Atezolizumab–chemotherapy combination boosts extensive-stage SCLC survival
medwireNews: The addition of atezolizumab to chemotherapy has significantly improved both the overall survival (OS) and progression-free survival (PFS) of treatment naïve-patients with extensive-stage small-cell lung cancer (SCLC), results from the IMpower133 trial indicate.
After a median follow-up of 13.9 months, the median OS was 12.3 months for the 201 patients who were randomly assigned to receive an induction regimen of four 21-day cycles of carboplatin plus etoposide with atezolizumab 1200 mg on day 1, followed by maintenance atezolizumab until unacceptable toxicity or disease progression.
This compared with a median OS of 10.3 months for the 202 patients who were assigned to receive placebo instead of atezolizumab, giving a significant hazard ratio for death of 0.70 in favour of treatment with the PD-L1 inhibitor.
Median PFS was also significantly better with atezolizumab than placebo, at 5.2 versus 4.3 months, and the HR for disease progression or death was 0.77, say Leora Horn, from Vanderbilt University Medical Center in Nashville, Tennessee, USA, and co-investigators.
The team notes that these atezolizumab survival benefits were “consistent across key subgroups”, including those with blood-based tumour mutation burden levels at either a cutoff of 10 or 16 mutations/megabase, whereas earlier studies suggested that perhaps patients with higher mutational burden may have greater clinical benefit.
However, there was no significant difference in the treatment arms for OS among patients with brain metastases. “Owing to the small number of patients with brain metastases enrolled in the trial and the exploratory nature of the analysis, no conclusions can be drawn”, the researchers comment.
They also highlight “an imbalance in OS benefit” among patients younger and older than 65 years in favour of older individuals. “There is no simple biologic explanation for this observation, and further analyses are needed to understand whether other factors may have contributed to this result”, Horn et al remark.
The objective response rate was similar between the atezolizumab and control groups (60.2 vs 64.4%), as was the rate of complete response (2.5 vs 1.0%) and partial response (57.7 vs 63.4%). But while the median duration of response was comparable (4.2 vs 3.9 months), atezolizumab-treated patients were more likely to have an ongoing response at data cutoff than their placebo-treated counterparts (14.9 vs 5.4%).
The investigators say the safety profile of atezolizumab was “consistent” with that in earlier reports, with grade 3 or 4 adverse events occurring in 56.6% of patients versus 56.1% of controls. The most common side effects at this severity were neutropenia (22.7 vs 24.5%), anaemia (14.1 vs 12.2%) and decreased neutrophil count (14.1 vs 16.8%).
The IMpower133 trial results were reported at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer in Toronto, Ontario, Canada, and simultaneously published in The New England Journal of Medicine.
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