78%) lymphovascular invasion (LVI); N=133 (90%) perineural invasion (PNI). Median time from surgery to start mFFX: 1.78m (IQR; 1.45, 2.12). Median CA 19-9 at start mFFX: 21 (range 0-1,124). N=124 (84%) pts completed 12 doses mFFX (+/- 12 doses oxaliplatin). N=98 pts (67%) stopped oxaliplatin early for neuropathy. With the median follow up 35.1m (range 5.1, 73.0), mRFS 27m (95% CI 20, 39) and OS not reached (NR). For >75 cohort, mRFS 12m (95% CI 9.6, NR) and mOS 30m (95% CI 19, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p= 0.033) and OS (HR 0.53; 95% CI 0.3, 0.94; p= 0.030). T3 tumors associated with worse RFS (HR 2.82, 95% CI 1.28, 6.20; p=0.010) and OS (HR 5.10, 95% CI 1.45, 18; p=0.011). Genomic variables summarized (Table). KRAS mutation (+), WGD (+), and higher KRAS CNV trended to shorter RFS and OS; statistical significance limited by small subgroups. HRD status did not confer differences in OS. Conclusions: Adjuvant mFFX is an effective therapy and results in long-term OS outcome in resected PC in a non-trial setting, including for pts >75 years. Early initiation of adjuvant mFFX may optimize outcome. Trends observed for improved outcome in select genomic subsets, which require large-scale validation. 1. Conroy, JAMA Onc, 2022. N=126 Somatic Testing; N=61 WGD Analysis 12 Month RFS (95% CI) 24 Month RFS (95% CI) 12 Month OS (95% CI) 24 Month OS (95% CI) KRAS mutated (N=115) vs wildtype (N=12) 67% (58, 76) vs 75% (54, 100) 46% (37, 57) vs 75% (54, 100) 97% (94, 100) vs 83% (65, 100) 77% (69, 85) vs 83% (65, 100) HRD Status (Core (N=9) vs Non-core (N=16) vs no variant (N=101)) 56% (31, 100) vs 69% (49, 96) vs 68% (60, 78) 44% (21, 92) vs 50% (31, 82) vs 49% (40, 60) 89% (71, 100) vs 100% (100, 100) vs 96% (92, 100) 89% (71, 100) vs 73% (53, 100) vs 77% (69, 86) WGD +ve (N=6) vs WGD -ve (N=55) 50% (22, 100) vs 65% (53, 80) 17% (2.8, 100) vs 39% (27, 55) 100% (100, 100) vs 98% (94, 100) 50% (22, 100) vs 79% (68, 91)