A new first-line standard of care may be emerging for recurrent or metastatic nasopharyngeal carcinoma, based on the findings of the global phase III JUPITER-02 trial presented at the 2021 ASCO Annual Meeting by investigators from China.1
In the study, toripalimab, an anti–PD-1 monoclonal antibody, was given in combination with gemcitabine/cisplatin, the current standard treatment. In a previous study in the second line, POLARIS-2, toripalimab monotherapy conveyed a durable response duration of nearly 13 months.2
“Though median overall survival is not mature in either arm, a 40% reduction in the risk of death was observed with toripalimab plus chemotherapy.”— RUI-HUA XU, MD
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“The addition of toripalimab to gemcitabine/cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma showed better progression-free survival, objective response rates, and duration of response than chemotherapy alone,” said Rui-hua Xu, MD, President of Medical Oncology at Sun Yat-sen University Cancer Center, Guangzhou, China. “And though median overall survival is not mature in either arm, a 40% reduction in the risk of death was observed with toripalimab plus chemotherapy. These results suggest this regimen represents a new standard of care.”
Breakthrough Status for Toripalimab
As Dr. Xu pointed out, nasopharyngeal carcinoma is an “endemic” malignancy in Southern China and Southeast Asia, with an incidence rate of 3.0 per 100,000, as compared with 1.2 per 100,000 elsewhere in the world. Treatment options for recurrent or metastatic disease have been limited.
“This is one of the first trials in recurrent and metastatic nasopharyngeal carcinoma to show the benefit of combining a PD-1 inhibitor with chemotherapy,” Julie R. Gralow, MD, ASCO Chief Medical Officer and Executive Vice President, said in a press briefing preceding the meeting.
“This is one of the first trials in recurrent and metastatic nasopharyngeal carcinoma to show the benefit of combining a PD-1 inhibitor with chemotherapy.”— JULIE R. GRALOW, MD
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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 by the U.S. Food and Drug Administration (FDA) for recurrent or metastatic nasopharyngeal carcinoma as well as Fast Track and Orphan Drug status for other cancer types (mucosal melanoma, soft-tissue sarcoma). “With these study results, following FDA approval, these findings should prove to be practice-changing,” Dr. Gralow commented.
Ongoing or completed trials are evaluating toripalimab for a broad range of other tumor types, including cancers of the lung, esophagus, stomach, bladder, breast, liver, kidney, and skin.
Significant Improvements in Disease-free Survival
The double-blind, placebo-controlled phase III trial enrolled 289 treatment-naive patients with recurrent or metastatic nasopharyngeal carcinoma; they were randomly assigned to receive gemcitabine at 1,000 mg/m2 plus cisplatin at 80 mg/m2 and toripalimab at 240 mg or placebo every 3 weeks for up to six cycles. The toripalimab arm also received maintenance toripalimab given every 3 weeks. The primary outcome was progression-free survival by blinded independent review.
Median progression-free survival was 11.7 months with toripalimab/chemotherapy vs 8.0 months with chemotherapy alone (hazard ratio [HR] = 0.52; P = .0003); the 1-year progression-free survival rates were 49.4% and 27.9%, respectively. Per investigator assessment, median progression-free survival was not reached with toripalimab/chemotherapy and was 8.0 months with chemotherapy alone (HR = 0.41; P < .0001). Benefit was seen across all key subgroups.
“The stopping boundary for efficacy was crossed at the progression-free survival analysis,” Dr. Xu said. “Therefore, the data safety monitoring committee recommended unblinding the study.”
Overall survival data remain immature. The 1-year overall survival rates were 91.6% in the experimental arm vs 87.1% in the control arm (HR = 0.603; P = .0462). The objective response rate was 77.4% with the combination and 66.4% with chemotherapy alone (P = .033), with median durations of response of 10.0 vs 5.7 months, respectively (HR = 0.50; P = .0014).
Aside from immune-related adverse events, the safety profiles of the experimental arm and control arm were similar. Adverse events grade 3 or higher related to the study drug were observed in 89% of each arm. The most common adverse events, for the experimental vs control arms, were leukopenia (62% vs 58%), anemia (47% vs 40%), neutropenia (57% vs 64%), and thrombocytopenia (33% vs 29%). Hypothyroidism of any grade, an immune-related effect, was more common with toripalimab (31% vs 17%).
Similar Benefits Found With Camrelizumab
In the press briefing, Dr. Gralow indicated that toripalimab may not be the only new agent in recurrent or metastatic nasopharyngeal carcinoma. “Another PD-1 inhibitor being developed in China—camrelizumab—is showing similar results to toripalimab, so there is potentially an additional PD-1 inhibitor with very positive results,” she commented.
Li Zhang, MD, also of Sun Yat-sen University Cancer Center, and colleagues presented results from their first-line, phase III trial of camrelizumab (CAPTINE-1st study), with a design similar to JUPITER-02.3 Camrelizumab plus gemcitabine and cisplatin, by independent review, yielded a median progression-free survival of 10.8 months vs 6.9 months with placebo plus gemcitabine and ciplatin chemotherapy alone (HR = 0.51; P < .0001) in patients with recurrent or metastatic nasopharyngeal carcinoma. Median overall survival was not reached with camrelizumab/chemotherapy and was 22.6 months with chemotherapy alone (HR = 0.67). Responses were observed in 88.1% and 80.6%, respectively, with median durations of response of 9.9 and 5.7 months, respectively.
Li Zhang, MD
Camrelizumab has been approved by the National Medical Products Association in China (formerly, the China FDA) for the indication of first-line treatment of advanced nasopharyngeal carcinoma in combination with the gemcitabine/cisplatin regimen based on this phase III study. It is also the first indication officially approved by drug regulatory authorities worldwide for this indication. According to Dr. Zhang, the study has also been accepted for publication by Lancet Oncology.
DISCLOSURE: Dr. Xu has served as a consultant or advisor to Bristol Myers Squibb, Merck Serono, Roche, Astellas, and AstraZeneca. Dr. Gralow has served as a consultant or advisor to AstraZeneca, Genentech, Genomic Health, Immunomedics, Merck, Novartis, Pfizer, Puma Biotechnology, and Sandoz. Dr. Zhang reported no conflicts of interest.
1. Xu RH, Mai HQ, Chen QY, et al: JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. 2021 ASCO Annual Meeting. Abstract LBA2. Presented June 6, 2021.
2. Wang FH, Wei XL, Feng J, et al: Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: A phase II clinical trial (POLARIS-02). J Clin Oncol 39:704-712, 2021.
3. Zhang L, Yang Y, Qu S, et al: Camrelizumab versus placebo combined with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma: A randomized, double-blind phase III trial. 2021 ASCO Annual Meeting. Abstract 6000. Presented June 7, 2021.
The invited discussant of the JUPITER-02 study was Anthony TC Chan, MD, the Li Shu Fan Medical Foundation Professor of Clinical Oncology at Hong King Cancer Institute and Sir YK Pao Centre for Cancer at the Chinese University of Hong Kong.
He noted that anti–PD-1/L1 therapies are at the forefront...