Patients with extensive-stage small-cell lung cancer (ES-SCLC) are currently treated with a combination of an immune checkpoint inhibitor and carboplatin-etoposide. However, most patients experience disease progression on this regimen, resulting in a median survival of approximately 12 months. In an effort to address this medical need, the phase 3 SKYSCRAPER-02 trial introduced tiragolumab into the regimen. Unfortunately, the addition of tiragolumab to atezolizumab plus carboplatin and etoposide did not lead to an improved OS in patients with ES-SCLC.
Current first-line treatment options for extensive-stage small-cell lung cancer (ES-SCLC) include the combinations of atezolizumab plus carboplatin and etoposide (CE) or durvalumab plus chemotherapy. Although these regimens improve the outcome of ES-SCLC patients, most of them will experience disease progression, resulting in a median OS of approximately 12 months. As such, there is a significant unmet need for new therapeutic options able to improve long-term outcomes in ES-SCLC patients. The T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a novel inhibitory immune checkpoint receptor with high expression on various immune cell types implicated in multiple cancers, including SCLC, thereby positioning it as a promising therapeutic target for this particular cancer.
Inspired by these promising findings, the phase III SKYSCRAPER-02 study aimed to investigate whether the benefits derived from atezolizumab plus CE could be further enhanced by the adding the TIGIT antibody tiragolumab to the treatment regimen in treatment-naïve ES-SCLC. This article presents the final results of progression-free survival (PFS) and overall survival (OS).
The phase 3 SKYSCRAPER-02 trial included adult patients with treatment-naïve ES-SCLC enrolled across 121 sites in 23 countries. In total, 490 patients were randomly assigned to receive atezolizumab and CE with tiragolumab 600 mg (n=243) or placebo (n=247), followed by maintenance with atezolizumab plus tiragolumab or placebo, respectively. The primary endpoints included PFS and OS in patients without a history/presence of brain metastases. Additional endpoints included PFS and OS in all patients regardless of brain metastases status.
After a median follow-up of around 14 months, this trial failed to meet its primary endpoint, as PFS was not significantly improved with tiragolumab over placebo in patients without history/presence of brain metastases (HR[95%CI]: 1.11[0.89-1.38]; p = 0.3504). The median PFS was reported at 5.4 vs. 5.6 in the tiragolumab and control arms, respectively. Similarly, the addition of tiragolumab did not prolong the OS, with a median OS of 13.1 months in both arms (HR[95%CI]:1.14[0.90-1.44]; p= 0.2859). Comparable outcomes were also observed in the overall study population, without a significant difference between the arms in PFS or OS. Immune-mediated adverse events (AEs) were observed in 54.4% vs. 49.2% of patients in the tiragolumab and control arms, respectively, with grade 3/4 events occurring in 7.9% vs. 7.7% of patients. AEs leading to treatment withdrawal occurred in 8.4% and 9.3% of patients in the tiragolumab and control arms, respectively.
In conclusion, adding tiragolumab to atezolizumab and CE does not improve outcomes in patients with treatment-naïve ES-SCLC. The combination did demonstrate a good tolerability without any new safety concerns.
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