Toripalimab Enhances Chemotherapy Efficacy in Advanced Nasopharyngeal Cancer
Nasopharyngeal cancer (NPC) is a relatively rare malignancy in Western countries, but it is endemic in Southern China and Southeast Asia. Due to an anatomically ‘’silent’’ location and non-specific symptoms, most NPC patients are diagnosed at an advanced stage. The standard first-line treatment for these patients is platinum-based chemotherapy, such as gemcitabine and cisplatin. Although responses to chemotherapy are high, they are rather short-lived and there is a high unmet need for better treatment strategies. Toripalimab is a recombinant humanized anti-PD-1 monoclonal antibody that was recently approved in China as third-line therapy for recurrent or metastatic (R/M) NPC based on the durable responses and survival benefit demonstrated in the phase II POLARIS-02 trial. The US Food and Drug Administration has granted toripalimab Breakthrough Therapy designation for the treatment of NPC, and in March 2021 submission of Biologic License Application (BLA) was initiated for R/M NPC.
At this year’s ASCO plenary session, results from an interim analysis of the phase III JUPITER-02 trial, which evaluated toripalimab in combination with chemotherapy as first-line treatment for patients with R/M NPC, were presented by Dr Rui-Hua Xu (Sun Yat-sen University Cancer Center, Guangzhou, China). In this double-blind, placebo-controlled trial, treatment-naïve patients from mainland China, Taiwan, and Singapore were randomized to receive either toripalimab (240 mg; n=146) or placebo (n=143) in combination with gemcitabine and cisplatin for up to 6 cycles, followed by maintenance monotherapy with toripalimab or placebo until disease progression or intolerable toxicity. A significant improvement was seen in progression-free survival (PFS) by the blinded independent review committee (BIRC) in the toripalimab arm compared with placebo (hazard ratio [HR], 0.52; P=0.0003). The PFS rate at 1 year was 49.4% versus 27.9%, and median PFS was 11.7 versus 8.0 months, respectively. The improvement in PFS was consistent across all key subgroups, notably in both PD-L1-positive and PD-L1-negative patients. The overall survival (OS) data were immature at the interim analysis; however, the OS update at 9 months after this analysis showed a significant 40% reduction in the risk of death with toripalimab versus placebo (HR, 0.60; P=0.0462). The objective response rate (ORR) was higher in the toripalimab arm compared with placebo (77.4% versus 66.4%), and the median duration of response (DoR) was nearly doubled (10.0 versus 5.7 months). Importantly, the combination of toripalimab plus chemotherapy had a comparable safety profile to chemotherapy alone, including a similar incidence of grade ≥3 adverse events (AEs), discontinuation rates, infusion reactions, and deaths. However, immune-related AEs were more frequent with toripalimab (39.7% versus 18.9%) with grade ≥3 immune-related AEs occurring in 7.5% of patients versus 0.7% with placebo.
Dr Xu concluded that the results from JUPITER-02 support the use of first-line toripalimab in combination with gemcitabine and cisplatin chemotherapy as the new standard of care for patients with advanced NPC. The abstract discussant, Dr Anthony Chan (Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong) highlighted that the PFS benefit seen with first-line toripalimab plus chemotherapy in R/M NPC is highly encouraging and the data indicate that maintenance toripalimab is beneficial versus placebo. He noted that the results may be practice changing if a suitably powered study can confirm the OS benefit. Dr Chan also pointed out the potential for dynamic biomarkers, such as EBV DNA or circulating tumor DNA, to guide optimal treatment sequencing.
Xu, RH, et al. ASCO 2021; Abstract LBA2.