Uveal melanoma is a distinct subtype of melanoma. Several previously reported studies showed that anti-PD-1 or PD-L1 antibodies, which are efficacious for cutaneous melanoma with tolerable toxicities, had only limited activities on metastatic uveal melanoma. However, since most of the patients in those studies were previously treated with ipilimumab, the efficacy of anti-PD-1 antibody when it is used prior to ipilimumab for metastatic uveal melanoma is less clear.
To evaluate the efficacy of nivolumab for Asian patients with metastatic uveal melanoma previously untreated with ipilimumab, we carried out a retrospective study using a database of National Cancer Center Hospital, Tokyo, Japan, in which nivolumab was approved one year earlier than ipilimumab. As clinical efficacy outcomes, best overall response which was evaluated by RECIST 1.1, progression-free survival (PFS), and overall survival (OS) were determined.
We identified 14 patients with metastatic uveal melanoma who received nivolumab at a dosage of 3mg/kg every 2 weeks or 2mg/kg every 3 weeks. Median age was 59.5 (range, 42 - 74), and 11 patients were male. Performance status was 0 in 9 patients and 1 in 5 patients. All the patients had liver metastases and 9 patients had additional extrahepatic metastases. At baseline, serum lactate dehydrogenase (LDH) was elevated in 8 patients. Although 8 patients had previous treatment history of transarterial chemoembolization (TACE), none of the 14 patients had received any prior systemic therapies including ipilimumab. Of 12 evaluable patients, objective tumor response was observed in 1 patient for an overall response rate of 8.3%, and stable disease was observed in 5 patients. The median PFS was 10 weeks (range, 4 – 94 weeks), and the median OS was 58 weeks (range, 5 – 105 weeks).
Even though nivolumab is used prior to ipilimumab, metastatic uveal melanoma seems to be still refractory to nivolumab monotherapy. However, since one patient in our cohort achieved objective response, treatment strategies in combination with anti-PD1 antibody should be further investigated.
National Cancer Center Hospital
Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED, 17ck0106352h0001) and the National Cancer Center Research and Development Fund (29-A-3).
K. Namikawa: Honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Novartis Pharmaceutical, Toray industries, and Chugai Pharmaceutical, outside the submitted work. N. Motoi: Honoraria from Agilent Technologies, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Leica Microsystems, MSD, Novartis Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, and SRL, outside the submitted work. N. Yamazaki: Research grant and honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Novartis Pharma, and MSD.
All other authors have declared no conflicts of interest.