According to the results from the phase III JUPITER-02 study, the addition of toripalimab, a humanized IgG4K anti–PD-1 monoclonal antibody, to standard gemcitabine/cisplatin chemotherapy as first-line treatment for patients with advanced nasopharyngeal carcinoma provided superior progression-free survival and objective response, as well as a longer duration of response, compared with combination chemotherapy alone. The findings—presented by Xu et al during the 2021 ASCO Annual Meeting (Abstract LBA2)—support the use of toripalimab with gemcitabine/cisplatin as the new standard of care for this patient population, according to the study authors.

Nasopharyngeal carcinoma, a rare tumor of the head and neck, accounts for less than one case for every 100,000 people each year in most parts of the world, including the United States. The cancer is often diagnosed at an advanced stage, and patients with early-stage disease usually relapse after radiation therapy or radiochemotherapy.

Currently, the standard of care in the first-line treatment setting for locally advanced, recurrent, or metastatic nasopharyngeal carcinoma is combination gemcitabine/cisplatin chemotherapy.

JUPITER-02 Findings

The researchers enrolled 289 patients into the randomized trial: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020, the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm.

A significant improvement in progression-free survival was detected for the toripalimab arm compared to the placebo arm (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, two-sided P = .0003), with median progression-free survival of 11.7 vs 8.0 months. The 1-year progression-free survival rates were 49% and 28%, respectively. An improvement in progression-free survival was observed across relevant subgroups, including all PD-L1 subgroups. The objective response rate was 77.4% vs 66.4% (P = .033) and the median duration of response was 10.0 vs 5.7 months (HR = 0.50, 95% CI = 0.33–0.78).

As of January 15, 2021, overall survival data was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm reported (HR = 0.68, 95% CI = 0.41–1.14, P = .14).

The incidence of grade ≥ 3 adverse events was 89.0% vs 89.5%; adverse events leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%) and fatal adverse events (2.7% vs 2.8%) were similar between the two arms. However, immune-related adverse events (39.7% vs 18.9%) and grade ≥ 3 immune-related adverse events (7.5% vs 0.7%) were more frequent in the toripalimab arm.

Clinical Significance

“The addition of toripalimab to gemcitabine/cisplatin chemotherapy as first-line treatment for  patients with advanced nasopharyngeal carcinoma provided superior progression-free survival and objective response rate and longer duration of response than gemcitabine/cisplatin alone with a manageable safety profile. These results support the use of toripalimab with gemcitabine/cisplatin chemotherapy as the new standard of care for this population,” concluded the study authors.

Julie R. Gralow, MD, FACP, FASCO

During an ASCO press briefing highlighting this study, Julie R. Gralow, MD, FACP, FASCO, ASCO Chief Medical Officer and Executive Vice President, said, “This is one of the first studies in metastatic or recurrent nasopharyngeal carcinoma to show a benefit of a combination of a PD-1 inhibitor with chemotherapy. Toripalimab is currently approved in China for several indications, including in the third-line setting for metastatic nasopharyngeal carcinoma. In the United States, it has received Breakthrough Therapy designation [from] the U.S. Food and Drug Administration (FDA) for recurrent, metastatic nasopharyngeal carcinoma, as well as Fast Track and Orphan Drug status for other cancer types. With FDA approval, these findings should prove to be practice-changing.”

Disclosure: For full disclosures of the study authors, visit coi.asco.org.