71P - Discontinuation of immune checkpoint inhibitors for reasons other than disease progression and the impact on relapse and survival of advanced melanoma patients: A systematic review and meta-analysis

Background

Despite durable responses achieved with Immune Checkpoint Inhibitors (ICIs), data about optimal duration of treatment, especially in the context of adverse events, remain scarce.

Methods

A systematic literature search was conducted in three electronic databases until July 2024. Studies referring to melanoma patients who ceased ICIs electively (i.e. due to complete response (CR), protocol completion or patient/physician’s wish) or due to treatment-limiting toxicities (TLTs) were selected. Relapse rates (RRs) post cessation, time to PD, rechallenge and disease control rate (DCR) after 2^nd course were the main outcomes. Random-effects models were preferred, and subgroup and sensitivity analyses were conducted to investigate possible sources of heterogeneity.

Results

38 and 35 studies were included in qualitative and quantitative synthesis, respectively. From 2542 patients who discontinued treatment with ICIs, 495 experienced progression (n=34, RR 20.9%,95%CI 17.1–24.7%, I²85%); higher rates were detected in patients with TLTs compared to elective disc. Mean time to PD was 14.26 months (n=18, mean time 14.26,95%CI 11.54–16.98,I²93%) and was numerically longer in patients ceased for CR compared to patients with TLTs. Treatment duration before cessation was not associated with risk and time to relapse, while mucosal melanomas and non-CR as BOR during treatment led to increased risk for relapse and shorter time to PD compared to other histologic subtypes or CR. Rechallenge with ICI resulted in 57.3% DCR and 28.6% pooled CR rates (n=22, CR rate 28.6%, 95%CI 17.1–40.2, I²68%). Subgroup analysis (type of ICI) and sensitivity analyses did not alter the results significantly. Table: 71P

Conclusions

Discontinuation of ICIs in patients without progression is possible. Outcomes to rechallenge with ICIs may differ depending on the reason for discontinuation, but remains a considerable option.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

U. Leiter-Stoppke: Financial Interests, Personal, Advisory Board, and speaker's honoraria: Sun Pharma, Regeneron, Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre, Novartis, Almirall Hermal; Financial Interests, Institutional, Research Grant: MSD. L. Flatz: Financial Interests, Personal, Full or part-time Employment, Section Head of Dermato-oncology: University Hospital of Tübingen; Financial Interests, Personal, Stocks/Shares, Founder: Hookipa Pharma, Humion AG; Financial Interests, Personal, Ownership Interest, Founder: Abtherix GmbH, Schmelzberg GmbH; Financial Interests, Personal, Royalties, IP owner together with University of Zurich: Hookipa Pharma; Non-Financial Interests, Personal, Advisory Role: Philogen. T.M.S. Amaral: Financial Interests, Personal, Writing Engagement: CeCaVa, Medtrix; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pierre Fabre, Neracare; Financial Interests, Personal, Advisory Board: Delcath, Philogen; Financial Interests, Institutional, Funding: Novartis, Neracare, Sanofi, Skyline-Dx, Pascoe, MNI - Naturwissenschaftliches und Medizinisches Institut; Financial Interests, Institutional, Research Grant: Novartis, iFIT; Financial Interests, Institutional, Local PI: IO Biotech, MSD, University Hospital, Essen, Roche, BMS, BioNTech, Philogen, Pfizer, Immunocore, HUYA Bioscience, AstraZeneca, Agenus Inc., Regeneron; Financial Interests, Institutional, Coordinating PI: Unicancer; Non-Financial Interests, Personal, Member: Portuguese Society for Medical Oncology, ASCO; Other, Personal, Other, Clinical expert in the area of medical oncology: INFARMED - PT. All other authors have declared no conflicts of interest.