SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer

J Clin Oncol. 2024 Jan 20;42(3):324-335. doi: 10.1200/JCO.23.01363. Epub 2023 Nov 17.

Abstract

Purpose: The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.

Methods: Patients received tiragolumab 600 mg/placebo, plus atezolizumab 1,200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab. Primary end points were investigator-assessed PFS and OS in patients without history/presence of brain metastases (primary analysis set [PAS]). Additional end points included PFS and OS in all patients regardless of brain metastases status (full analysis set [FAS]), response, and safety.

Results: Four hundred ninety patients were randomly assigned (FAS): 243 to tiragolumab arm and 247 to control arm. At the cutoff date (February 6, 2022; median duration of follow-up, 14.3 months [PAS] and 13.9 months [FAS]), final analysis of PFS in the PAS (n = 397) did not reach statistical significance (stratified hazard ratio [HR], 1.11; P = .3504; median, 5.4 months tiragolumab v 5.6 months control). At the cutoff date (September 6, 2022; median duration of follow-up, 21.2 months [FAS]), median OS in the PAS at final OS analysis was 13.1 months in both arms (stratified HR, 1.14; P = .2859). Median PFS and OS in the FAS were consistent with the PAS. The proportion of patients with immune-mediated adverse events (AEs) in the tiragolumab and control arms was 54.4% and 49.2%, respectively (grade 3/4: 7.9% and 7.7%). AEs leading to treatment withdrawal occurred in 8.4% and 9.3% of tiragolumab- and control-treated patients, respectively.

Conclusion: Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

Trial registration: ClinicalTrials.gov NCT04256421.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Brain Neoplasms / drug therapy
  • Etoposide
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Small Cell Lung Carcinoma* / drug therapy

Substances

  • Antibodies, Monoclonal
  • atezolizumab
  • Etoposide

Associated data

  • ClinicalTrials.gov/NCT04256421