Toripalimab plus first-line chemotherapy extends PFS in advanced nasopharyngeal carcinoma
Adding toripalimab to gemcitabine-cisplatin chemotherapy significantly improved PFS and overall response rates and induced longer-lasting responses than chemotherapy alone as first-line therapy for advanced nasopharyngeal carcinoma.
Results of the randomized, double-blind, phase 3 JUPITER-02 study, scheduled for presentation during the plenary session of the virtual ASCO Annual Meeting, also showed the combination had a manageable safety profile.
“Nasopharyngeal carcinoma is an epidemic in southern China and Southeast Asia. There remains an unmet need to improve the prognosis of these patients,” Rui-Hua Xu, MD, PhD, professor in the department of medical oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, said during a press conference. “Toripalimab is the first anti-PD-1 antibody that [showed] an improvement in the first-line treatment of nasopharyngeal carcinoma in China, with durable response and a tolerable safety profile.”
Researchers screened 408 patients at 35 sites in China, Taiwan and Singapore from November 2018 to October 2019. They enrolled 289 patients aged 18 to 75 years with advanced nasopharyngeal carcinoma who had an ECOG performance status of 0 or 1 and had not been treated with chemotherapy in the metastatic or recurrent setting.
Xu and colleagues randomly assigned the patients 1:1 to receive up to six 3-week cycles of either toripalimab (Junshi Biosciences), dosed at 240 mg (n = 146), or placebo (n = 143) on day 1 plus 1,000 mg/m2 gemcitabine on days 1 and 8 and 80 mg/m2 cisplatin on day 1. Patients continued on monotherapy (toripalimab or placebo) every 3 weeks until disease progression, excessive toxicity or 2 years of treatment.
PFS assessed by blinded independent review committee per RECIST version 1.1 served as the primary endpoint; secondary endpoints included ORR, duration of response and OS.
Researchers planned a final PFS analysis at 200 PFS events, following a prespecified interim PFS analysis at 130 PFS events. At the interim analysis cutoff date of May 30, 2020, median treatment duration was 39 weeks for the toripalimab group and 36 weeks for the placebo group.
Results showed significant improvement in PFS with the toripalimab vs. placebo regimen (HR = 0.52; 95% CI, 0.36-0.74), with median PFS of 11.7 months vs. 8 months and 1-year PFS rates of 49% vs. 28%. Researchers also observed a PFS benefit across key subgroups, including all PD-L1 subgroups.
In addition, Xu reported a higher ORR (77.4% vs. 66.4%; P = .033) and a longer median duration of response (10 months vs. 5.7 months) with toripalimab vs. placebo.
Although OS data had not yet matured, researchers observed a 40% reduction in the risk for death with toripalimab (HR = 0.603; 95% CI, 0.364-0.997).
The toripalimab group had higher rates of immune-related adverse events (any-grade, 39.7% vs. 18.9%; grade 3, 7.5% vs. 0.7%) compared with the placebo group, but other toxicity results appeared similar between the groups, including overall incidence of grade 3 or higher adverse events (89% vs. 89.5%), adverse effects leading to discontinuation of treatment (7.5% vs 4.9%) and fatal adverse effects (2.7% vs 2.8%).
The results support toripalimab with gemcitabine-cisplatin chemotherapy as a standard-of-care first-line therapy for patients with recurrent or metastatic nasopharyngeal carcinoma, according to Xu.
“Nasopharyngeal carcinoma is challenging as it is typically diagnosed in an advanced stage, when current therapy options are extremely limited,” Xu said in a press release. “The extended response in patients [who received] toripalimab marks a significant advance for treatment of this disease.”
Perspective
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This is exciting data for patients with Epstein-Barr virus (EBV)-related nasopharynx cancer. Patients with recurrent/metastatic EBV-related nasopharynx cancer have poor prognoses and not a lot of options. The addition of toripalimab, a monoclonal antibody specific for PD-1, to cytotoxic chemotherapy — gemcitabine and cisplatin — seems to improve PFS compared with chemotherapy alone. This mirrors the data for other types of head and neck cancer that have shown good responses to other anti-PD-1 agents, such as pembrolizumab (Keytruda, Merck) and nivolumab (Opdivo, Bristol Myers Squibb).
The FDA has granted breakthrough designation for toripalimab, and this data seems to confirm preliminarily a benefit for patients with EBV-related nasopharyngeal cancer. It will be interesting to see the final OS data for this study, as this will be critical to determine whether to incorporate it into daily clinical practice. Nevertheless, if there is FDA approval, this would certainly be practice-changing, although it’s too early to tell at this time. OS is the critical component that needs to be reported when complete to assess how beneficial it will be for patients.
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It is great to see immunotherapy moving into the first line for recurrent or metastatic nasopharyngeal cancer. Although nasopharyngeal cancer is a fairly chemotherapy-sensitive disease, responses can be brief with decreasing benefit from subsequent therapies, leaving significant unmet needs in this space. Similar to chemotherapy-immunotherapy combinations in other cancer types, we see in this study increased response rates with an expected increase in immune-related adverse events and comparable serious adverse events.
It is encouraging to see a greater than 20% increase in 1-year PFS, which is hopefully indicative of a population of patients who will derive prolonged benefit, as well as PFS benefit across all PD-L1 subgroups.
I look forward to seeing more mature data with OS results and more granular breakdown of subgroups; but, this likely ushers in the advent of chemotherapy-immunotherapy as standard of care in this setting.
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Xu, R-H, et al. Abstract LBA2. Scheduled for presentation at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.