Virtual – A new immunotherapy molecule, toripalimab, could transform the treatment of nasopharyngeal cancer (CNP). This monoclonal antibody which blocks the PD-1 protein (programmed cell death protein 1) was developed in China where it was recently approved as a third-line treatment for CNP, among others. In the United States, the Food and Drug Administration (FDA) has granted it the status of an innovative treatment for recurrent or metastatic CNP, as well as an orphan drug status in the accelerated evaluation procedure for other types of tumor. .
New results show that when toripalimab is added to cisplatin and gemcitabine chemotherapy for the first-line treatment of relapsed CNP or metastatic CNP, there is a significant improvement in both progression-free survival and overall survival.
Participants were randomized: 146 patients received toripalimab and 143 received placebo in addition to chemotherapy with cisplatin and gemcitabine, which is now the standard treatment for CNP in relapsed or metastatic conditions.
The median progression-free survival (PFS) was 11.7 months with toripalimab versus 8 months with placebo, which is a significant improvement (hazard ratio, 0.52; 95% CI [0,36-0,74], P = 0.0003). The overall survival data were not mature at the time of analysis but they seemed in favor of toripalimab with 25 deaths, compared to 39 in the placebo group, which corresponds to a 40% reduction in the risk of mortality (P = 0.0462).
The results “encourage the use of toripalimab in combination with [la gemcitabine et le cisplatine] as a new first-line reference treatment for recurrent or metastatic CNP ”explained the principal investigator, le Dr Rui-Hua Xu (oncologist, Sun Yat-sen University Cancer Center, Guangzhou, China).
The highlight of this study is the use of immunotherapy as the first line of treatment for CNP, whereas this class of molecules is used more in the second line, commented the Dr Jared Weiss (specialist in head and neck cancers, University of North Carolina, United States).
If the FDA authorizes toripalimab in this indication, it “would change the references for the management of the three therapy modalities” he told Medscape Medical News.
Discussing during this presentation, the Dr Julie Gralow, Chief Medical Officer and Executive Vice President of ASCO, confirmed that “this was one of the first studies of relapsed or metastatic CNP to show benefit” from the combination of PD-1 inhibitor and chemotherapy .
“With authorization from the FDA, these results should induce a change in practice,” she said.
With FDA clearance, these results should lead to a change in practice.
Toripalimab, 240 mg in this trial, or placebo was given with gemcitabine and cisplatin every three weeks for up to six cycles. The administration of toripalimab or placebo was then continued every three weeks until disease progresses again, intolerable toxicity occurs or treatment has been given for two full years.
The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months versus 5.7 months in the control group.
The PFS at one year was 19.4% with toripalimab to 27.9% with placebo. Even better PFS was observed with toripalimab in the PD-L1 subgroups.
Grade 3 or more serious side effects occurred in almost 90% of participants in both groups. Adverse effects with fatal outcome occurred in just under 3% of participants in both groups.
Adverse effects leading to discontinuation of treatment affected 7.5% of patients in the toripalimab group and 4.9% of those in the control group. As would be expected with immunotherapy, immunity-related adverse reactions such as hypothyroidism were more frequently seen in the toripalimab group (39.7% vs 18.9%), as were the effects Grade 3 adverse reactions or more serious immunity-related adverse reactions (7.5% vs. 0.7%).
In the May 2020 interim analysis, the median duration of treatment was 39 weeks in the toripalimab group, 36 weeks in the placebo group.
The clinical trial was conducted in China, Taiwan and Singapore.
The JUPITER-02 trial was funded by Shanghai Junshi Bioscience. The investigators and Dr. Weiss have not declared a link of interest. Dr Gralow said ties to several companies.
Photo credit: Getty Images
The article was originally published on Medscape.com under the heading “New Drug Toripalimab Improves Survival in Nasopharyngeal Cancer ”. Translated / adapted by Marine Cygler.