Tiragolumab and Atezolizumab Plus Chemotherapy Fails to Improve Survival Outcomes in Extensive-Stage SCLC

Charles M. Rudin, MD, PhD

Tiragolumab combined with atezolizumab (Tecentriq) plus carboplatin and etoposide (CE) demonstrated no additional survival benefits compared with atezolizumab plus chemotherapy alone in patients with treatment-naïve, extensive-stage small cell lung cancer (ES-SCLC), according to findings from the phase 3 SKYSCRAPER-02 trial (NCT04256421) presented at the 2022 ASCO Annual Meeting.¹

At a median of follow-up of 14.3 months for patients in the primary analysis set—which excluded patients with present or history of brain metastases—the median progression-free survival (PFS) was 5.4 months (95% CI, 5.7-4.5) with tiragolumab/stezolizumab/CE compared with 5.6 months (95% CI, 5.4-5.9) with atezolizumab/chemotherapy (HR, 1.1; 95% CI, 0.89-1.38; P = .3504). The treatment did not cross the statistical boundary of significance.

Similarly, the median overall survival (OS) among patients in the primary analysis set was 13.6 months (95% CI, 10.8-14.9) and 13.6 months (95% CI, 12.3-15.2), respectively, with no separation of the Kaplan-Meier curves (HR, 1.04; 95% CI, 0.79-1.36; P = .7963).

“The vast majority of patients with ES-SCLC continue to suffer disease progression, with a median of [approximately] 5.5 months from the time of diagnosis [to progression]. There’s clearly a major unmet need for the treatment of these patients,” Charles M. Rudin, MD, PhD, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, said in a presentation of the data.

“[There] doesn’t appear to be any subgroup that selectively benefits from the addition of tiragolumab,” Rudin said. “All of the confidence intervals overlap.”

Patients enrolled in SKYSCRAPER-02 were randomly assigned to receive tiragolumab (600 mg intravenously [IV] once every 3 weeks), atezolizumab (1200 mg IV once every 3 weeks), and CE (n = 243) or placebo plus atezolizumab and CE (n = 247). Coprimary end points were OS and investigator-assessed PFS in the primary analysis set.

Rudin noted that brain metastases were present among approximately 19% of patients in both arms at diagnosis and that approximately two-thirds were untreated.

A secondary end point was outcomes in all patients, including those with brain metastasis (full analysis set). The median PFS was 5.1 months (95% CI, 4.4-5.4) with the addition of trigolumab vs 5.4 months (95% CI, 4.5-5.7) with atezolizumab plus CE alone (HR, 1.08; 95% CI, 0.89-1.31). The median OS was 13.1 months (95% CI, 10.9-14.4) vs 12.9 months (95% CI, 12.1-14.5), respectively (HR, 1.02; 95% CI, 0.80-1.30).

Further, investigators analyzed the efficacy of trigolumab plus atezolizumab and CE among patients with brain metastases. In the experimental arm 47 patients had brain metastases compared with 46 in the control arm. The median OS was 11.7 months (95% CI, 8.21-not estimable [NE]) with trigolumab vs 10.4 months (95% CI, 9.03-NE) with placebo (HR, 0.92; 95% CI, 0.53-1.59).

“Response rates were higher with tiragolumab, but not meaningfully so [and are] what we expect for response rates for small cell lung cancer in the first-line setting,” Rudin said. Specifically, the objective response rate was 70.8% (95% CI, 64.6%-76.3%) for patients who received the investigative combination vs 65.6% (95% CI, 59.3%-71.4%) with atezolizumab plus CE alone. The median durations of response were 4.2 months (range, 4.1-4.4) and 5.1 months (4.4-5.8), respectively.

In terms of safety, investigators reported that the addition of tiragolumab was well tolerated and consistent with previously reported outcomes. Grade 3 or 4 treatment-related adverse effects (TRAEs) occurred in 52.3% of patients in the tiragolumab arm and 55.7% in the placebo arm. Grade 3 TRAEs occurred in 0.4% of the tiragolumab arm and 2.0% in the placebo arm.

Five percent of patients treated with the tiragolumab-containing arm had TRAEs that led to treatment discontinuation, compared with 5.3% in the placebo arm.

“We saw what we expected to see in terms of toxicity of the chemotherapy backbone and atezolizumab, [and there’s] not much difference in terms of safety signals between the 2 arms,” Rudin said.

Ultimately, the lack of benefit seen with the addition of tiragolumab on the SKYSCRAPER-02 trial mimic results previously seen on the EMPOWER-3 trial (NCT03409614), according to Rudin.

“From a clinical standpoint, based on these data, our conclusion is that targeting TIGIT in ES-SCLC does not appear to be therapeutically relevant,” Rudin said. “We’re continuing to follow these folks and biomarker analyses will be forthcoming. Those will be interesting in informing us about the subgroups that benefits from immunotherapy.”

Reference

Rudin CM, Liu SV, Lu S, et. al. SKYSCRAPER-02: primary results of a phase III, randomized, double-blind, placebo controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol. 2022;40(suppl 17):LBA8507. doi:10.1200/JCO.2022.40.17_suppl.LBA8507