Toripalimab Plus Chemo Stands Alone as Preferred Frontline Regimen in Updated NCCN Guidelines for Advanced Nasopharyngeal Carcinoma

The updated 2025 version of the National Comprehensive Cancer Network (NCCN) Guidelines for head and neck cancers now lists toripalimab-tpzi (Loqtorzi) in combination with cisplatin and gemcitabine as the lone preferred first-line treatment regimen for patients with recurrent, unresectable, oligometastatic, or metastatic nasopharyngeal carcinoma (NPC) where surgery and radiotherapy are not options.¹

Additionally, toripalimab monotherapy is listed as the lone preferred option in subsequent lines of therapy for patients in this population who experience disease progression on or after platinum-based chemotherapy.

Changes in the NCCN Guidelines Version 1.2025 for Cancer of the Nasopharynx in the recurrent, unresectable, oligometastatic, or metastatic setting include shifting cisplatin plus gemcitabine with or without another PD-1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) to other recommended regimens under first-line combinations.

The combination of tislelizumab-jsgr (Tevimbra), cisplatin, and gemcitabine was added to other recommended regimens under first-line combination therapies. Tislelizumab monotherapy was also added as another recommended regimen under subsequent-line immunotherapy.

Other updates to the cancer of the nasopharynx guidelines include:

• Next-generation sequencing profiling and other appropriate biomarker testing to test for at least combined positive score and tumor mutational burden prior to treatment was recommended.
• The use of maintenance capecitabine without concurrent radiotherapy following induction chemotherapy for patients with M1 oligometastatic disease and an ECOG performance status of 0 to 1 was added as useful in certain circumstances.
• Cisplatin plus radiotherapy followed by capecitabine with or without induction chemotherapy (for EBV-associated disease) was moved from other recommended regimens to useful in certain circumstances and revised for T4, N1-3 or any T, N2-3 disease.

In October 2023, the FDA approved toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent locally advanced NPC; and as monotherapy for the treatment of adult patients with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy.²

The approvals were based on finding from the phase 3 JUPITER-02 trial (NCT03581786) and the phase 2 POLARIS-02 trial (NCT02915432) for the upfront combination and later-line monotherapy indications, respectively.

In JUPITER-02, patients treated with toripalimab plus cisplatin and gemcitabine experienced a median progression-free survival (PFS) of 11.7 months compared with 8.0 months for those given placebo plus chemotherapy (HR; 0.52; 95% CI, 0.36-0.74; P = .0003). The median overall survival (OS) was not reached (NR; 95% CI, 38.7-not estimable [NE]) for the toripalimab arm vs 33.7 months (95% CI, 27.0-44.2) for the placebo arm (HR, 0.63; 95% CI, 0.45-0.89; P = .0083).

The randomized, multicenter, single-region, double-blind, placebo-controlled trial enrolled 289 patients with metastatic or recurrent, locally advanced NPC who did not receive prior treatment with systemic chemotherapy in the recurrent or metastatic setting.

Patients were randomly assigned 1:1 to received toripalimab in combination with cisplatin and gemcitabine, followed by toripalimab monotherapy; or placebo plus cisplatin and gemcitabine, followed by placebo monotherapy.

PFS served as the trial’s primary end point, and OS was a key secondary end point.

Data from the open-label, multicenter, single country, multicohort POLARIS-02 trial demonstrated that patients with previously treated unresectable or metastatic NPC treated with toripalimab monotherapy (n = 172) achieved an overall response rate (ORR) or 21% (95% CI, 15%-28%) and a median duration of response (DOR) of 14.9 months (95% CI, 10.3-NE).

The study enrolled patients with unresectable or metastatic NPC who received prior platinum-based chemotherapy; or those who experienced disease progression within 6 months of receiving platinum-based chemotherapy in neoadjuvant or adjuvant settings, or as a part of definitive chemoradiation in the locally advanced setting.

All enrolled patients received single-agent toripalimab until disease progression or unacceptable toxicity.

Regarding the safety data for toripalimab from JUPITER-02 and POLARIS-02, the most common adverse effects (AEs) reported in at least 20% of patients treated with toripalimab plus cisplatin and gemcitabine included nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise. In those treated with toripalimab alone, the most common AEs that occurred in at least 20% of patients consisted of fatigue, hypothyroidism, and musculoskeletal pain.

References

1. NCCN clinical practice guidelines in oncology (NCCN guidelines): head and neck cancers version 1.2025. NCCN. November 26, 2024. Accessed December 4, 2024. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
2. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA. October 27, 2023. Accessed December 4, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma