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 of research in recurrent or metastatic nasopharyngeal carcinoma. Phase I and II trials have evaluated nivolumab, pembrolizumab, atezolizumab, spartalizumab, tislelizumab, and camrelizumab in this setting, finding median progression-free survivals ranging from 2 months to more than 6.5 months and median overall survivals extending beyond 17 months. Ongoing phase III trials are evaluating pembrolizumab monotherapy and toripalimb, camrelizumab, and nivolumab in combination with gemcitabine/cisplatin.

“JUPITER-02 shows a highly encouraging progression-free survival benefit with toripalimab plus gemcitabine/cisplatin as first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” Dr. Chan commented. However, he said, there remain open questions.

Questions Remain

“When you look at the curves more closely, you can see that for the initial 5 months, they overlap completely. They begin to separate at the time the systemic therapy is stopped and maintenance toripalimab begins (vs placebo in the chemotherapy arm),” Dr. Chan pointed out. “Whether the improvement with toripalimab over placebo can still be achieved by using maintenance systemic chemotherapy is obviously an open question.” Active maintenance might also explain the effect on overall survival, he added.

“Maintenance is not considered standard, but in fact, a lot of us give it to patients who can tolerate it. We know that patients with undifferentiated nasopharyngeal carcinoma tend to have a relatively short progression-free survival when we stop treatment, so this needs to be tested,” said Dr. Chan. “Preliminary data suggest that maintenance toripalimab is beneficial, and the role of maintenance systemic therapy remains to be defined.”

JUPITER-02 also showed the benefit of toripalimab across all subgroups, including both PD-L1–positive and PD-L1–negative patients. “This is a somewhat surprising finding,” he said. “In most studies, PD-L1–positive patients benefit more, whereas in this study, numerically the hazard ratio was more significant for the PD-L1–negative patients (0.35 vs 0.59). We need more in-depth study to explain this.”

JUPITER-02’s findings “may be practice-changing if they are confirmed by an overall survival benefit in an adequately powered study. Meanwhile, gemcitabine/cisplatin remains the standard of care in the first line,” he said.

Moving Forward

A better understanding of the role of PD-L1 as well as tumor mutational burden and dynamic clearance of Epstein-Barr virus (EBV) will come from the future biomarker analysis. “There is potential for dynamic biomarkers like EBV DNA, or circulating tumor DNA, to guide the optimal sequence of treatments,” Dr. Chan said.

According to Dr. Chan, future treatments will undoubtedly involve immunotherapy combinations. Not only will such agents be paired with chemotherapy but with other immunotherapeutics and with signaling inhibitors, bispecific antibodies, and antibody-drug conjugates. 

DISCLOSURE: Dr. Chan has an immediate family member who holds stock or other ownership interests in CSPC Pharmaceutical Group Ltd and WuXi Biologics; has received honoraria from BeiGene, Merck Serono, Merck Sharp & Dohme, and Tessa Therapeutics; has served as a consultant or advisor to Merck Serono, Merck Sharp & Dohme, and Tessa Therapeutics; has received research funding from Merck Serono, Merck Sharp & Dohme, Novartis, and Pfizer; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.