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

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.

FIG 1.

CONSORT diagram. ^aIncludes two patients who screen-failed, rescreened, and later enrolled. ^bEntered in error. CE, carboplatin plus etoposide.

FIG 2.

PFS in (A) the primary analysis set and (B) the full analysis set. Clinical cutoff date: February 6, 2022. CE, carboplatin plus etoposide; HR, hazard ratio; NE, not evaluable; PFS, progression-free survival. ^aStratification factors are Eastern Cooperative Oncology Group and lactate dehydrogenase. ^bStatistical boundary: 0.001.

FIG 3.

OS in (A) the primary analysis set and (B) the full analysis set. Clinical cutoff date: September 6, 2022. CE, carboplatin plus etoposide; HR, hazard ratio; NE, not evaluable; OS, overall survival.

FIG 4.

Overall survival in key patient subgroups in (A) PAS, (B) PAS BEP, (C) FAS, and (D) FAS BEP. Clinical cutoff date: September 6, 2022. BEP, biomarker-evaluable; CE, carboplatin plus etoposide; ECOG, Eastern Cooperative Oncology Group; eCRF, electronic case report form; FAS, full analysis set; HR, hazard ratio; IC, immune cell score; LDH, lactate dehydrogenase; NE, not evaluable; PAS, primary analysis set; TC, tumor cell; ULN, upper limit of normal.