Combination of pembrolizumab (PEMBRO) plus temozolomide (TMZ) therapy in Chinese patients (pts) with advanced acral and mucosal melanoma.

Abstract

e21505 Background: Acral and mucosal melanoma are rare in Caucasians but have higher incidence in Asians and have poor prognosis. However, it has been reported that monotherapy seems to have limited efficacy in these population. Therefore, new treatments especially novel combination therapy are needed to further improve the outcome for these two subtypes. Here, we present the efficacy and safety of PEMBRO combined with TMZ in previously untreated pts with advanced acral and mucosal melanoma in China. Methods: The records of pts in Fudan University Shanghai Cancer Center with metastatic and unresectable acral and mucosal melanoma firstly treated with PEMBRO plus TMZ, PEMBRO alone or TMZ/DTIC based chemotherapy (CHEMO) were reviewed. Data regarding to best objective response rate (ORR), progression free survival (PFS) and toxicities were estimated. Response to treatment was assessed based on direct review of scan images and radiology reports according to the RECIST 1.1 criteria. Safety and tolerability were assessed per NCI-CTCAE v 4.0. Results: From May 2018 to February 2020, 49 pts were identified, including 28 (57.1%) with acral melanoma, 21 (42.9%) with mucosal melanoma. 32 (65.3%) pts had prior received adjuvant treatment, of which most (15, 30.6%) were interferon-α (IFN-α) or interleukin-2 (IL-2). Among these pts, PEMBRO alone was received by 18 (36.7%) pts with standard dosing of 2 mg/kg every 3 weeks. 20 (40.8%) pts received CHEMO at standard recommended dosing schedule, of which TMZ was given at 200 mg/m2 orally days 1–5, every 4 weeks. PEMBRO plus TMZ was given to 11 (22.4%) pts with the same dosing of each treatment alone. The ORR of PEMBRO plus TMZ (6/11, 54.5%) was significantly higher than PEMBRO alone (2/18, 11.1%; p = 0.011) or CHEMO(1/20, 5.0%; p = 0.002), however, the difference of ORR between PEMBRO alone and CHEMO was not statistically significant ( p = 0.485). The disease control rate of the three groups were 81.8%, 72.2% and 70.0% respectively (not significant). The median PFS of PEMBRO plus TMZ in the front-line therapy was 9.8 months (95% CI, 3.2 -16.4), as compared with 6.2 months (95% CI, 1.8 - 10.3) in PEMBRO alone and 4.2 months (95% CI, 2.8 - 5.6) in CHEMO ( p = 0.258). Grade 3 treatment-related adverse events (TRAEs) occurred in one acral melanoma patient (rash) in PEMBRO plus TMZ and two pts in CHEMO (one thrombocytopenia and one anemia, both were mucosal melanoma). No grade 3 TRAEs was reported in PEMBRO alone. There were no significant differences in grade 1/2 toxicity, with the common TRAEs including nausea, vomiting, fatigue, elevated transaminase and leukocytopenia. Conclusions: These results suggest that the combination of PEMBRO plus TMZ as first line therapy for advanced acral and mucosal melanoma could potentially be an effective strategy to enhance antitumor activity with a manageable toxicity profile. Need to be further evaluated in a large prospective study.