Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer

Patricia Martin-Romano; Samy Ammari; Yolla El-Dakdoukti; Capucine Baldini; Andreea Varga; Perrine Vuagnat; Eric Angevin; Rastislav Bahleda; Anas Gazzah; Stephane Champiat; Jean M. Michot; Sophie Postel-Vinay; Aurelien Marabelle; Jean C. Soria; Valerie Boige; David Malka; Michel Ducreux; Christophe Massard; Antoine Hollebecque

doi:10.1016/j.ejca.2020.06.030

Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer

Patricia Martin-Romano, Samy Ammari, Yolla El-Dakdoukti, Capucine Baldini, Andreea Varga, Perrine Vuagnat, Eric Angevin, Rastislav Bahleda, Anas Gazzah, Stephane Champiat, Jean M. Michot, Sophie Postel-Vinay, Aurelien Marabelle, Jean C. Soria, Valerie Boige, David Malka, Michel Ducreux, Christophe Massard, Antoine Hollebecque

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Background: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. Material and methods: We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Results: Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. Conclusion: ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research.

Original language	English
Pages (from-to)	117-126
Number of pages	10
Journal	European Journal of Cancer
Volume	137
DOIs	https://doi.org/10.1016/j.ejca.2020.06.030
State	Published - Sep 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd

Funding

All authors report being a Principal/sub-Investigator of Clinical Trials for Abbvie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro and Xencor; report receiving research grants from Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche and Sanofi and report receiving non-financial support (drug supplied) from Astrazeneca, Bayer, BMS, Boringher Ingelheim, Medimmune, Merck, NH TherAGuiX, Pfizer and Roche. C.M. reports receiving honoraria from Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi and Orion. S.C. reports receiving honoraria from AstraZeneca, BMS, Janssen, MSD, Novartis and Roche. A. H. has received honoraria from Amgen, Spectrum Pharmaceuticals, Lilly. J.C.S. reports receiving consultancy fees from AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen and Takeda over the past 3 years; reports serving as a full-time employee for AstraZeneca between September 2017–December 2019 and reports being a shareholder of Gritstone. A.M. reports receiving honoraria from GSK, AstraZeneca, Oncovir, Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Bayer, Novartis, BMS, Symphogen, Genmab, Amgen, Biothera, Nektar, Pfizer, Seattle Genetics, Flexus Bio, Roche/Genentech, OSE immunotherapeutics, Transgene, Gritstone, Merck (MSD), Cerenis, Innate pharma, Protagen, Partner Therapeutics and Servier. S.P.V. reports receiving honoraria from Merck KGaA and AstraZeneca. V. B. reports receiving honoraria from Bayer, Merck Serono, MSD, Roche, Sanofi and Ipsen. D.M. reports receiving honoraria from Amgen, Bayer, Merck Serono, MSD, Roche, Sanofi, HalioDx and Servier. All authors report being a Principal/sub-Investigator of Clinical Trials for Abbvie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro and Xencor; report receiving research grants from Astrazeneca , BMS , Boehringer Ingelheim , Janssen Cilag , Merck , Novartis , Pfizer , Roche and Sanofi and report receiving n on-financial support (drug supplied) from Astrazeneca, Bayer, BMS, Boringher Ingelheim, Medimmune, Merck, NH TherAGuiX, Pfizer and Roche. C.M. reports receiving honoraria from Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi and Orion. S.C. reports receiving honoraria from AstraZeneca, BMS, Janssen, MSD, Novartis and Roche. A. H. has received honoraria from Amgen, Spectrum Pharmaceuticals, Lilly. J.C.S. reports receiving consultancy fees from AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen and Takeda over the past 3 years; reports serving as a full-time employee for AstraZeneca between September 2017–December 2019 and reports being a shareholder of Gritstone. A.M. reports receiving honoraria from GSK, AstraZeneca, Oncovir, Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Bayer, Novartis, BMS, Symphogen, Genmab, Amgen, Biothera, Nektar, Pfizer, Seattle Genetics, Flexus Bio, Roche/Genentech, OSE immunotherapeutics, Transgene, Gritstone, Merck (MSD), Cerenis, Innate pharma, Protagen, Partner Therapeutics and Servier. S.P.V. reports receiving honoraria from Merck KGaA and AstraZeneca. V. B. reports receiving honoraria from Bayer, Merck Serono, MSD, Roche, Sanofi and Ipsen. D.M. reports receiving honoraria from Amgen, Bayer, Merck Serono, MSD, Roche, Sanofi, HalioDx and Servier.

