Abstract 1046P
Background
Anti-PD-1 antibody monotherapy (PD1) leads to favorable responses in advanced cutaneous melanoma (CM) among Caucasian populations; however, recent studies have indicated limited efficacy in mucosal melanoma (MM) than in CM. Thus, advanced MM patients (pts) are candidates for anti-PD-1 plus anti-CTLA-4 combination therapy (PD1+CTLA4). Meanwhile, data on the efficacy of immunotherapy in MM are limited. We aimed to compare the efficacies of first-line PD1 and PD1+CTLA4 in Japanese advanced MM pts in the real-world setting.
Methods
Advanced MM pts who received PD1 or PD1+CTLA4 were included from 24 Japanese institutions. Clinical responses were assessed using the RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 5.0.
Results
Altogether, 329 pts with advanced MM (head and neck 184; urogenital organs 76; gastrointestinal tract, 69) were included in the study. PD1 and PD1+CTLA4 were used in 263 and 66 pts, respectively. Baseline characteristics such as ECOG performance status, TNM stage, LDH level, and the number of metastatic organ sites were comparable between the PD1 and PD1+CTLA4 groups, except for age (median age 71 vs. 65; P < 0.001). No significant differences in objective response rate were observed between the PD1 and PD1+CTLA4 groups (26% vs. 29%; P = 0.26) or PFS and OS (median PFS 5.9 months vs. 6.8 months; P = 0.55, median OS 20.4 months vs. 20.1 months; P = 0.54). Multivariate survival analysis using Cox proportional hazards model revealed that PD1+CTLA4 did not prolong PFS and OS (PFS: hazard ratio (HR) 0.83, 95% confidential interval (CI) 0.58–1.19, P = 0.30; OS: HR 0.89, 95% CI 0.57–1.38, P = 0.59), although ECOG performance status 0, normal LDH level, and a small number of metastatic sites impacted PFS and OS. Due to immune-related adverse events, the treatment cessation rate was higher in the PD1+CTLA4 group than in the PD1 group (55% vs. 17%).
Conclusions
First-line PD1+CTLA4 did not present better clinical efficacy than PD1 in Japanese MM pts, despite the higher rate of immune-related adverse events.
Clinical trial identification
Editorial acknowledgement
English language editing was provided by Editage.
Legal entity responsible for the study
The authors.
Funding
National Cancer Center Research and Development Fund.
Disclosure
Y. Nakamura: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Maruho; Financial Interests, Personal, Invited Speaker: Taisho Toyama Pharma; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Tanabe Mitsubishi Pharma; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Novartis Pharma; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Institutional, Funding: Ono Pharmaceutical; Financial Interests, Institutional, Funding: Kaken Pharma; Financial Interests, Institutional, Funding: Torii; Financial Interests, Institutional, Funding: POLA Pharma. K. Namikawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Takara Bio; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis. S. Yoshikawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma. T. Maekawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme. O. Yamasaki: Financial Interests, Institutional, Funding: Ono Pharmaceutical. T. Isei: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Ono Pharmatheutical; Financial Interests, Personal, Advisory Board: Pfizer. S. Matsushita: Financial Interests, Personal, Advisory Board: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Kyowa Kirin. S. Fukushima: Financial Interests, Institutional, Funding: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Ono Pharmatheutical; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb. T. Takenouchi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme. H. Kato: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma. A. Otsuka: Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Institutional, Funding: Eisai. T. Inozume: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.