What is the role of Toripalimab (generic name: not specified, assuming it refers to the monoclonal antibody) in cancer treatment?

Role of Toripalimab in Cancer Treatment

Toripalimab should be offered in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC), regardless of PD-L1 expression levels, based on significant improvements in progression-free survival and overall survival. 1

Toripalimab in Nasopharyngeal Carcinoma

First-Line Treatment

• Toripalimab is a humanized IgG4K monoclonal antibody against PD-1 that has demonstrated significant clinical benefit in NPC treatment 1
• The JUPITER-02 phase III trial showed:
  • Significantly improved progression-free survival (PFS) with toripalimab plus gemcitabine-cisplatin compared to chemotherapy alone (11.7 vs 8.0 months; HR 0.52) 1
  • 40% reduction in mortality risk (HR 0.603) 1
  • Benefit observed regardless of PD-L1 expression status 1
  • Median overall survival not reached in the toripalimab group vs 33.7 months in the placebo group 2

Second-Line Treatment

• In previously treated recurrent or metastatic NPC, toripalimab monotherapy showed:
  • Objective response rate (ORR) of 20.5% with median duration of response of 12.8 months 3
  • Higher ORR (23.9%) in patients who failed at least two lines of systemic chemotherapy 3
  • Patients with ≥50% decrease in plasma EBV DNA copy number by day 28 had significantly better response rates (48.3% vs 5.7%) 3

Treatment Algorithm for NPC

1. First-line treatment for recurrent/metastatic NPC:

   • Toripalimab (240 mg) + gemcitabine (1,000 mg/m² days 1 and 8) + cisplatin (80 mg/m² day 1) every 21 days for up to 6 cycles
   • Followed by maintenance toripalimab for up to 2 years 1, 2

2. Second-line treatment options:

   • Toripalimab monotherapy (3 mg/kg every 2 weeks) for patients who progressed on platinum-based therapy 3
   • Alternative PD-1 inhibitors (nivolumab, pembrolizumab) may also be considered 1, 4

Toripalimab in Other Cancers

Locoregionally Advanced NPC

• A "sandwich approach" with neoadjuvant and adjuvant toripalimab combined with concurrent chemoradiotherapy has shown promising results:
  • Improved 2-year PFS (92.0% vs 74.0%; HR 0.40) compared to placebo 5
  • Particularly beneficial for patients with high pretreatment plasma EBV DNA 5

Esophageal Squamous Cell Carcinoma

• Toripalimab combined with definitive chemoradiotherapy in locally advanced disease showed:
  • Complete response rate of 62% at 3 months after radiotherapy 6
  • 1-year overall survival of 78.4% 6

Other Malignancies

• Early phase studies have shown activity in various solid tumors and lymphomas:
  • Particularly promising results in alveolar soft part sarcoma (ASPS) and lymphoma 7
  • Objective response rate of 90.9% in lymphoma patients 7

Safety Profile

• Most common adverse events with toripalimab include:

  • Immune-related adverse events (54.1% vs 21.7% with placebo) 2
  • Grade 3 or greater immune-related adverse events (9.6% vs 1.4% with placebo) 2
  • Higher discontinuation rate compared to placebo (11.6% vs 4.9%) 2

• Important monitoring considerations:

  • Regular assessment for immune-related toxicities
  • Monitoring of EBV DNA levels as a potential biomarker of response 3

Clinical Pearls and Caveats

• Early decrease in plasma EBV DNA copy number correlates with favorable response to toripalimab 3
• Tumor mutational burden appears to have limited predictive value for response in NPC 3
• Patients with genomic amplification in 11q13 region or ETV6 genomic alterations may have poor responses to toripalimab 3
• Consider toripalimab's role in multimodal approaches for locally advanced disease, not just in the metastatic setting 5

The evidence strongly supports toripalimab as a standard of care in combination with chemotherapy for recurrent or metastatic NPC, with emerging evidence for its use in other cancer types and treatment settings.