Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113)

Abstract

Background: The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs).

Patients and methods: A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy [ICT; either nab-paclitaxel/gemcitabine alone or nab-paclitaxel/gemcitabine followed by FOLFIRINOX (combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin)] followed by surgical exploration of all patients without evidence of disease progression. CA 19-9 was determined at baseline and after ICT and correlated with overall survival (OS) and secondary R0 resection rate.

Results: From the NEOLAP study population (N = 165) 133 patients (81%) were evaluable for CA 19-9 at baseline and 81/88 patients (92%) for post-ICT CA 19-9 response. Median OS (mOS) in the CA 19-9 cohort (n = 133) was 16.2 months [95% confidence interval (CI) 13.0-19.4] and R0 resection (n = 31; 23%) was associated with a significant survival benefit [40.8 months (95% CI 21.7-59.8)], while R1 resected patients (n = 14; 11%) had no survival benefit [14.0 (95% CI 11.7-16.3) months, hazard ratio (HR) 0.27; P = 0.001]. After ICT most patients showed a CA 19-9 response (median change from baseline: -82%; relative decrease ≥55%: 83%; absolute decrease to ≤50 U/ml: 43%). Robust CA 19-9 response (decrease to ≤50U/ml) was significantly associated with mOS [27.8 (95% CI 18.4-37.2) versus 16.5 (95% CI 11.7-21.2) months, HR 0.49; P = 0.013], whereas CA 19-9 baseline levels were not prognostic for OS. Multivariate analysis demonstrated that a robust CA 19-9 response was an independent predictive factor for R0 resection. Using a CA 19-9 decrease to ≤61 U/ml as optimal cut-off (by receiver operating characteristic analysis) yielded 72% sensitivity and 62% specificity for successful R0 resection, whereas CA 19-9 nonresponders (<20% decrease or increase) had no chance for successful R0 resection.

Conclusions: CA 19-9 response after multiagent ICT provides relevant prognostic and predictive information and is useful in selecting LAPC patients for explorative surgery.

Clinical trial number: ClinicalTrials.govNCT02125136; https://ichgcp.net/clinical-trials-registry/NCT02125136; EudraCT 2013-004796-12; https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results.

Keywords: CA 19-9; NEOLAP; R0 resection rate; locally advanced pancreatic cancer; multiagent induction chemotherapy.

Conflict of interest statement

Disclosure IH reports honoraria from Celgene/BMS and Roche. JTS reports honoraria from AstraZeneca, Bayer, Celgene/BMS, MorphoSys, Roche, and Shire. EG reports honoraria from AstraZeneca, Celgene/BMS, MSD, Sanofi, and Servier. GS reports grants and honoraria from AstraZeneca, AURIKAMED, BeiGene, Eisai, Celgene/BMS, Deutsche Röntgengesellschaft, Isofol Medical, Janssen-Cilag, Lilly, Medizinwelten-Services GmbH, MOLOGEN, Novartis, Nutricia, Roche, Sanofi, Servier, and Shire. UMM reports honoraria from Amgen, Celgene/BMS, Lilly, Pierre-Fabre, Roche, and Sanofi. DW reports grants and honoraria from AstraZeneca, Bayer, Celgene/BMS, Eisai, Falk, Incyte, Ipsen, Novartis, Roche, Servier, Shire, and Sirtex. MF reports honoraria from Celgene/BMS, Falk, MSD, Roche and Servier. FK reports grants and honoraria from Celgene/BMS. SB reports grants and honoraria from Astra-Zeneca, Celgene/BMS, Fresenius, Incyte, Janssen-Cilag and Servier. TJE reports honoraria from Astra-Zeneca, Bayer, Celgene/BMS, Ipsen, Lilly, MSD, Roche, and Servier. RK reports employment by AIO-Studien-gGmbH. FA reports grants from the Interdisciplinary Center for Clinical Research (IZKF) Würzburg, Germany. AS reports grants from Deutsche Krebsgesellschaft (DKG). VH reports grants, honoraria, and nonfinancial support from Amgen, Astra-Zeneca, Baxalta, Boehringer-Ingelheim, Celgene/BMS, Halozyme, Lilly, Merck, MSD, Novartis, OncoSil, Pierre-Fabre, Roche, Sanofi, Servier, Shire, Sirtex, Taiho, and Terumo. VK reports grants and honoraria from Amgen, Astra-Zeneca, Celgene/BMS, MSD, and Servier. All remaining authors have declared no conflicts of interest.

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Kaplan–Meier curves. (A) Overall survival by resection status for nonresected (green), R1-resected (red), and R0-resected (blue) patients. (B) Overall survival by CA 19-9 response for patients with CA 19-9 response to ≤50 U/ml (blue) and >50 U/ml (red). CI, confidence interval; HR, hazard ratio.