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Adding the investigational PD-1 immune checkpoint inhibitor toripalimab to standard frontline chemotherapy significantly delayed disease progression in patients with recurrent or metastatic nasopharyngeal carcinoma, a randomized trial found.

Results from the phase III JUPITER-2 trial showed that the addition of toripalimab significantly improved progression-free survival (PFS) compared with placebo, with a median 11.7 months compared with 8.0 months (HR 0.52, 95% CI 0.36-0.74, P=0.0003), reported Rui-Hua Xu, MD, PhD, of Sun Yat-Sen University Cancer Center in Guangzhou in China.

In an interim analysis of overall survival (OS), adding toripalimab to gemcitabine plus cisplatin also showed benefit over placebo (HR 0.60, 95% CI 0.36-0.99, P=0.46), said Xu, speaking at a press briefing in advance of the virtual annual meeting.

"The combination was safe, and no new safety signals were found," he said. "The results support the use of toripalimab in combination with the [gemcitabine-cisplatin] regimen as the new standard of care for first-line treatment of recurrent or metastatic nasopharynx carcinoma."

Nasopharyngeal carcinoma, which occurs in the back of the nose and above the back of the throat, occurs far more frequently in Asia, where in 2018 the disease accounted for more than 70% of the approximately 129,000 new diagnoses reported worldwide.

Although the current standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma is gemcitabine-cisplatin chemotherapy, the duration of response is typically less than 6 months. Toripalimab, a monoclonal antibody specific for PD-1, is approved in China as a monotherapy in the second- or third-line setting, where it has demonstrated durable responses in patients with recurrent/metastatic disease.

In JUPITER-2, 289 patients receiving gemcitabine-cisplatin in the first-line setting were randomized 1:1 to either toripalimab or placebo. Patients were treated with chemotherapy plus toripalimab or placebo every 3 weeks for up to six cycles, followed by toripalimab or placebo every 3 weeks until disease progression.

The 1-year PFS rate was 49.4% in the toripalimab arm compared with 27.9% in the placebo arm. OS rates at 2 years were 77.8% with toripalimab versus 63.3% with placebo.

Regarding safety, the incidence of grade ≥3 adverse events (AEs) was similar in both arms (89.0% for the toripalimab patients and 89.5% for the placebo group), Xu reported. The rate of AEs leading to discontinuation of treatment was also similar (7.5% vs 4.9%, respectively), as were fatal AEs (2.7% vs 2.8%, respectively). Immune-related AEs, however, were significantly higher in the toripalimab arm (39.7% vs 18.9%), as were immune-related grade ≥3 AEs (7.5% vs 0.7%).

ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, commented at the briefing that while treatment advances for nasopharyngeal carcinoma have lagged behind those of other cancers, toripalimab has received , as well as and for other cancer types.

"With FDA approval these findings should prove to be practice changing," she said.

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