Toripalimab Added to Chemotherapy Extends PFS in Nasopharyngeal Carcinoma

Results from the phase 3 JUPITER-02 trial show that oncologists can extend progression-free survival in patients with nasopharyngeal carcinoma by adding toripalimab to chemotherapy.

Adding the PD-1 monoclonal antibody toripalimab to standard chemotherapy for patients with nasopharyngeal carcinoma boosted progression-free survival (PFS) compared to chemotherapy alone in the phase 3 JUPITER-02 trial.

When added to standard-of-care gemcitabine plus cisplatin, toripalimab (Tuoyi) outperformed standard of care plus placebo in patients with metastatic nasopharyngeal carcinoma as a first-line treatment, findings from the phase 3 JUPITER-02 trial showed.

Patients who received the investigational anti-PD-1 monoclonal antibody experienced a median progression-free survival (PFS) of 11.7 versus 8.0 months (Hazard Ratio [HR], 0.52; 95% Confidence Interval [CI] 0.36–0.74), P =.0003). Key subgroups, including the roughly 75% of patients with PD-L1 expression, displayed improved PFS, too. These interim results were published recently in Nature Medicine.1

Led by Hai-Qiang Mai, MD, PhD, of Sun Yat-Sen University Cancer Center in Guangzhou, China, the authors concluded, “The addition of toripalimab to GP [gemcitabine plus cisplatin] chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma provided superior PFS compared to GP alone, and with a manageable safety profile.”

In JUPITER-02, an international, double-blind phase 3 trial (NCT 03581786), 289 chemotherapy-naïve patients with recurrent or metastatic nasopharyngeal carcinoma were randomized. A total of 146 patients were assigned to the toripalimab combination arm, while 143 were assigned to the placebo arm. 

The trial design called for at least 6 treatment cycles on a 3-week schedule. Following chemotherapy completion, nearly 80% of patients continued with maintenance therapy of either toripalimab or placebo. At data cutoff in May 2020, patients in the experimental group had received a median of 12 cycles, while those in the placebo group had received a median of 11 cycles.

JUPITER-02’s primary end point was PFS as assessed by a blinded central review committee. Secondary end points included overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and safety. OS data remain immature, but, as of February 2021, investigators observed a 40% reduction in risk of death in the toripalimab arm compared to the placebo arm (HR, 0.603; 95% CI, 0.364-0.997). 

A notable number of patients in both arms achieved a complete response (CR): 28 in the toripalimab group (19.2%) and 16 in the placebo group (11.2%). A slight majority of patients achieved a partial response: 85 patients in the toripalimab arm (58.2%) and 79 (55.2%) in the placebo arm. The ORR was significantly higher in the toripalimab arm (77.4%; 95% CI, 69.8–83.9) than in the placebo arm (HR, 66.4%; 95% CI, 58.1-74.1; P =.0335). The DCR was 87.7% (95% CI, 81.2-92.5) in the toripalimab arm and 79.7% (95% CI, 72.2–86.0) in the placebo arm.

All patients experienced at least one treatment-related adverse event (TRAE). Leukopenia, anemia, and neutropenia were the most common and likely, the investigators wrote, stemmed from the chemotherapy. TRAEs seen more frequently in the experimental arm include hypothyroidism (30.8% vs 16.8%), pruritis (16.4% vs 7.0%) and pneumonia (16.4% vs 6.3%). Serious AEs were comparable between the two arms, but immune-related AEs (39.7% versus 18.9%) and grade ≥3 infusion reactions (7.5% versus 0.7%) were seen more frequently in the toripalimab arm.

In discussing the importance of their work, Mai et al. emphasized that, although nasopharyngeal carcinoma is a rare malignancy in most of the world, its incidence rate in China is 3.0 per 100,000 people. All of JUPITER-02’s study patients were Asian and nearly all had nonkeratinizing nasopharyngeal carcinoma, the predominant subtype in Asia and the most common form of this malignancy in North America. They noted that this subtype’s strong association with Epstein-Barr virus and nonsurgical treatment paradigm has led to its frequent exclusion from clinical trials of head and neck cancer, resulting in unmet need for these patients. “We believe the results observed in JUPITER-02 can be extrapolated to Western populations, because the majority of patients with NPC in the West and China/Southeast Asia have the nonkeratinizing histology,” they wrote.

The FDA granted toripalimab a breakthrough therapy designation in September 2020. Toripalimab first received approval for the second-line treatment of metastatic melanoma the National Medical Product Administration (NMPA) in China in December 2018. Then the NMPA awarded conditional approval of toripalimab for the third-line

treatment of recurrent and metastatic nasopharyngeal carcinoma in February 2021 by the NMPA.

References:

1. Mai HQ, Chen QY, Chen D, et al. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. Published online August 2, 2021. https://doi.org/10.1038/s41591-021-01444-0 

2. News Release: NMPA Approves Toripalimab in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma after Failure of at Least Two Lines of Prior Systemic Therapy. Global Newswire. February 21, 2021. Accessed November 29, 2021. https://www.globenewswire.com/en/news-release/2021/02/21/2179175/0/en/NMPA-Approves-Toripalimab-in-Patients-with-Recurrent-or-Metastatic-Nasopharyngeal-Carcinoma-after-Failure-of-at-Least-Two-Lines-of-Prior-Systemic-Therapy.html