Alternating neoadjuvant gemcitabine-nab-paclitaxel (GnP) and nal-irinotecan, 5-fluorouracil and folinic acid (nal-IRI) regimens in resectable (R) and borderline resectable (BR) pancreatic cancer (PC): A pilot study.

Abstract

706 Background: Alternating chemotherapy regimens in PC offers potential advantages of 1) toxicity mitigation 2) therapeutic enhancement and 3) flexibility of incorporation of additional therapeutic agents. Given previous success in alternating GnP and topoisomerase inhibitors in metastatic PC at our institution (Schroeder et.al. Cancers 10.3390/cancers 15235588 11/2023 ), we elected to test this approach in R and BR PC. Methods: Patients (pts) with de novo biopsy proven R or BR PC were study eligible. Key inclusion criteria were 1) ECOG PS 0/1 2) adequate hematological, hepatic, and renal function, 3) baseline neuropathy·≤ grade 1 4) dedicated CT imaging using pancreas protocol CT technique and 5) staging laparoscopy. All pts underwent laparoscopic staging. There was no CA 19.9 cutoff at study initiation. Chemotherapy (CTX) regimens were employed according to standard published dose and schedule. Neutrophil growth factors were not routinely used. Pts with R PC received 1 cycle each GnP/nal-IRI preop, then 2 cycles each. postop (6 cycles total). Pts with BR PC received 6 cycles alternating GnP/nal-IRI preop (2-2-1-1) followed by surgery. Pts were followed every 2 months with H/P,CBC, CMR, Ca 19.9, CT imaging for 2 months for 2 years, then 3-6 months thereafter. Results: 50 pts (30 R, 20 BR) were enrolled. Median age was 69 years. ECOG 0/1 was 86%/14%, median CA 19.9 at presentation was 173 IU/157 IU for R/BR pts respectively. Median f/u is 44 months. The only grade ≥3 toxicities across all pts >10% were neutropenia (56%) and diarrhea (28%). Grade ≥ 3 neurotoxicity was 2% (1/50 pts). No pts discontinued therapy due to drug toxicity. There were no significant toxicity differences between R and BR pts. For R pts, 30/30 (100%) completed 2 cycles preop CTX, 27/29 (93%) pts underwent surgical resection (1 pt current scheduled) and 18/27 pts (67%) completed all 6 cycles protocol-defined CTX (3 remain on therapy).2-year OS is 64%, median OS is 30.9 mo (95% CI 18.5-63.4 mo); For BR pts, 16/20 (80%) pts completed all 6 cycles protocol- defined CTX. 13/20 (65%) pts underwent surgical resection. 1-yr OS was 85%, median OS was 15 mo (95% CI 12.4-51.5mo). Median OS for resected pts was 34.9 mo (95% CI 21.7-51.5 mo), median OS for all pts was 26.4 mo (95% CI 15.1mo-44.7 mo). Conclusions: 1) Alternating GnP/Nal-IRI can be safely and successfully administered to a high fraction of pts with R/BR PC without growth factor support and without significant neurotoxicity. 2) The results presented here compare favorably with other large neoadjuvant CTX trials (e.g. SWOG 1505, ESPAC 5) in R/BR PC with respect to toxicity and survival. 3) Further exploration of alternating CTX regimens in localized PC is warranted. Clinical trial information: NCT03703063 .