Atezolizumab Combination Confirmed as First-Line Standard in Advanced Small Cell Lung Cancer: Presented at ESMO Congress

By Jenny Powers

BARCELONA, Spain -- October 3, 2019 -- More patients with extensive-stage small cell lung cancer (SCLC) treated with atezolizumab in addition standard carboplatin plus etoposide live longer than similar patients receiving standard chemotherapy alone, according to a study presented here at the 2019 Annual Congress of the European Society of Medical Oncology (ESMO).

“IMpower133 is the first trial to demonstrate a significant improvement in survival as first-line treatment for patients with SCLC since the introduction of platinum-based chemotherapy in the 1990s,” said Martin Reck, MD, Lung Clinic, Grosshansdorf, Germany.

IMpower133 included 403 treatment-naive patients with advanced SCLC who were randomised to carboplatin plus etoposide plus either atezolizumab (n = 201) or placebo (n = 202) for four 21-day cycles followed by maintenance therapy with atezolizumab or placebo, according to the prior treatment. Treatment continued until progressive disease or loss of clinical benefit. Patients with treated asymptomatic brain metastases were eligible, and programmed death-ligand 1 (PD-L1) testing was not required, although samples were obtained where possible.

After a median follow-up time of 22.9 months, median overall survival (OS) remained consistent with the primary analysis at 12.3 months in patients receiving atezolizumab plus chemotherapy and 10.3 months in patients receiving chemotherapy alone (hazard ratio = 0.76; P = .0154).

At 6, 12, and 18 months, respectively, 86%, 52%, and 34% of patients receiving atezolizumab plus chemotherapy were alive, compared with 83%, 39%, and 21% of patients receiving standard chemotherapy plus placebo.

The primary data analysis provided the basis for approval of atezolizumab as first-line treatment for advanced SCLC by the U.S. Food and Drug Administration in March 2019 and the European Medicines Agency in September 2019.

“At the time of this analysis, 9.1% of patients in the atezolizumab combination arm had an ongoing response versus 2.3% in the chemotherapy arm,” said Dr. Reck.

A consistent benefit with the addition of atezolizumab was observed across subgroups based on patient characteristics. Interestingly, patients aged ≥65 years had an increased survival benefit with atezolizumab compared with patients aged

“A slight difference with regard to age was observed, which needs further exploration,” noted Dr. Reck.

“Exploratory biomarker analyses that included both PD-L1 immunohistochemistry and blood-based tumour mutational burden suggest that patients derive treatment benefit from the addition of atezolizumab regardless of biomarker status,” he added.

A post hoc exploratory analysis was conducted for OS by PD-L1 expression in 137 (34%) patients in the intent-to-treat population with PD-L1 expression status (Ventana SP263 assay).

“PD-L1 expression was seen mostly on the immune cells, with only limited expression on the tumour cells,” said Dr. Reck.

Tumour cells were negative for PD-L1 expression in 94.2% of the biomarker-evaluable population, compared with 49.6% of immune cells. Only 1.5% and 20.4% of patients had high (≥5%) PD-L1 expression on immune cells and tumour cells, respectively.

“There was no correlation between PD-L1 expression status and the efficacy of the combination with atezolizumab,” said Dr. Reck.

Subsequent therapy was required by 54.7% of patients receiving the atezolizumab combination versus 61.9% of patients receiving placebo plus chemotherapy.

As expected, more immune-related adverse events (AEs) occurred in the atezolizumab arm than in the chemotherapy only arm (41.4% vs 24.5%). The most frequent immune-related AEs with atezolizumab were rash (20.2%), hepatitis (7.6%), changes in thyroid function (18.2%), and infusion-related reactions (5.5%). There were no grade 5 immune-related AEs.

“These findings further support the addition of atezolizumab to carboplatin plus etoposide as the standard of care in patients with extensive-stage small-cell lung cancer,” concluded Dr. Reck.

Funding for the study was provided by F. Hoffmann-La Roche.
[Presentation title: IMpower133: Updated Overall Survival (OS) Analysis of First-Line (1L) Atezolizumab (Atezo) + Carboplatin + Etoposide in Extensive-Stage SCLC (ES-SCLC) (ID 2374). Abstract 1736O]

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