Tiragolumab Combo Does Not Improve Outcomes in Untreated ES-SCLC

“Although tiragolumab did not add additional benefit to atezolizumab plus chemotherapy, the control arm further confirmed the combination of atezolizumab and chemotherapy as [standard of care] for ES-SCLC," according to the authors of the phase 3 SKYSCRAPER-02 trial (NCT04256421).

Adding tiragolumab to atezolizumab (Tecentriq) and chemotherapy did not produce improvements in clinical outcomes among patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC) compared with atezolizumab plus chemotherapy alone, according to findings from the phase 3 SKYSCRAPER-02 trial (NCT04256421) published in Journal of Clinical Oncology.

The median progression-free survival (PFS) across the full analysis set (FAS) was 5.4 months with the tiragolumab-based regimen vs 5.6 months with atezolizumab plus chemotherapy (HR, 1.11; 95% CI, 0.89-1.38; P = .3504). Among those included in the primary analysis set (PAS), the median PFS with each respective treatment was 5.1 months vs 5.4 months (HR, 1.08; 95% CI, 0.89-1.31). The PFS rates in each respective arm across the PAS were 35.2% vs 42.4% at 6 months and 14.2% vs 17.3% at 12 months; the corresponding rates in the FAS were 31.3% vs 38.0% and 12.3% vs 14.1%.

Investigators highlighted a median overall survival (OS) of 13.1 months in the atezolizumab arm vs 13.1 months in the control arm across the PAS (HR, 1.14; 95% CI, 0.90-1.44; P = .2859). Additionally, the median OS in each respective arm across the FAS was 12.8 months vs 12.9 months (HR, 1.09; 95% CI, 0.88-1.35; P = .4205). The 24-month OS rate in each respective arm was 20% vs 28% in the PAS as well as 21% vs 26% in the FAS.

Subgroup analyses indicated a median OS of 14.9 months with the tiragolumab regimen vs 19.4 months in the control arm in patients with lactate dehydrogenase levels at or below the upper limit of normal across the FAS (HR, 1.46; 95% CI, 1.02-2.10). Additionally, the median OS in each respective treatment arm was 11.7 months vs 10.8 months among patients with brain metastases at baseline in the FAS (HR, 0.93; 95% CI, 0.57-1.50; P = .7523). The median OS in each respective treatment arm was 14.5 months vs 13.1 months among those with PD-L1–positive tumors in the FAS (HR, 1.01; 95% CI, 0.75-1.37). Investigators stated that these subgroup findings should be interpreted with caution due to the small sample sizes.

“To our knowledge, this is the first randomized, placebo-controlled phase 3 study to show long-term data when combining an anti-TIGIT antibody with an anti–PD-L1 antibody for patients with untreated ES-SCLC,” the study authors wrote. “Although tiragolumab did not add additional benefit to atezolizumab plus chemotherapy, the control arm further confirmed the combination of atezolizumab and chemotherapy as [standard of care] for ES-SCLC.”

A total of 490 patients included in the FAS of the SKYSCRAPER-02 trial were randomly assigned 1:1 to receive 600 mg of intravenous tiragolumab (n = 243) or matched placebo (n = 247) on day 1 plus 1200 mg of intravenous atezolizumab on day 1, carboplatin at area under the curve 5 mg/mL per minute on day 1, and 1000 mg/m² of etoposide on days 1 to 3 for 21-day cycles.

The study’s primary end points were PFS and OS in all patients in the PAS, which included those without a history or presence of brain metastases at baseline. Secondary end points included confirmed objective response rate (ORR) and duration of response (DOR).

Patients 18 years and older with histologically or cytologically confirmed ES-SCLC who received no prior treatment were eligible for enrollment on the study. Having an ECOG performance status of 0 or 1 was another requirement for enrollment.

The median age was 65 years (range, 34-85) in the atezolizumab arm and 65 years (range, 33-83) in the placebo arm across the FAS. Additionally, most patients in each respective arm were male (66.7% vs 66.4%), White (71.2% vs 70.4%), and had an ECOG performance status of 1 (64.2% vs 66.8%). Investigators reported that 36.6% and 38.1% of patients in each group had liver metastases at baseline.

The confirmed ORR in the PAS was 73.5% in the tiragolumab arm, which included complete responses (CRs) in 1.5% and partial responses (PRs) in 71.9%. The ORR was 66.7% in the control arm, including CRs in 1.5% and PRs in 65.2%. Additionally, the median DOR in patients receiving the tiragolumab regimen and control regimen, respectively, was 4.2 months vs 5.6 months in the PAS.

At least 1 any-grade adverse effect (AE) affected 99.6% of patients in the tiragolumab arm and the 99.6% of those in the control arm. Grade 3 or higher toxicities occurred in 64.0% and 63.8% of patients in each respective group. Additionally, any-grade treatment-related AEs (TRAEs) were reported in 93.3% and 92.3% of patients from each respective arm, and high-grade TRAEs affected 52.7% and 55.7%.

Frequent any-grade TRAEs in the atezolizumab and control arms, respectively, included anemia (36.0% vs 37.8%), neutropenia (25.9% vs 30.1%), alopecia (24.3% vs 25.2%), and pruritus (24.3% vs 10.2%). Investigators highlighted 3 fatal AEs of special interest, which included 1 instance of hepatorenal syndrome in the tiragolumab arm and 2 interstitial lung disease events in the control arm.

Reference

Rudin CM, Liu SV, Soo RA, et al. SKYSCRAPER-02: tiragolumab in combination with atezolizumab plus chemotherapy in untreated extensive-stage small-cell lung cancer. J Clin Oncol. Published online November 17, 2023. doi:10.1200/JCO.23.01363