1. Fuerst, Mark L.

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The addition of the immunotherapy agent toripalimab to standard first-line chemotherapy significantly delays disease progression for patients with recurrent or metastatic nasopharyngeal carcinoma (NPC). The Phase III international study may represent a paradigm shift in the care of these patients who currently have few treatment options.

Nasopharyngeal Carci... - Click to enlarge in new windowNasopharyngeal Carcinoma. Nasopharyngeal Carcinoma

NPC, a type of head and neck cancer that starts in the nasopharynx, represents a significant global health problem. The cancer is an endemic malignancy in East and Southeast Asia, and accounts for more than 70 percent of the approximate 129,000 new diagnoses worldwide in 2018. Gemcitabine plus cisplatin is currently the standard first-line treatment for recurrent or metastatic NPC. However, the duration of response is, on average, less than 6 months.


"There remains an unmet medical need to improve the prognosis in these patients," said Rui-hua Xu, MD, PhD, of the Department of Medical Oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, at a press briefing during the 2021 ASCO Annual Meeting.


Toripalimab is the first anti-programmed cell death-1 (PD-1) antibody approved for third-line treatment of relapsed or metastatic NPC in February 2021 in China, with durable response and tolerable safety profile, he noted. "NPC is challenging as it is typically diagnosed in an advanced stage when current therapy options are extremely limited. The extended response in patients who received toripalimab marks a significant advance for treatment of this disease," said Xu.


About the Study

JUPITER-02 is a global, double-blind, placebo-controlled, Phase III study evaluating gemcitabine plus cisplatin chemotherapy in combination with toripalimab or placebo as first-line treatment in patients with recurrent or metastatic NPC (Abstract LBA2).


The trial enrolled 289 patients with recurrent or metastatic NPC who had not received previous chemotherapy. Patients were randomized to receive toripalimab 240 mg (146 patients) or placebo (143 patients) every 3 weeks for up to 6 cycles. Patients in both groups also received gemcitabine/cisplatin chemotherapy. The study's primary endpoint was PFS in all study patients. Secondary endpoints included overall response rate, duration of response, and overall survival (OS).


Key Findings

The JUPITER-02 trial demonstrated that the addition of the immunotherapy toripalimab to standard first-line chemotherapy lengthened the time to disease progression compared with placebo, with a median of 11.7 months versus 8 months, respectively. At 1 year, 49 percent of patients who received toripalimab had not experienced disease progression, compared to 28 percent of those who received placebo.


"Efficacy results show a significant improvement in PFS for the toripalimab arm compared to the placebo arm," said Xu. "The hazard ratio for PFS was 0.52."


OS was not mature at this interim analysis. The 1-year OS for the toripalimab arm was 91.6 percent versus 87.1 percent in the placebo arm. The 2-year OS rate was 77.8 percent and 63.3 percent, respectively. "At 9 months of the interim analysis, we observed a 40 percent reduction in the risk of death in the toripalimab arm," noted Xu.


The most common adverse events were hematological toxicities, which were mainly attributed to the gemcitabine-cisplatin chemotherapy regimen. Serious adverse events grade 3 or greater were similar for both groups-89 percent for toripalimab versus 89.5 percent for placebo, with discontinuation of treatment in 7.5 percent of immunotherapy patients, compared to 4.9 percent on placebo. Fatal adverse events were similar between the two arms, 2.7 percent and 2.8 percent, respectively.


Immune-related adverse events were more common with toripalimab, 39.7 percent, compared with placebo, 18.9 percent. Immune-related adverse events grade 3 or greater were also more common with toripalimab (7.5%) than with placebo (0.7%), which were expected and manageable, he said.


In conclusion, Xu said: "We can see that toripalimab added to gemcitabine and cisplatin showed better PFS and OS than chemotherapy alone. The combination was safe and no new safety signals were found. These results support the use of toripalimab in combination with the gemcitabine plus cisplatin regimen as the new standard of care for the first-line treatment of recurrent or metastatic NPC."


ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, the Jill Bennett Endowed Professor of Breast Medical Oncology and Professor of Global Health at the University of Washington School of Medicine, commented: "NPC is a public health problem, particularly in East and Southeast Asia. In the U.S., toripalimab has received breakthrough therapy designation by the FDA for recurrent or metastatic NPC, as well as fast-track and orphan drug status for other cancer types. With FDA approval, these findings should prove to be practice-changing."


Mark L. Fuerst is a contributing writer.