1127P - Efficacy of immune checkpoint inhibitors (ICIs) in advanced mucosal melanoma (MM): A systematic review and meta-analysis

Background

Unresectable or metastatic MM has been associated with worse survival and inferior treatment responses than cutaneous melanoma. ICIs are commonly used to treat advanced MM; however, robust conclusions on their efficacy are limited by small studies with heterogeneous patient populations.

Methods

A systematic review and meta-analysis was conducted to benchmark the efficacy of ICIs in advanced MM. PubMed, Medline, Embase, Web of Science and CENTRAL were searched in April 2023 using a combination of ICI and MM search terms, restricted to primary studies with at least 5 patients. Logit-transformed objective response rates (ORR) and adverse event (AE) rates were pooled using a random effects model and the inverse variance methods. Progression-free survival (PFS) and overall survival (OS) Kaplan-Meier curves were digitalised and used to construct summary plots, from which median estimates were derived. Results are reported with 95% confidence intervals.

Results

28 studies reporting on ICIs in advanced MM were identified (n=2008). 37 treatment types were reported – 10 anti-CTLA4 (n=212), 21 anti-PD1 (n=1428) and 6 anti-CTLA4 plus anti-PD1 (n=368). 62% of patients were treatment-naïve. Pooled ORR was 10% (7-13) for anti-CTLA4, 23% (22-28) for anti-PD1 and 31% (28-35) for anti-CTLA4 plus anti-PD1 (P<0.001). Median PFS was 3.5 months (2.7-4.7) for anti-CTLA4, 4.0 months (2.9-5.2) for anti-PD1 and 4.7 months (3.6-6.6) for anti-CTLA4 plus anti-PD1 (P<0.001). Median OS was 7.2 months (5.7-10.6) for anti-CTLA, 14.4 months (10.8-17.5) for anti-PD1 and 19.4 (13.8-21.2) for anti-CTLA4 plus anti-PD1 (P<0.001). Grade 3 and higher AEs occurred in 36% (1-95) of patients for anti-CTLA4, 14% (11-18) for anti-PD1 and 50% (33-58) for anti-CTLA4 plus anti-PD1.

Conclusions

ICIs are associated with modest activity in patients with advanced MM. Although efficacy is slightly greater with combined anti-CTLA4/anti-PD1 compared to anti-PD1 alone, this was associated with a significantly high risk of grade 3+ AEs. Recommendations for combination ICI therapy should involve a risk-benefit analysis for individual patients. Research to identify predictive molecular biomarkers for ICI efficacy may help with treatment selection for advanced MM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis; Financial Interests, Personal, Other, Consulting and/or advisory role: Merck Sharp & Dohme (MSD); Financial Interests, Personal, Other, Consulting and/or advisory role: Bristol Myers Squibb (BMS); Financial Interests, Personal, Other, Consulting and/or advisory role: Roche; Financial Interests, Personal, Other, Consulting and/or advisory role: Amgen; Financial Interests, Personal, Other, Consulting and/or advisory role: Takeda; Financial Interests, Personal, Other, Consulting and/or advisory role: Pierre Fabre; Financial Interests, Personal, Other, Consulting and/or advisory role: Sun Pharma; Financial Interests, Personal, Other, Consulting and/or advisory role: Sanofi; Financial Interests, Personal, Other, Consulting and/or advisory role: CatalYm; Financial Interests, Personal, Other, Consulting and/or advisory role: Second Genome; Financial Interests, Personal, Other, Consulting and/or advisory role: Regeneron; Financial Interests, Personal, Other, Consulting and/or advisory role: Alligator; Financial Interests, Personal, Other, Consulting and/or advisory role: MaviVAX SA; Financial Interests, Personal, Other, Consulting and/or advisory role: Simcere; Financial Interests, Personal, Other, Consulting and/or advisory role: touchIME; Financial Interests, Personal, Other, Consulting and/or advisory role: T3 Pharma; Financial Interests, Personal, Other, Consulting and/or advisory role: Pfizer. All other authors have declared no conflicts of interest.