EXTENTORCH trial

Background

Phase III, double-blind, placebo-controlled RCT (EXTENTORCH), 51 China centers. N=490 treatment-naive extensive-stage SCLC (ES-SCLC). Tested adding the anti–PD-1 antibody toripalimab to first-line etoposide-platinum chemotherapy.

Interventions and follow up

Arm A: Toripalimab 240 mg IV Q3W + etoposide 100 mg/m² Days 1–3 + cisplatin/carboplatin Q3W × 4–6 cycles → toripalimab maintenance Q3W.
Arm B: Placebo IV Q3W + same chemo → placebo maintenance.
Primary endpoint: PFS (investigator) and OS.
mFollow up: ~18mo

Results

PFS: 5.7 vs 4.3mo, HR 0.65, 95% CI 0.53–0.79, P<.001
OS: 14.6 vs 13.3mo, HR 0.67, 95% CI 0.52–0.86, P=.002
1yr OS: 60% vs 40%
ORR: 72% vs 62%
CR: 2.3% vs 1.3%
Biomarkers (WES, n=300): low intratumor heterogeneity, HLA-A11+/HLA-B62- haplotype, wild-type KMT2D and COL4A4, or CTNNA2/SCN4A variants correlated with favorable PFS/OS with toripalimab

Adverse events

Overall: Grade ≥3 AEs 74% vs 67%.
Hematologic: predominant grade ≥3 events (neutropenia, anemia, thrombocytopenia).
Immune-related: hypothyroidism ~20% with toripalimab, mostly grade 1–2.

Conclusions

Adding toripalimab to first-line etoposide-platinum significantly improved both PFS and OS in ES-SCLC, consistent with other PD-(L)1 inhibitors, supporting chemoimmunotherapy as a standard of care where toripalimab is available.

Key Limitations

Exclusively Chinese population limits generalizability. Modest absolute PFS gain (~1.4mo). Investigator-assessed PFS (no BICR for primary). Biomarker findings exploratory and hypothesis-generating. No PD-L1 stratification or required brain imaging detail.

Clinical Context

China NMPA approved toripalimab + chemo for first-line ES-SCLC in 2024; not FDA-approved for this indication. Joins atezolizumab (IMpower133) and durvalumab (CASPIAN) as first-line chemo-IO options; ESMO endorses adding PD-(L)1 to platinum-etoposide in ES-SCLC.

References