Atezolizumab Combo Real-World Data Match Clinical Trial Efficacy in SCLC

Real-world atezolizumab plus chemotherapy data demonstrated similar efficacy compared with what the phase 3 IMpower133 trial showed.

Atezolizumab (Tecentriq) plus carboplatin and etoposide demonstrated clinical practice efficacy in patients with extensive-stage small cell lung cancer (ES-SCLC) that was consistent with the results seen in the phase 3 IMpower133 trial (NCT02763579), according to data from the observational J-TAIL-2 trial (NCT04501497) published in JTO Clinical and Research Reports.¹

In the overall efficacy population, the median overall survival (OS) was 16.5 months (95% CI, 14.9-18.2), and the 12-month OS rate was 63.7% (95% CI, 58.6%-68.3%); median progression-free survival (PFS) was 5.1 months (95% CI, 4.7-5.3), and the 12-month PFS rate was 13.9% (95% CI, 10.7%-17.6%). The overall response rate (ORR) was 66.1% (95% CI, 61.1%-70.9%) in the efficacy population with measurable lesions.

In the subgroup of patients dissimilar to those in the IMpower133 trial (n = 289) and the subgroup of patients similar to those in the IMpower133 trial (n = 110), the median OS was 15.5 months (95% CI, 12.6-17.8) vs 19.1 months (95% CI, 16.2-21.8; HR, 1.32; 95% CI, 0.98-1.77), and the 12-month OS rate was 58.5% (95% CI, 52.4%-64.1%) vs 77.5% (95% CI, 68.0%-84.4%). The median PFS was 4.8 months (95% CI, 4.6-5.3) vs 5.4 months (95% CI, 4.9-5.9; HR, 1.14; 95% CI, 0.90-1.45), and the 12-month PFS rate was 12.8% (95% CI, 9.2%-17.0%) vs 16.8% (95% CI, 10.5%-24.5%). The ORRs were 64.9% (95% CI, 58.9%-70.6%) and 69.1% (95% CI, 59.6%-77.6%), respectively.

“Results from J-TAIL-2 support the use of atezolizumab plus [carboplatin and etoposide] in patients with ES-SCLC in routine clinical practice,” Akihio Gemma, MD, PhD, president of Nippon Medical School in Tokyo, Japan, and fellow authors wrote in the paper.¹ “Subgroup analyses revealed an acceptable benefit/risk profile in patients who were ineligible for the IMpower133 trial. There were no new safety signals, and data suggest that the regimen may be suitable in patients with comorbidities based on a risk/benefit evaluation.”

A total of 403 patients were enrolled in the trial. Eligible patients were at least 20 years old and scheduled to start treatment consisting of atezolizumab plus carboplatin and etoposide for ES-SCLC. Drug dosage and schedules were based on local labels.

The median age was 71 years (range, 39-91), 80.1% were male, 60.8% were 70 years or older, and 95.8% were current or former smokers; in the intention-to-treat population, 16.6% had an ECOG performance status of 2 or higher, 26.8% had brain metastasis, and 6.9% had interstitial lung disease.

Patients were considered IMpower133-like if they met the eligibility criteria of the IMpower133 trial and were IMpower133-unlike if they would have been ineligible for the IMpower133 trial due to an ECOG performance status from 2 to 4, inadequate hematologic or end-organ function, brain metastases, history or complication of autoimmune disease, lack of target lesions, and double cancer, among other reasons.

The trial’s primary end point was the 12-month OS rate. Secondary end points included OS, PFS, ORR, and safety, among others.

Among patients with an ECOG performance status of 2 or higher (n = 66) vs less than 2 (n = 333), median OS was 11.1 months vs 17.9 months (HR, 2.00; 95% CI, 1.43-2.80), and median PFS was 4.2 months vs 5.2 months (HR, 1.44; 95% CI, 1.08-1.91). In patients who experienced an immune-related adverse event (AE) and those who didn’t, median OS was 21.5 months vs 15.3 months (HR, 0.64; 95% CI, 0.46-0.89), and median PFS was 6.5 months vs 4.8 months (HR, 0.57; 95% CI, 0.44-0.74).

AEs of any cause occurred in 85.5% of patients. Grade 3 or higher AEs were observed in 66.3% of patients; the most common were decreased neutrophil counts (38.5%), decreased white blood cell counts (12.5%), febrile neutropenia (8.3%), and decreased platelet counts (8.3%). Also, 2.8% of patients experienced grade 5 AEs; these were pneumonia (n = 3), aspiration pneumonia, bacterial pneumonia, interstitial lung disease, pneumonitis, febrile neutropenia, peripheral arterial occlusive disease, gastrointestinal hemorrhage, and death (n = 1 each). Immune-related AEs occurred in 23.5% of patients, and 7.8% were grade 3 or higher; 0.5% were grade 5 and included interstitial lung disease and pneumonitis.

The study authors noted that 72.7% of patients would have been ineligible for the IMpower133 trial, and that, though the IMpower133-like subgroup of the J-TAIL-2 trial was similar to the population of the IMpower133 trial, it was a distinct group.

Compared side-by-side, the IMpower133 trial and the J-TAIL-2 trial achieved a median OS of 12.3 months and 16.5 months, respectively; a 12-month OS rate of 51.7% and 63.7%; and a median PFS of 5.2 months and 5.1 months.² Ultimately, these results support the continued use of this regimen in patients with ES-SCLC.

References

1. Miyauchi E, Nishio M, Ohashi K, et al. J-TAIL-2: a prospective, observational study of atezolizumab combined with carboplatin and etoposide in patients with extensive-stage SCLC in Japan. JTO Clin Res Rep. 2025;6(3):100783. doi:10.1016/j.jtocrr.2024.100783
2. Liu SV, Reck M, Mansfield AS, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-630. doi:10.1200/JCO.20.01055