IMpower133 Study Met Co-primary Endpoints at First Interim Analysis

Atezolizumab plus chemotherapy combination show improvement in progression-free and overall survival in the initial treatment of extensive-stage small cell lung cancer

On 25 June 2018, Roche announced that the phase III IMpower133 study met its co-primary endpoints of progression-free survival (PFS) and overall survival (OS) at its first interim analysis. The study demonstrated that first-line treatment with the combination of atezolizumab (TECENTRIQ) plus chemotherapy consisting of carboplatin and etoposide extended PFS and OS in patients with extensive-stage small-cell lung cancer (ES-SCLC). Safety for the atezolizumab and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. These data will be presented at an upcoming medical meeting. 

IMpower133 is the first phase III study with an immunotherapy-based combination to show improvement in PFS and OS in the initial treatment of ES-SCLC. There has been limited treatment progress for patients with ES-SCLC in the past 20 years. Data will be submitted to health authorities globally, including the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The results from the IMpower133 study add to the growing body of evidence demonstrating that atezolizumab-based combinations may be an effective treatment for different types of advanced lung cancer. This is the fourth positive phase III lung cancer study evaluating atezolizumab-based combination to read out this year and the fifth positive study overall. Currently, Roche has eight phase III lung cancer studies underway evaluating atezolizumab alone or in combination with other medicines across different types of lung cancer. 

IMpower133 is a phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of atezolizumab in combination with carboplatin and etoposide versus chemotherapy (carboplatin plus etoposide) alone in chemotherapy-naive patients with ES-SCLC. The study enrolled 403 patients who were randomised 1:1 to receive atezolizumab in combination with carboplatin and etoposide (arm A), or placebo in combination with carboplatin and etoposide (arm B, control arm).

During the treatment-induction phase, patients received treatment on 21-day cycles for four cycles, followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed. 

The co-primary endpoints were PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population and OS in the ITT population. The IMpower133 met its OS and PFS co-primary endpoints as per the study protocol. 

Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. Atezolizumab has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. 

Atezolizumab is already approved in the European Union, United States and more than 70 countries for patients with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma.

25 September 2018: IMpower133 study results presented at World Conference on Lung Cancer

The study team has presented the findings at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer in Toronto, Ontario, Canada, with a simultaneous publication on 25 September in The New England Journal of Medicine.

A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (HR for death, 0.70; p = 0.007). The median PFS was 5.2 months and 4.3 months (HR for disease progression or death, 0.77; p = 0.02).

The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings reported.

The authors concluded that addition of atezolizumab to chemotherapy in the first-line treatment of ES-SCLC resulted in significantly longer OS and PFS than chemotherapy alone. 

Reference

Horn L, Mansfield AS, SzczęsnaA, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. NEJM; Published online 25September, 2018. DOI: 10.1056/NEJMoa1809064