Background
Global, randomised, placebo-controlled phase 3 trial (SKYSCRAPER-07; 166 centres, 28 countries). N=760. Unresectable stage II–IVA (and selected IVB) oesophageal squamous cell carcinoma (ESCC) after definitive concurrent chemoradiotherapy (dCRT). Three-arm design testing atezolizumab ± tiragolumab (anti-TIGIT) consolidation.
Results
INTERVENTIONS AND FOLLOW UP: Arm A: atezolizumab 1200 mg + tiragolumab 600 mg IV Q3W ×17 cycles (n=257).
Arm B: atezolizumab 1200 mg + placebo IV Q3W ×17 cycles (n=250).
Arm C: placebo + placebo (n=253).
Primary endpoints (hierarchical): investigator-assessed PFS then OS for atezo+tira vs placebo, then OS for atezo vs placebo.
mFollow up: 25.0 months.
RESULTS: PFS (atezo+tira vs placebo): HR 0.82, 95% CI 0.65–1.03, P=.0947 — not met.
OS (atezo+tira vs placebo): HR 0.91, 95% CI 0.70–1.18, descriptive P=.4772 (NS).
OS (atezo vs placebo): HR 0.69, 95% CI 0.52–0.91, descriptive P=.0085.
PFS (atezo vs placebo): HR 0.74, 95% CI 0.58–0.93.
Arm B: atezolizumab 1200 mg + placebo IV Q3W ×17 cycles (n=250).
Arm C: placebo + placebo (n=253).
Primary endpoints (hierarchical): investigator-assessed PFS then OS for atezo+tira vs placebo, then OS for atezo vs placebo.
mFollow up: 25.0 months.
RESULTS: PFS (atezo+tira vs placebo): HR 0.82, 95% CI 0.65–1.03, P=.0947 — not met.
OS (atezo+tira vs placebo): HR 0.91, 95% CI 0.70–1.18, descriptive P=.4772 (NS).
OS (atezo vs placebo): HR 0.69, 95% CI 0.52–0.91, descriptive P=.0085.
PFS (atezo vs placebo): HR 0.74, 95% CI 0.58–0.93.
Adverse events
TRAE (any): 74.8% (atezo+tira) vs 65.2% (atezo) vs 55.4% (placebo).
Treatment-related deaths: 1.2% vs 0.8% vs 1.6%.
Treatment-related deaths: 1.2% vs 0.8% vs 1.6%.
Conclusions
The primary comparison (atezolizumab+tiragolumab vs placebo) was NOT met. However, atezolizumab monotherapy consolidation after dCRT significantly improved OS and PFS vs placebo in unresectable ESCC — the first positive checkpoint-inhibitor consolidation signal in this setting. Adding tiragolumab provided no benefit.
Key Limitations
The positive atezolizumab-vs-placebo OS is a lower-hierarchy comparison reported descriptively (formal significance constrained by the failed primary), so it is hypothesis-generating rather than confirmatory; predominantly Asian population (62.8%); the negative anti-TIGIT arm is consistent with prior tiragolumab phase 3 failures.
Clinical Context
There is no established checkpoint-inhibitor consolidation standard after dCRT for unresectable ESCC (unlike durvalumab after chemoradiotherapy in stage III NSCLC). SKYSCRAPER-07 positions atezolizumab consolidation as a promising option pending regulatory and guideline review; the tiragolumab result adds to multiple negative anti-TIGIT phase 3 trials. Not currently FDA/EMA approved in this setting.