KEY TAKEAWAYS
- The IMpower133 phase 1/3 trial (NCT02763579) aimed to evaluate the OS and PFS of patients with untreated ES-SCLC who received atezolizumab plus CP/ET followed by maintenance atezolizumab compared to placebo plus CP/ET followed by maintenance placebo.
- Patients in the study were randomly assigned to receive four 21-day cycles of CP/ET with atezolizumab or a placebo, followed by atezolizumab or a placebo for maintenance.
- The study outcomes demonstrated that even after controlling for baseline variables, the atezolizumab-induced beneficial treatment impact persisted.
The phase 1/3 IMpower133 study demonstrated that atezolizumab plus carboplatin and etoposide (CP/ET) followed by maintenance atezolizumab improved overall survival (OS) and progression-free survival (PFS) compared to placebo plus CP/ET followed by maintenance placebo in patients with extensive-stage SCLC (ES-SCLC). We examined the benefits of atezolizumab versus placebo in patients who received maintenance therapy and evaluated the safety profile of maintenance therapy.
In the study, patients with untreated ES-SCLC were randomly randomized to receive either a placebo or atezolizumab for four consecutive 21-day cycles of CP/ET, then either atezolizumab or a placebo for maintenance. OS and investigator-assessed PFS served as the primary outcomes. A multivariate Cox model was employed to assess the treatment effect and consider lead-time bias from the beginning of maintenance treatment. A generalized linear model identified prognostic or predictive factors for reaching the maintenance phase. In both treatment arms, a comparable percentage of patients received at least one maintenance therapy dose (atezolizumab: 77%, n = 154 of 201; placebo: 81%, n = 164 of 202), and these patients were included in the maintenance analysis population. The Eastern Cooperative Oncology Group performance status of 0 and the absence of liver metastases at baseline were identified as prognostic factors for entering the maintenance phase. The positive effect of atezolizumab treatment persisted after adjusting for baseline characteristics. Median OS and progression-free survival PFS from the start of maintenance therapy were 12.5 versus 8.4 months (hazard ratio = 0.59, 95% confidence interval: 0.43-0.80) and 2.6 versus 1.8 months (hazard ratio = 0.63 [95% confidence interval: 0.49-0.80]), respectively, in the atezolizumab versus placebo arm. Treatment-related adverse events occurred in 41% (n = 64 of 155) and 25% (n = 41 of 163) of safety-evaluable patients in the atezolizumab and placebo arms, respectively, from the start of maintenance therapy. Of these adverse events, 28% (n = 43 of 155) and 23% (n = 37 of 163) were grade 3 or 4; one patient in the placebo arm and no patients in the atezolizumab arm had a grade 5 treatment-related adverse event. These findings, combined with other trials investigating immunotherapy in ES-SCLC, suggested that induction with atezolizumab plus CP/ET and maintenance therapy with atezolizumab are crucial components contributing to the observed OS benefit in IMpower133. Despite continuing atezolizumab treatment during the maintenance phase, safety results were similar between the treatment arms during randomization and the start of maintenance therapy.
Source: https://pubmed.ncbi.nlm.nih.gov/35764236/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02763579/
Reck M, Mok TSK, Mansfield A, De Boer R, Losonczy G, Sugawara S, Dziadziuszko R, Krzakowski M, Smolin A, Hochmair M, Garassino MC, de Castro Junior G, Bischoff H, Lam S, Cardona A, Morris S, Liu SV. Brief Report: Exploratory Analysis of Maintenance Therapy in Patients With Extensive-Stage SCLC Treated First Line With Atezolizumab Plus Carboplatin and Etoposide. J Thorac Oncol. 2022 Sep;17(9):1122-1129. doi: 10.1016/j.jtho.2022.05.016. Epub 2022 Jun 25. PMID: 35764236.
