Discussion
diarrhea, soft-tissue sarcomas, sarcomas, proteinuria, anemia, rash, sarcoma, lung vein embolism, deaths, hypertension, TRAEs
HYPERCHOLESTEROLEMIA, PNEUMOTHORAX, INTERSTITIAL PNEUMONIA, SARCOMAS, DISEASE, EVENTS, ANEMIA, SARCOMA, HYPERTRIGLYCERIDEMIA, HYPOTHYROIDISM, HYPERTENSION, PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
Patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma have limited treatment options after failure of chemotherapy. Although monotherapy with angiogenesis-targeted TKI or ICI has been developed, the outcomes are far from satisfactory. In this study, we adopted intensive immunotherapy-antiangiogenesis combination with MASCT-I, camrelizumab, and apatinib. This combination was generally safe with serious TRAEs in 15.8% of patients and no treatment-related deaths. Promising efficacy was indicated with 31.6% of patients achieving an objective response and 68.4% of patients having non-progressive disease. To our knowledge, this is the first reported trial of a combination with DC-based cellular immunotherapy, PD-1 blockade, and VEGF blockade in sarcoma.The most common TRAEs of this triple therapy included decreased neutrophil count, hypertriglyceridemia, proteinuria, hypothyroidism, hypercholesterolemia, decreased white blood cell count, anemia, increased blood bilirubin, decreased platelet count, diarrhea, hypertension, palmar-plantar erythrodysesthesia syndrome, increased aspartate aminotransferase, and rash. The safety profile was similar with individual components; no new safety signals were identified and no deaths were attributed to study treatment. Serious TRAEs were reported in 15.8% of patients, including interstitial pneumonia, lung vein embolism, pneumothorax, and infusion-related reaction; however, 3 of the 4 (75.0%) events resolved at cutoff date.In the schedule-I and schedule-II groups, all patients developed TRAEs, but patients in the schedule-II group showed a relatively higher incidence of grade 3 or 4 TRAEs than those in the schedule-I group (70.0% versus 44.4%), which could be explained, in part, by the longer exposure of all components of study treatment in the schedule-II group. Nevertheless, the schedule-II administration method was associated with better clinical outcomes compared with the schedule-I, with a DCR of 90.0% versus 44.4% and a median PFS of 7.7 versus 4.0 months. Besides, the schedule-II had the advantage of shorter course (7 versus 13 weeks for the first course). Three consecutive injections of multiple antigen-loaded DCs with a 7-day interval might be beneficial to rapidly activate the body’s immune responses. Hence, we recommended the schedule-II administration method for further investigations.In this study, patients with soft-tissue sarcomas achieved an ORR of 30.8% and a median PFS of 12.9 months, which were numerically superior to the historical data of angiogenesis-targeted TKIs including apatinib, pazopanib, and anlotinib (ORR, 15.8% or less; median PFS, 5.6 months or less), those of ICI pembrolizumab (18%; 18 weeks), and those of TKI axitinib plus ICI pembrolizumab (25.0%; 4.7 months) [The limitations of this study are typical of an early-phase clinical trial, such as small sample size, lack of randomization, and single-center setting. MASCT-I plus camrelizumab and apatinib showed clinical meaningful preliminary efficacy in advanced sarcomas, regardless of subtypes. However, due to high heterogeneity in subtypes and limited numbers of patients for each subtype, further investigations are needed.