Atezolizumab added to carboplatin and etoposide continues to demonstrate an improved overall survival benefit for patients with extensive-stage small-cell lung cancer (ES-SCLC), updated results from the IMpower133 trial shows.

Presenting the latest findings to ESMO 2019 congress, Dr. Martin Reck from Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany said there was a high unmet medical need for first-line treatment of ES-SCLC.

“IMPower133 is one of the first trials showing a benefit for systemic treatment and first-line therapy for patients with extensive small cell lung cancer,” he told delegates.

Earlier results had demonstrated significant improvement in efficacy and tolerable safety with the addition of atezolizumab to chemotherapy (carboplatin and etoposide) and yielded statistically significant improvement in the ITT population with a median OS of 12.3 months (HR: 0.70; 95% CI: 0.54, 0.91; p = 0.007) and a median PFS of 5.2 months (HR: 0.77; 95% CI: 0.62, 0.96; p = 0.02)

“Following this data, atezolizumab plus carboplatin and etoposide was approved for first line treatment of ES-SCLC by the FDA in March 2019 and by the EMA in September 2019,” he said.

“Today we will show you updated survival analyses with a longer follow-up of 9 months and additional analyses on translational investigations and safety reporting,” he explained.

The study included 403 patients who were randomised to atezolizumab plus carboplatin and etoposide (CP/ET) or CP/ET plus placebo for four 21-day cycles followed by atezolizumab or placebo as maintenance therapy until progression of disease or loss of clinical benefit. Stratification was performed according to gender, performance status and the presence of brain metastases.

The updated OS in the ITT population showed that at a median follow up of 22.3 months, the median overall survival (OS) was 12.3 months in patients randomised to atezolizumab plus CP/ET and 10.3 months in patients who received placebo plus CP/ET (HR 0.76; CI 0.60-0.95; P=0.0154).

At the 18 month landmark 34% of patients were alive in the atezolizumab group compared to 21% in the placebo plus CP/ET group.

Response rates were similar between the arms with 60.2% in the atezolizumab and CP/ET arm having a complete or partial response compared to 64.4% in CP/ET alone arm.

The median duration of response was also similar between both arms at 4.2 and 3.9 months, respectively.

“At the time of the present analysis 9 percent of patients in the atezolizumab combination arm (n=11) had an ongoing response compared to 2.3% in the chemotherapy alone arm (n=3),” Dr Reck noted.

An exploratory biomarker analysis that included both PD-L1 IHC and bTMB suggested that patients derived treatment benefit from the addition of atezolizumab regardless of their biomarker status, Dr Reck told delegates.

He noted that older patients seemed to have a more pronounced survival benefit with atezolizumab compared to younger patients but this finding needed further exploration ( ≥65 years median OS 14.4 months vs 12.1 months for < 65 years)

“With longer follow up we do see a consistent benefit for survival favouring the combination of atezolizumab and chemotherapy compared to chemotherapy alone… overall, these results confirm that atezolizumab with platinum-based chemotherapy as an attractive new therapeutic opportunity for patients with advanced small cell lung cancer,” he concluded.