Toripalimab plus gemcitabine and cisplatin as novel first-line treatment for recurrent or metastatic nasopharyngeal carcinoma
To date, treatment options for recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) have been limited. At ASCO 2021, results of the phase III JUPITER-02 study indicate that the combination of toripalimab with gemcitabine and cisplatin is associated with a significantly better progression-free survival than chemotherapy alone in the first-line treatment of patients with R/M NPC.
Nasopharyngeal carcinoma (NPC) is an endemic malignancy is Southern China and Southeast Asia. To date, gemcitabine-cisplatin (GP) chemotherapy has been the current standard first-line therapy for these patients worldwide. Toripalimab, a humanised IgG4K monoclonal antibody specific for human PD-1, provided durable responses in patients with R/M NPC as monotherapy in second-line and beyond (POLARIS-02 study). Building on this result, JUPITER-02, the first global, double-blind, placebo-controlled phase III study, evaluates GP chemotherapy in combination with toripalimab or placebo as first-line treatment in patients with R/M NPC.
JUPITER-02 study design
From November 2018 to October 2019, a total of 408 patients with primary metastatic NPC or recurrent NPC after curative-intent surgery from 35 sites in mainland China, Taiwan and Singapore were screened. In total, 289 patients were randomly assigned (1:1) to the toripalimab or placebo arm. In the toripalimab arm, patients received 240 mg toripalimab plus gemcitabine (1,000 mg/m2) and cisplatin (80 mg/m2) once every three weeks (Q3W) for up to six cycles. In the other arm, patients were treated with placebo + GP Q3W up to six cycles. After these six cycles, patients received toripalimab or placebo monotherapy maintenance Q3W until disease progression, intolerable toxicity, or completion of two years of treatment. The primary endpoint of the study was progression-free survival (PFS) by a blinded independent review committee (BIRC) per RECIST v1.1 criteria.
Superior progression-free and overall survival with toripalimab-based therapy
Baseline patient and disease characteristics were generally well balanced between both treatment arms, with approximately 75% of patients having a PD-L1 positive tumour biopsies A significant improvement in PFS was reported for patients in the toripalimab arm compared to patients who only received chemotherapy (median PFS 11.7 vs. 8.0 months, HR[95%CI]: 0.52[0.36-0.74], p= 0.0003). At one year, this translated into a PFS rate of 49.4% and 27.9% for the toripalimab and placebo arms, respectively. An improvement in PFS was observed across all relevant subgroups, irrespective of the PD-L1 expression level. The objective response rates (ORR) were 77.4% vs. 66.4% (p= 0.0335), in favour of the toripalimab combination, with complete responses obtained in 19.2% and 11.2% of patients, respectively. The median duration of response (DoR) was 10.0 vs. 5.7 months (HR [95%CI]: 0.50[0.33-0.78], p= 0.0014). Although median overall survival (OS) was not mature in either arm, a 40% reduction in the risk of death was observed in the toripalimab arm over the placebo arm (HR[95%CI]: 0.603[0.364-0.997], p= 0.0462). Similar incidences of adverse events (AEs) related to study drugs (95.2% vs. 97.2%), infusion reactions (4.1% vs. 4.2%) and fatal AEs (2.7% vs. 2.8%) were reported in the toripalimab and placebo arms, respectively. As expected, immune-related AEs (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. The most common adverse events of grade ≥3 in the toripalimab arm were leukopenia (61.6%), anaemia (47.3%), neutropenia (57.3%) and thrombocytopenia (32.9%), mostly related to the chemotherapy regimen.
JUPITER-02 is the first international phase III trial to prove that the addition of toripalimab to gemcitabine and cisplatin as a first-line treatment for recurrent or metastatic NPC patients provides a superior PFS, OS, ORR and DoR compared to chemotherapy alone. In addition, the combination was found to be safe, without any new safety signals.
Xu RH, Mai HQ, Chen QY, et al. JUPITER-02: randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). Presented at ASCO 2021; abstract LBA2.