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Published in: Annals of Surgical Oncology 5/2023

14-02-2023 | Computed Tomography | Pancreatic Tumors

CA19-9 Response to First-Line Neoadjuvant FOLFIRINOX and Second-Line Gemcitabine/Nab-Paclitaxel for Patients with Operable Pancreatic Cancer

Authors: Sam Z. Thalji, MD, Mandana Kamgar, MD, MPH, Ben George, MD, Mohammed Aldakkak, MD, Kathleen K. Christians, MD, Callisia N. Clarke, MD, MS, Beth A. Erickson, MD, William A. Hall, MD, Parag P. Tolat, MD, Zachary L. Smith, DO, Douglas B. Evans, MD, Susan Tsai, MD, MHS

Published in: Annals of Surgical Oncology | Issue 5/2023

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Abstract

Background

Response to second-line (2L) neoadjuvant therapy for operable pancreatic cancer (PC) is understudied. This study examined carbohydrate antigen 19-9 (CA19-9) response to first-line (1L) and 2L chemotherapy.

Methods

The study identified patients with operable PC and elevated CA19-9 (≥ 35 U/mL with total bilirubin < 2 mg/dL) who received 1L FOLFIRINOX (FFX). The patients were restaged after 2 months and based on response, received additional FFX or gemcitabine/nab-paclitaxel (GnP) as part of total neoadjuvant therapy. Response was defined as a decrease in tumor size on computed tomography (CT) imaging or a decline in CA19-9 of 50% or more and preserved performance status.

Results

For operable PC with an elevated CA19-9, 108 patients received 1L FFX. After 2 months of chemotherapy, the decision was made to continue FFX (FFX ≥ FFX) for 76 (70%) of the 108 patients and switch to GnP (FFX ≥ GnP)) for 32 (30%) of the patients. Of the 32 FFX ≥ GnP patients, 27 had no evidence of radiographic or biochemical (CA19-9) response to 1L FFX. Of these 27 patients, 26 (96%) demonstrated a response to 2L GnP. After 4 months of chemotherapy, 62 (82%) of the 76 FFX ≥ FFX patients had a CA19-9 response compared with 31 (97%) of the 32 FFX ≥ GnP patients (p = 0.04).

