Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The addition of toripalimab to first-line standard of care gemcitabine plus cisplatin (GP) chemotherapy significantly improves the outcomes of patients with recurrent or metastatic nasopharyngeal carcinoma after curative intent therapy, suggests research presented at the 2021 ASCO Annual Meeting.
The PD-1 inhibitor was previously approved in China as a third-line treatment for this indication on the basis of the POLARIS-02 findings, explained presenting author Rui-hua Xu, from Sun Yat-Sen University Cancer Center in Guangzhou, China.
He believes that the latest phase III results of the JUPITER-02 trial, conducted in China, Taiwan and Singapore, indicate that “toripalimab in combination with gemcitabine and cisplatin may represent a new standard of care for first-line treatment for recurrent or metastatic [nasopharyngeal carcinoma].”
The primary endpoint of blinded independent review committee-assessed progression-free survival (PFS) was a median 11.7 months for the 146 patients randomly assigned to receive up to six cycles of toripalimab 240 mg every 3 weeks plus gemcitabine 1000 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1 of each cycle, with toripalimab maintenance continuing on the same dosage for up to 2 years.
This compared with a median 8.0 months for the 143 patients instead given placebo with chemotherapy, giving a significant stratified hazard ratio (HR) of 0.52 for disease progression or death in favour of the PD-1 inhibitor’s use.
The 1-year PFS rates in the combination and GP-only arms were 49.4% and 27.9%, respectively. And subgroup analysis significantly favoured use of toripalimab regardless of sex, ECOG performance status, recurrent or metastatic disease status, EBV copy number and PD-L1 expression. However, the PFS benefit only reached statistical significance in patients aged less than 50 years and not older participants.
Nine months after PFS interim analysis was performed, median overall survival (OS) was unreached in both treatment arms but the stratified HR for death was a significant 0.60 in favour of toripalimab plus GP versus GP alone.
The corresponding 1-year OS rates were 91.6% and 87.1%, with 2-year rates of 77.8% and 63.3%.
The objective response rate was 77.4% with toripalimab plus GP, with 19.2% of patients achieving a complete and 58.2% a partial response, and 10.3% stable disease, with a median duration of response of 10.0 months. The corresponding values for GP only were 66.4%, 11.2%, 55.2%, 13.3% and 5.7 months, respectively.
The presenter said there were “no new safety signals” identified for the combination treatment. Grade 3 and more severe treatment-related adverse events (AEs) occurred in 80.8% of patients given toripalimab plus GP versus 83.2% of those given placebo plus GP, with immune-related AEs of this severity reported in 7.5% and 0.7%, respectively.
The most common grade 3 and more severe treatment-emergent AEs with the toripalimab combination were haematological and mostly attributed to the GP regimen, the presenter remarked, most commonly leukopenia (61.6 vs 58.0% with GP only), neutropenia (57.5 vs 63.6%), anaemia (47.3 vs 39.9%) and thrombocytopenia (32.9 vs 28.7%).
Rui-hua Xu concluded that a second interim OS analysis is now planned, and this will be followed by the prespecified final PFS and OS analyses for the JUPITER-02 trial.
Session discussant Anthony Chan, from the Hong Kong Cancer Institute, noted that the PFS curves in the JUPITER-02 study appear to separate at the point where systemic therapy ends and maintenance toripalimab or placebo is initiated, with a similar pattern occurring in the immature OS curves.
“Whether this improvement of toripalimab over placebo can be achieved by using maintenance systemic chemotherapy is obviously an open question”, he remarked.
The discussant concluded that first-line cisplatin plus gemcitabine “remain the standard of care” for this patient population until the OS benefits can be demonstrated as “practice changing” by an adequately powered analysis.
He added that the “role of maintenance systemic therapy remains to be defined” but that there is “tremendous potential” for combination immunotherapy strategies and biomarker-directed treatment sequencing in nasopharyngeal carcinoma, with current ongoing studies assessing PD-1 inhibitors in combination with immunotherapy agents, signalling inhibitors and bispecific or antibody–drug conjugates.
Reference
Xu R-h, Mai H-Q, Chen Q-Y, 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). J Clin Oncol 2021;39(suppl 15; abstr LBA2). DOI: 10.1200/JCO.2021.39.15_suppl.LBA2
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