medwireNews: First-line treatment with the checkpoint inhibitor atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer (SCLC) significantly extends overall survival (OS) and progression-free survival (PFS) versus chemotherapy alone, indicates the phase III IMpower133 trial.
The risk for death was reduced by 30% in 201 treatment-naïve patients who received the combination of atezolizumab plus carboplatin and etoposide, at a median OS of 12.3 months compared with 10.3 months for 202 patients who received chemotherapy plus placebo. The 1-year OS rate was 51.7% and 38.2%, respectively, a difference of approximately 13 percentage points.
These findings suggest that “combining checkpoint inhibition with cytotoxic therapy during induction may be beneficial and potentially necessary to improve [OS] beyond that seen with the current standard of care, and thus it may be a preferred treatment approach over maintenance checkpoint-inhibitor therapy alone,” write Leora Horn (Vanderbilt University Medical Center, Nashville, Tennessee, USA) and her co-researchers in The New England Journal of Medicine.
PFS was also significantly extended with the addition of atezolizumab, with a 23% lower risk for disease progression or death, and a median duration of 5.2 months versus 4.3 months with chemotherapy alone.
“Benefits with respect to [OS] and [PFS] were consistent across patient subgroups,” say the researchers. And although objective response rates and median duration of response were similar in the two groups, more patients given atezolizumab (14.9 vs 5.4%) had an ongoing response at the time of data cutoff.
The study authors note that in contrast with previous results suggesting “an association between high tumor mutational burden and better clinical outcomes in patients receiving cancer immunotherapies,” the current study found no such association, potentially as a result of the highly active and myelosuppressive nature of the platinum and etoposide combination.
There were no major differences in the safety profile between study arms, with adverse events of grade 3 or worse experienced by 58.1% of patients in the atezolizumab group and 57.6% in the placebo group, and no new safety signals were observed.
In conclusion, Horn et al summarize that “this multinational trial in the first-line treatment of extensive-stage small-cell lung cancer in a patient population typical for this disease showed that the addition of atezolizumab to carboplatin and etoposide was associated with significantly longer [OS] and [PFS].”
These results were simultaneously presented at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer in Toronto, Ontario, Canada.
By Catherine Booth
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