Conclusions

Lack of biochemical response to 2 months of 1L FFX may identify a subgroup of patients with a very high rate of response to 2L GnP, emphasizing the importance of assessing treatment response at 2-month intervals.
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Literature
2.
go back to reference Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–7.CrossRefPubMedPubMedCentral Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–7.CrossRefPubMedPubMedCentral
3.
go back to reference Tsai S, Christians KK, George B, Ritch PS, Dua K, Khan A, et al. A phase II clinical trial of molecular profiled neoadjuvant therapy for localized pancreatic ductal adenocarcinoma. Ann Surg. 2018;268:610–9.CrossRefPubMed Tsai S, Christians KK, George B, Ritch PS, Dua K, Khan A, et al. A phase II clinical trial of molecular profiled neoadjuvant therapy for localized pancreatic ductal adenocarcinoma. Ann Surg. 2018;268:610–9.CrossRefPubMed
4.
go back to reference Versteijne E, et al. Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the Dutch randomized PREOPANC trial. J Clin Oncol. 2022;40(11):1220–30 Versteijne E, et al. Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the Dutch randomized PREOPANC trial. J Clin Oncol. 2022;40(11):1220–30
5.
go back to reference Ahmad SA, Duong M, Sohal DPS, Gandhi NS, Beg MS, Wang-Gillam A, et al. Surgical outcome results from SWOG S1505. Ann Surg. 2020;272:481–6.CrossRefPubMed Ahmad SA, Duong M, Sohal DPS, Gandhi NS, Beg MS, Wang-Gillam A, et al. Surgical outcome results from SWOG S1505. Ann Surg. 2020;272:481–6.CrossRefPubMed
6.
go back to reference Macedo FI, Ryon E, Maithel SK, Lee RM, Kooby DA, Fields RC, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270:400–13.CrossRefPubMed Macedo FI, Ryon E, Maithel SK, Lee RM, Kooby DA, Fields RC, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270:400–13.CrossRefPubMed
7.
go back to reference Perri G, Prakash L, Qiao W, Varadhachary GR, Wolff R, Fogelman D, et al. response and survival associated with first-line FOLFIRINOX vs gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma. JAMA Surg. 2020;155:832–9.CrossRefPubMedPubMedCentral Perri G, Prakash L, Qiao W, Varadhachary GR, Wolff R, Fogelman D, et al. response and survival associated with first-line FOLFIRINOX vs gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma. JAMA Surg. 2020;155:832–9.CrossRefPubMedPubMedCentral
8.
go back to reference Grose DB, McKay CJ, Cooke S, Graham JS, Duthie F, Jamieson N, et al. PRIMUS-002: a multicentre, open-label, phase II study examining FOLFOX and nab-paclitaxel (FA) and nab-paclitaxel and gemcitabine (AG) as neoadjuvant therapy for (borderline) resectable pancreatic cancer (PC), focusing on biomarker and liquid biopsy development. J Clin Oncol. 2019;37:TPS4166.CrossRef Grose DB, McKay CJ, Cooke S, Graham JS, Duthie F, Jamieson N, et al. PRIMUS-002: a multicentre, open-label, phase II study examining FOLFOX and nab-paclitaxel (FA) and nab-paclitaxel and gemcitabine (AG) as neoadjuvant therapy for (borderline) resectable pancreatic cancer (PC), focusing on biomarker and liquid biopsy development. J Clin Oncol. 2019;37:TPS4166.CrossRef
9.
go back to reference Portal A, Pernot S, Tougeron D, Arbaud C, Bidault AT, de la Fouchardière C, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after FOLFIRINOX failure: an AGEO prospective multicentre cohort. Br J Cancer. 2015;113:989–95.CrossRefPubMedPubMedCentral Portal A, Pernot S, Tougeron D, Arbaud C, Bidault AT, de la Fouchardière C, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after FOLFIRINOX failure: an AGEO prospective multicentre cohort. Br J Cancer. 2015;113:989–95.CrossRefPubMedPubMedCentral
10.
go back to reference Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed
14.
go back to reference Tsai S, et al. Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer. Ann Surg. 2020;271:740–7.CrossRefPubMed Tsai S, et al. Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer. Ann Surg. 2020;271:740–7.CrossRefPubMed
15.
go back to reference Macedo FI, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270:400–13.CrossRefPubMed Macedo FI, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270:400–13.CrossRefPubMed
16.
19.
go back to reference Ferrone CR, et al. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.CrossRefPubMed Ferrone CR, et al. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.CrossRefPubMed
22.
go back to reference Katz MH, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118:5749–56.CrossRefPubMed Katz MH, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118:5749–56.CrossRefPubMed
23.
go back to reference Maggino L, et al. Outcomes of primary chemotherapy for borderline resectable and locally advanced pancreatic ductal adenocarcinoma. JAMA Surg. 2019;154:932–42.CrossRefPubMedPubMedCentral Maggino L, et al. Outcomes of primary chemotherapy for borderline resectable and locally advanced pancreatic ductal adenocarcinoma. JAMA Surg. 2019;154:932–42.CrossRefPubMedPubMedCentral
24.
go back to reference Walma MS, et al. Treatment strategies and clinical outcomes in consecutive patients with locally advanced pancreatic cancer: a multicenter prospective cohort. Eur J Surg Oncol. 2021;47(3 Pt B):699–707.CrossRefPubMed Walma MS, et al. Treatment strategies and clinical outcomes in consecutive patients with locally advanced pancreatic cancer: a multicenter prospective cohort. Eur J Surg Oncol. 2021;47(3 Pt B):699–707.CrossRefPubMed
25.
go back to reference Gilabert M, et al. Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with advanced pancreatic adenocarcinoma. Medicine United States. 2017;96:e6544. Gilabert M, et al. Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with advanced pancreatic adenocarcinoma. Medicine United States. 2017;96:e6544.
26.
go back to reference Truty MJ, et al. Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer. Ann Surg. 2021;273:341–9.CrossRefPubMed Truty MJ, et al. Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer. Ann Surg. 2021;273:341–9.CrossRefPubMed
27.
go back to reference Janssen QP, et al. Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial. BMC Cancer. 2021;21:300.CrossRefPubMedPubMedCentral Janssen QP, et al. Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial. BMC Cancer. 2021;21:300.CrossRefPubMedPubMedCentral
28.
go back to reference Katz MHG, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017;17:505.CrossRefPubMedPubMedCentral Katz MHG, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017;17:505.CrossRefPubMedPubMedCentral
29.
go back to reference Bailey P, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47–52.CrossRefPubMed Bailey P, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47–52.CrossRefPubMed
31.
go back to reference Moffitt RA, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47:1168–78.CrossRefPubMedPubMedCentral Moffitt RA, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47:1168–78.CrossRefPubMedPubMedCentral
32.
go back to reference Aung KL, et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res. 2018;24:1344–54.CrossRefPubMed Aung KL, et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res. 2018;24:1344–54.CrossRefPubMed
33.
go back to reference Rashid NU, et al. Purity independent subtyping of tumors (PurIST), a clinically robust, single-sample classifier for tumor subtyping in pancreatic cancer. Clin Cancer Res. 2020;26:82–92.CrossRefPubMed Rashid NU, et al. Purity independent subtyping of tumors (PurIST), a clinically robust, single-sample classifier for tumor subtyping in pancreatic cancer. Clin Cancer Res. 2020;26:82–92.CrossRefPubMed
34.
go back to reference Luo G, et al. Patients with normal-range CA19-9 levels represent adistinct subgroup of pancreatic cancer patients. Oncol Lett. 2017;13:881–6.CrossRefPubMed Luo G, et al. Patients with normal-range CA19-9 levels represent adistinct subgroup of pancreatic cancer patients. Oncol Lett. 2017;13:881–6.CrossRefPubMed
35.
go back to reference Vestergaard EM, et al. Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem. 1999;45:54–61.PubMed Vestergaard EM, et al. Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem. 1999;45:54–61.PubMed
Metadata
Title
CA19-9 Response to First-Line Neoadjuvant FOLFIRINOX and Second-Line Gemcitabine/Nab-Paclitaxel for Patients with Operable Pancreatic Cancer
Authors
Sam Z. Thalji, MD
Mandana Kamgar, MD, MPH
Ben George, MD
Mohammed Aldakkak, MD
Kathleen K. Christians, MD
Callisia N. Clarke, MD, MS
Beth A. Erickson, MD
William A. Hall, MD
Parag P. Tolat, MD
Zachary L. Smith, DO
Douglas B. Evans, MD
Susan Tsai, MD, MHS
Publication date
14-02-2023
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 5/2023
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-022-13055-1

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