As reported in the Journal of Clinical Oncology by Charles M. Rudin, MD, PhD, and colleagues, the phase III SKYSCRAPER-02 trial showed no progression-free or overall survival benefit with the addition of the T-cell immunoglobulin and ITM domain (TIGIT) inhibitor tiragolumab to atezolizumab and chemotherapy in patients with previously untreated extensive-stage small cell lung cancer (SCLC).
Charles M. Rudin, MD, PhD
Study Details
The double-blind trial included 490 patients from sites in 23 countries. They were randomly assigned between February 2020 and March 2021 to receive intravenous tiragolumab at 600 mg on day 1 of four 21-day cycles (n = 243), or placebo (n = 247) plus atezolizumab at 1,200 mg on day 1; carboplatin at area under curve = 5 on day 1; and etoposide at 100 mg/m2 on days 1, 2, and 3 of each cycle. Patients then received maintenance tiragolumab or placebo plus atezolizumab in 21-day cycles until radiographic progression.
The primary endpoints of the study were investigator-assessed progression-free survival and overall survival in patients without a history/presence of brain metastases (primary analysis set). The primary analysis set consisted of 397 patients, including 196 in the tiragolumab group and 201 in the control group. The endpoints were also assessed in all patients (full analysis set).
Key Findings
At final analysis of progression-free survival, median follow-up was 14.3 months in the primary analysis set and 13.9 months in the full analysis set. In the primary analysis set, median progression-free survival was 5.4 months (95% confidence interval [CI] = 4.7–5.5 months) in the tiragolumab group vs 5.6 months (95% CI = 5.4–5.9 months) in the control group (hazard ratio [HR] = 1.11, 95% CI = 0.89–1.38, P = .3504). Rates at 6 and 12 months were 35.2% vs 42.4% and 14.2% vs 17.3%, respectively.
In the full analysis set, median progression-free survival was 5.1 months (95% CI = 4.4–5.4 months) in the tiragolumab group vs 5.4 months (95% CI = 4.5–5.7 months) in the control group (HR = 1.08, 95% CI = 0.89–1.31). Rates at 6 and 12 months were 31.3% vs 38.0% and 12.3% vs 14.1%, respectively.
At final analysis of overall survival, median follow-up was 21.2 months. In the primary analysis set, median overall survival was 13.11 months (95% CI = 10.84–14.39 months) in the tiragolumab group vs 13.14 months (95% CI = 12.16–15.11 months) in the control group (HR = 1.14, 95% CI = 0.90–1.44, P = .2859). Rates at 24 months were 20% vs 28%.
In the full analysis set, median overall survival was 12.75 months (95% CI = 10.84–14.29 months) in the tiragolumab group vs 12.91 months (95% CI = 11.99–14.52 months) in the control group (HR = 1.09, 95% CI = 0.88–1.35). Rates at 24 months were 21% vs 26%.
Overall, treatment-related grade 3 or 4 adverse events occurred in 52.7% of patients in the tiragolumab arm vs 55.7% of patients in the control arm; the most commonly reported events were anemia and neutropenia. Immune-mediated adverse events occurred in 54.4% vs 49.2%, and were grade 3 or 4 in 7.9% vs 7.7%. Adverse events led to treatment discontinuation in 8.4% vs 9.3% of patients.
The investigators concluded, “Tiragolumab did not provide additional benefit over atezolizumab and carboplatin/etoposide in untreated extensive-stage SCLC. The combination was well tolerated with no new safety signals.”
Dr. Rudin, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Genentech Inc. and F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.
