Efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient advanced pancreatic adenocarcinoma: an AGEO European Cohort.

BACKGROUND

Immune checkpoint inhibitors (ICIs) improve oncological outcomes in patients with microsatellite instability-high (MSI) or mismatch repair-deficient (dMMR) advanced solid tumours. Nevertheless, based on limited published data, the outcome of patients with MSI/dMMR pancreatic ductal adenocarcinoma (PDAC) seems poorer when compared to other malignancies. This multi-institutional analysis sought to assess the efficacy and tolerability of ICIs in a large real-world cohort of patients with MSI/dMMR PDAC.

METHODS

We retrospectively collected data from patients with MSI/dMMR advanced PDAC treated with ICIs in 16 centers. Progression-free survival and overall survival were calculated from the start of treatment, and we report objective response and disease control rates according to RECIST V1.1.

RESULTS

Thirty-one MSI/dMMR advanced PDAC patients were identified. Twenty-five patients received single-agent anti-PD-1 antibodies, three patients received the combination of nivolumab and ipilimumab and three patients received immunotherapy in combination with chemotherapy. Among 31 evaluable patients, 15 (48.4%) had an objective response (three complete responses and 12 partial responses), and six (19.4%) had stable disease. With a median follow-up of 18 months, the median progression-free survival (PFS) was 26.7 months and the median overall survival (OS) was not reached. Disease control rates (DCRs) among patients with only one line of prior therapy (N = 17) was 76.5%. Grade 3-4 treatment-related adverse events were not observed.

CONCLUSION

This retrospective analysis suggests that ICIs are effective and well tolerated in patients with MSI/dMMR advanced PDAC. Hence, our work supports the use of PD-1 inhibition in this group of patients with high unmet medical need.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julien Taïeb has received honoraria as a speaker or in an advisory role from Sanofi, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, Lilly, AstraZeneca, and MSD. Kathrin Heinrich has received honoraria from Roche and Taiho, has served in a consulting or advisory role for BMS, Servier, and has received travel support from Amgen, Merck, and Servier. Volker Kunzmann has received grants and honoraria as a speaker or in an advisory role from Amgen, AstraZeneca, BMS, and MSD. Alice Boileve has received support for travel to meetings from Merck and Ipsen. Sara Lonardi has received personal fees for scientific consultancy for Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, Incyte, Lilly, Merck Serono, MSD, and Servier, and as an invited speaker from Amgen, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre-Fabre, Roche, and Servier. Benoist Chibaudel has received honoraria as a speaker or in an advisory role from Amgen, Bayer, Beigine, Biocartis, BMS, Lilly, MSD, Pfizer, Pierre Fabre, Roche, Sanofi, SeqOne, Servier, and Takeda. Anthony Turpin has received honoraria as a speaker or in an advisory role from Merck Serono, Servier, BMS, Pierre Fabre, Lilly, AstraZeneca, Viatris, and MSD. Vincent Hautefeuille has received honoraria as a speaker or in an advisory role from Amgen, Merck, Deciphera, AAA, Ipsen, Servier, and Pierre Fabre. – Caterina Vivaldi has received honoraria as a speaker or in an advisory role from Roche, Bayer, Taiho, and Terumo. Thibault Mazard has received honoraria from Servier, Pierre Fabre, Merck Serono, AAA and Sanofi, a research grant from Amgen, and support for attending meetings from Pierre Fabre, Merck Serono and Sanofi. Monica Niger has received speaker honoraria from Accademia della Medicina and Incyte, honoraria from Sandoz, Medpoint SRL, and Servier for editorial collaboration, and consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, AstraZeneca and Taiho. Gerald W. Prager has received honoraria as a speaker or in an advisory role from Roche, Merck Serono, Amgen, Servier, Bayer, BMS, Pierre Fabre, Lilly, Daiichy Sanyo, AstraZeneca, and MSD. Clelia Coutzac has received honoraria as a speaker or in an advisory role from Amgen, Servier, and Merck Serono. C. Benedikt Westphalen has received honoraria from Amgen, Bayer, BMS, Chugai, Celgene, Falk, GSK, MSD, Merck, Janssen, Ipsen, Roche, Servier, SIRTeX, and Taiho, has served on advisory boards for Bayer, BMS, Celgene, Janssen, MSD, Servier, Shire/Baxalta, Rafael Pharmaceuticals, RedHill, and Roche, has received travel support from Bayer, Celgene, Janssen, RedHill, Roche, Servier, and Taiho and research grants (institutional) from Roche. CBW serves as an officer for the European Society of Medical Oncology (ESMO), Deutsche Krebshilfe (DKH), Arbeitsgemeinschaft internistische Onkologie (AIO) and is a member of the EU Commission expert group: Mission Board for cancer. Edouard Auclin has received honoraria from Amgen (Board), Sanofi (Board), and Institut Servier (Research Grant). Lorenzo Pilla, Lina Sayah, Geert Cirkel, Tamar Beller, and Lucile Bauguion have nothing to disclose.