TOPLINE

Consolidation therapy with tiragolumab plus atezolizumab did not improve progression-free survival (PFS) or overall survival compared with durvalumab in patients with locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation. 

METHODOLOGY

• Concurrent platinum-based chemoradiation followed by consolidation durvalumab is the standard approach for unresectable, stage III NSCLC without progression after chemoradiation, but many patients ultimately experience disease recurrence, prompting efforts to improve outcomes by targeting other immune pathways such as TIGIT.
• The phase III SKYSCRAPER-03 study was designed to evaluate whether consolidation therapy with the TIGIT inhibitor tiragolumab plus atezolizumab improved clinical outcomes compared with durvalumab monotherapy in this patient population. 
• The open-label, multicenter study randomized 829 patients with newly diagnosed, locally advanced, unresectable, stage III NSCLC who did not progress after concurrent platinum-based chemoradiotherapy to receive either tiragolumab plus atezolizumab or durvalumab.
• Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 vs 1), programmed death-ligand 1 (PD-L1) status (tumor cells < 1% vs ≥ 1%), staging (IIIA vs IIIB or IIIC), and histology (nonsquamous vs squamous).
• The primary endpoint was PFS in patients with PD-L1-positive NSCLC (tumor cells ≥ 1%); secondary endpoints included overall survival and safety. The PD-L1-positive analysis included 419 patients (209 in the tiragolumab plus atezolizumab arm and 210 in the durvalumab arm); the PD-L1 all-comers population included 829 patients (413 and 416 in each arm, respectively).

TAKEAWAY

• At a median follow-up of 33.0 months in the PD-L1-positive population, tiragolumab plus atezolizumab did not significantly improve PFS compared with durvalumab monotherapy — median PFS of 19.4 vs 16.6 months (stratified hazard ratio [HR], 0.96; P = .76).
• The combination therapy did not significantly improve PFS in the PD-L1 all-comers population — median PFS of 14.2 months with tiragolumab plus atezolizumab vs 13.8 months with durvalumab (stratified HR, 1.00; 95% CI, 0.84-1.19).
• The combination therapy also did not significantly improve overall survival in either population. Median overall survival in the PD-L1-positive population was not estimable with tiragolumab plus atezolizumab compared with 54.8 months with durvalumab (stratified HR, 0.99; 95% CI, 0.73-1.34); in the PD-L1 all-comers population, median overall survival was 45.6 vs 45.8 months, respectively (stratified HR, 0.98; 95% CI, 0.80-1.20).
• The rate of adverse events was similar in both groups, occurring in 97.5% of patients who received tiragolumab plus atezolizumab and 97.3% of patients who received durvalumab. However, immune-mediated and treatment-related adverse events were more frequent with the combination: immune-mediated adverse events occurred in 76.4% vs 62.2%, respectively, and treatment-related adverse events occurred in 80.3% vs 67.1%.

IN PRACTICE

“The phase III SKYSCRAPER-03 study demonstrated that tiragolumab plus atezolizumab did not offer additional benefit over durvalumab alone in patients with locally advanced, unresectable, stage III NSCLC who had not progressed after concurrent platinum-based chemoradiation,” the authors of the study wrote.

SOURCE

The study, led by Heather A. Wakelee, MD, Stanford Cancer Institute/Stanford University School of Medicine in Stanford, California, and Rafał Dziadziuszko, MD, Medical University of Gdańsk in Gdańsk, Poland, was published online in Annals of Oncology.

LIMITATIONS

The open-label design may have introduced bias, although blinding was impractical because of differences in treatment administration. The lack of established predictive biomarkers for TIGIT inhibition also makes it difficult to identify patients who might benefit from the combination.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.