What is the preferred treatment option between tislelizumab (anti-PD-1 antibody) and toripalimab (anti-PD-1 antibody) for a patient with extensive small cell carcinoma of the lung?

Tislelizumab vs Toripalimab for Extensive Small Cell Lung Cancer

Neither tislelizumab nor toripalimab are recommended as first-line treatment for extensive-stage small cell lung cancer based on current evidence-based guidelines. The NCCN Category 1 preferred regimens are atezolizumab or durvalumab combined with platinum-etoposide chemotherapy, which have demonstrated superior overall survival in phase 3 trials 1.

Guideline-Recommended First-Line Therapy

The standard of care for extensive-stage SCLC is carboplatin plus etoposide plus either atezolizumab (Category 1) or durvalumab (Category 1), followed by maintenance immunotherapy 1.

Atezolizumab Plus Chemotherapy

• Median OS: 12.3 months vs 10.3 months with chemotherapy alone (HR 0.76, p=0.0154) 1
• 1-year OS rate: 51.9% vs 39.0% with chemotherapy alone 1
• FDA-approved dosing: 1,200 mg maintenance atezolizumab (Category 1 recommendation) 1
• Grade 3-4 adverse events: 67.7% vs 63.3% with chemotherapy alone 1

Durvalumab Plus Chemotherapy

• Median OS: 13.0 months vs 10.3 months with chemotherapy alone (HR 0.73, p=0.0047) 1
• 1-year OS rate: 52.8% vs 39.3% with chemotherapy alone 1
• Serious adverse events: 32% vs 36% with chemotherapy alone 1

Evidence for Tislelizumab in SCLC

Tislelizumab has limited evidence in extensive-stage SCLC and is NOT included in NCCN or ESMO guidelines for this indication 1.

Available Data

• Phase 2 study (n=17 SCLC patients): ORR 77%, median PFS 6.9 months, median OS 15.6 months when combined with etoposide plus platinum 2
• This was a small, single-arm phase 2 study without a control arm, providing insufficient evidence for guideline inclusion 2
• Tislelizumab is approved in China for NSCLC but NOT for SCLC 1

Safety Profile

• Common adverse events: anemia (79.6%), decreased white blood cell count (74.1%) 2
• Treatment discontinuation due to adverse events: 12.5-29.7% depending on chemotherapy regimen 3
• No deaths solely attributed to tislelizumab in phase 3 NSCLC trials 3

Evidence for Toripalimab in SCLC

Toripalimab has even more limited evidence in SCLC and is NOT included in any major international guidelines 1.

Available Data

• CHOICE-01 trial data mentioned for NSCLC only: median PFS 8.3 months vs 5.6 months with chemotherapy alone 1
• No specific SCLC data provided in the evidence 1
• Toripalimab is approved in China for NSCLC but NOT for SCLC 1

Critical Pitfalls to Avoid

Do not use pembrolizumab in extensive-stage SCLC - a phase 3 trial demonstrated that pembrolizumab plus etoposide and platinum did NOT improve OS compared with chemotherapy alone 1.

Do not use ipilimumab in extensive-stage SCLC - addition of ipilimumab to etoposide and platinum did not improve OS or PFS 1.

Do not delay treatment with proven therapies - atezolizumab and durvalumab have Category 1 evidence with demonstrated mortality benefit, while tislelizumab and toripalimab lack phase 3 data in SCLC 1.

Clinical Decision Algorithm

1. First-line extensive-stage SCLC with PS 0-1: Use carboplatin + etoposide + atezolizumab OR carboplatin/cisplatin + etoposide + durvalumab 1

2. If immunotherapy contraindicated: Use platinum + etoposide alone for 4-6 cycles 1

3. If considering tislelizumab or toripalimab: These agents should only be used in the context of clinical trials or when guideline-recommended therapies are unavailable, as they lack phase 3 evidence in SCLC 1

4. Geographic considerations: In China, where tislelizumab is approved for NSCLC, it may be considered off-label for SCLC only after discussion of limited evidence and when standard therapies are unavailable 1, 2