Funders	Funder number
Basilea Pharmaceutica International Ltd
Cerenis
Cullinan-Apollo
HalioDx and Servier
Innate Pharma
Kyowa Kirin Pharma
Lytix pharma
Menarini Ricerche
Merck Sharp & Dohme Chibret
Merrimack Pharmaceuticals
Amgen
Bristol-Myers Squibb
Pfizer
Astellas Pharma US
AstraZeneca
Bayer
Genentech
GlaxoSmithKline
Novartis
Roche
Sanofi
Spectrum Pharmaceuticals
Boehringer Ingelheim
Janssen Pharmaceuticals
Merck KGaA
Clovis Oncology
Agios Pharmaceuticals
Boston Pharmaceuticals
Daiichi-Sankyo
Servier
Ipsen

Keywords

Chemotherapy after immunotherapy
Immunotherapy
Metastatic colorectal cancer
Microsatellite stable

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ejca.2020.06.030

Cite this

Martin-Romano, P., Ammari, S., El-Dakdoukti, Y., Baldini, C., Varga, A., Vuagnat, P., Angevin, E., Bahleda, R., Gazzah, A., Champiat, S., Michot, J. M., Postel-Vinay, S., Marabelle, A., Soria, J. C., Boige, V., Malka, D., Ducreux, M., Massard, C., & Hollebecque, A. (2020). Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer. European Journal of Cancer, 137, 117-126. https://doi.org/10.1016/j.ejca.2020.06.030

@article{61588e6ac6c1403bbb85d4b84e758fab,

title = "Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer",

abstract = "Background: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. Material and methods: We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Results: Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. Conclusion: ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research.",

keywords = "Chemotherapy after immunotherapy, Immunotherapy, Metastatic colorectal cancer, Microsatellite stable",

author = "Patricia Martin-Romano and Samy Ammari and Yolla El-Dakdoukti and Capucine Baldini and Andreea Varga and Perrine Vuagnat and Eric Angevin and Rastislav Bahleda and Anas Gazzah and Stephane Champiat and Michot, {Jean M.} and Sophie Postel-Vinay and Aurelien Marabelle and Soria, {Jean C.} and Valerie Boige and David Malka and Michel Ducreux and Christophe Massard and Antoine Hollebecque",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

month = sep,

doi = "10.1016/j.ejca.2020.06.030",

language = "אנגלית",

volume = "137",

pages = "117--126",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

}

Martin-Romano, P, Ammari, S, El-Dakdoukti, Y, Baldini, C, Varga, A, Vuagnat, P, Angevin, E, Bahleda, R, Gazzah, A, Champiat, S, Michot, JM, Postel-Vinay, S, Marabelle, A, Soria, JC, Boige, V, Malka, D, Ducreux, M, Massard, C & Hollebecque, A 2020, 'Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer', European Journal of Cancer, vol. 137, pp. 117-126. https://doi.org/10.1016/j.ejca.2020.06.030

TY - JOUR

T1 - Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer

AU - Martin-Romano, Patricia

AU - Ammari, Samy

AU - El-Dakdoukti, Yolla

AU - Baldini, Capucine

AU - Varga, Andreea

AU - Vuagnat, Perrine

AU - Angevin, Eric

AU - Bahleda, Rastislav

AU - Gazzah, Anas

AU - Champiat, Stephane

AU - Michot, Jean M.

AU - Postel-Vinay, Sophie

AU - Marabelle, Aurelien

AU - Soria, Jean C.

AU - Boige, Valerie

AU - Malka, David

AU - Ducreux, Michel

AU - Massard, Christophe

AU - Hollebecque, Antoine

PY - 2020/9

Y1 - 2020/9

N2 - Background: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. Material and methods: We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Results: Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. Conclusion: ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research.

AB - Background: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. Material and methods: We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Results: Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. Conclusion: ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research.

KW - Chemotherapy after immunotherapy

KW - Immunotherapy

KW - Metastatic colorectal cancer

KW - Microsatellite stable

UR - http://www.scopus.com/inward/record.url?scp=85088868392&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2020.06.030

DO - 10.1016/j.ejca.2020.06.030

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 32755794

AN - SCOPUS:85088868392

SN - 0959-8049

VL - 137

SP - 117

EP - 126

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Chemotherapy beyond immune checkpoint inhibitors in patients with metastatic colorectal cancer

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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