540P - Early treatment discontinuation (ETD) in dMMR/MSI-H metastastic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICIs)

Background

Although rare, late toxicities from immunotherapy can be serious. Most pivotal randomized trials have recommended a treatment duration of 2 years without a compelling rational. A shorter treatment duration has the potential to improve patients' quality of life while reducing toxicities and costs. Here we examine whether stopping treatment before 13 months (early treatment discontinuation [ETD]) in patients (pts) without disease progression (PD) can lead to long-term disease control.

Methods

To assess whether ETD is associated with similar outcomes compared to longer treatment duration (LTD), we selected, from an international cohort of dMMR/MSI-H mCRC pts treated with ICIs, pts who stopped treatment for a reason other than PD within 395 days (ETD group) and compared them to those who continued >395 days (LTD group).

Results

Of 976 pts, 137 and 394 were allocated to the ETD and LTD groups, respectively. In the ETD group, treatment was discontinued due to toxicity (n=56), objective response (n=43), surgery (n=28), pt decision (n=2) or other reasons (n=8). Baseline characteristics were well balanced between the two groups, 22% in both groups received combined anti-PD(L)1 + anti-CTLA4; all others received anti-PD(L)1 monotherapy. ORR to ICIs was 81% in both groups. Median duration of treatment was 7 months in the ETD group and 24 months in the LTD group. After a median follow-up of 44 months (IQR: 29.82-67.33), similar PFS and OS rates from the start of ICIs were observed in ETD and LTD pts (36 months -PFS rates: 79% vs 79%; -OS rates: 91% vs 89%, both NS). In the ETD group, 30 pts (22%) had a PFS event and 8 restarted ICI. The median time to ICI re-introduction was 14 months (IQR: 8.38-16.90). In these pts, disease control rate was 67% and 12 months-PFS and OS rates were 63% (95%CI: 37-100) and 88% (95%CI: 67-100), respectively.

Conclusions

In our international series of dMMR/MSI-H mCRCs, ETD of ICIs in the absence of PD was not detrimental in terms of PFS and OS compared with continuing treatment beyond one year. Randomized clinical trials to compare short and longer treatment duration are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

AGEO.

Funding

Has not received any funding.

Disclosure

J. Taieb: Financial Interests, Personal, Advisory Board: MSD, astellas, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, sanofi, rottapharm, takeda, takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: astelllas; Financial Interests, Personal, Other, steering committe of clinical trial: novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD); Non-Financial Interests, Other, steering committee of clinical trials: pfizer, servier. E.L. Alouani: Financial Interests, Personal, Advisory Board: MERCK, Servier. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, merck serono, lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, Astellas, GSK, Takeda, Bayer, Rottapharm; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, GSK, Roche, Servier, Amgen, Bristol-Myers Squibb, Incyte, Lilly, Merck Serono, MSD, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol -Myers Squibb; Non-Financial Interests, Member of Board of Directors, Italian No-Profit Oncology Research Foundation supporting academic Clinical trials: GONO Foundation. F.A. Sinicrope: Financial Interests, Personal, Advisory Board: Roche, Guardant Health, Eisai; Financial Interests, Institutional, Royalties: Roche/Ventana Medical Systems; Non-Financial Interests, Principal Investigator, Clinical trials: Alliance for Clinical Trials in Oncology; Non-Financial Interests, Advisory Role, Colon Cancer Task Force: National Cancer Institute. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, EISAI, BMS; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Theraeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345 ; M21-404: Abbvie; Non-Financial Interests, Principal Investigator, CO42216 ; WP42627 ; CO40939 ; GO44479 ; GO42216: Roche; Non-Financial Interests, Principal Investigator, MCLA-158 ; MCLA-128: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002 ; SGNB6A: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH ; Loxo-RAS: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim; Non-Financial Interests, Principal Investigator, CA120-1001: BMS. T. Mazard: Financial Interests, Personal, Advisory Board: Pierre Fabre, Servier; Financial Interests, Personal, Invited Speaker: Servier, Sanofi, Pierre Fabre; Financial Interests, Personal, Other, Development of clinical cases for regional meetings: MERCK SERONO; Financial Interests, Personal, Writing Engagement: Galapagos; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Advisory Role, development of guidelines about molecular testing in colorectal cancers: INCA; Other, travel grant: Pierre Fabre, Merck Serono, Sanofi, MSD. S. Pernot: Financial Interests, Personal, Invited Speaker: bayer, amgen, Pierre Fabre, AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, BMS, Servier, Merck, Takeda. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda, Boehringer Ingelheim, Cure Teq AG, Repare Therapeutics Inc., RIN Institute Inc., Janssen; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer, BMS, Lilly, Medscape; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol-Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune, Abbvie Deutschland Gmbh & Co KG, Bayer Pharma AG, Bioncotech Therapeutics, S.L., Biontech Rna Pharmacuticals GMBH, Biontech Small Molecules GMBH, Boehringer Ingelheim de España S.A., Daiichi Sankyo, Inc, Gercor, Hutchinson Medipharma Limited, Iovance Biotherapeutics, Inc., Janssen Research & Development, Menarini Ricerche SPA, Merck, Sharp & Dohme De España S.A., Nouscom SRL., Pledpharma AB, Redx Pharma PLC, Scandion Oncology, Seattle Genetics Inc., Sotio A.S., Wntresearch AB; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023-2024 term: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Other, Travel, Accommodations, Expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol-Myers Squibb. M.J. Overman: Financial Interests, Personal, Advisory Board: Roche, BMS, Medimmune, Merck, Amgen, Takeda, Janssen, PFizer, Array, Gritstone, Nousome, Atreca, Bayer, Summit, Agenus, Regeneron, Astellas; Financial Interests, Institutional, Coordinating PI: roche, lilly, merck, bms, phanes, nouscom. L. Salvatore: Financial Interests, Personal, Advisory Board: Takeda, Pierre-Fabre, GSK, servier, Bayer, MSD, Amgen, Merck, Leopharma; Financial Interests, Personal, Invited Speaker: Takeda, Pierre Fabre, Servier, Bayer, MSD, Incyte, AstraZeneca, Amgen, Merck. R. Guimbaud: Financial Interests, Personal, Advisory Board: ADACAP, BMS; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Bayer, Esteve, Pierre Fabre, Merck. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Institutional, Coordinating PI: Roche, Bayer, Servier, Merck; Financial Interests, Institutional, Local PI: seagen, Hutchinson. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation francophone de cancerologie digestive. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck-Serono, MSD, Bayer, Astellas, Takeda, Ipsen, GSK, Johnson&Johnson, Rottapharm; Financial Interests, Personal, Invited Speaker: Amgen, Merck-Serono, BMS, Lilly, Servier, Bayer, Pierre-Fabre, AstraZeneca, Astellas, Daiichi Sankyo, Takeda; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus; Financial Interests, Institutional, Coordinating PI: Lilly, Amgen. All other authors have declared no conflicts of interest.