medwireNews: Adding atezolizumab to bevacizumab plus chemotherapy significantly delays disease progression and death among chemotherapy-naïve patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC), phase III study data show.
And the benefits of atezolizumab occurred irrespective of PD-L1 expression and EGFR or ALK mutation status, the IMpower150 study investigators report in The New England Journal of Medicine.
The intention-to-treat study population included 400 patients who were randomly assigned to receive bevacizumab, carboplatin, and paclitaxel (BCP) and 400 who were additionally given atezolizumab (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both.
Of these 800 patients, 692 with wild-type (WT) EGFR or ALK genes were followed-up for survival for more than 15 months. Patients with EGFR or ALK mutations were excluded from the primary analysis because they were not expected to derive additional benefit over chemotherapy from PD-L1 inhibitors such as atezolizumab.
During the follow-up period, 74.7% of the WT patients developed disease progression or died.
The risk for this combined outcome was a significant 38% lower among patients who received ABCP than among those who received BCP, with median progression-free survival (PFS) of 8.3 and 6.8 months, respectively.
The corresponding values among 445 WT patients who had high tumor expression of an effector T-cell (Teff) gene signature, defined as the expression of PD-L1, CXCL9, and IFN-γ messenger RNA, were 11.3 months and 6.8 months, equating to a 49% risk reduction with ABCP.
Secondary analyses showed that PFS was also significantly longer with ABCP than with BCP in the entire intention-to-treat population (including those with EGFR or ALK mutations) and among patients with low or negative PD-L1 expression, those with low Teff gene-signature expression, and those with liver metastases.
An interim survival analysis, after a median 20 months of follow-up, showed that median overall survival among the patients in the WT population was significantly longer with ABCP than with BCP, at 19.2 months versus 14.7 months, which corresponded to a 22% reduced risk for death with ABCP.
Martin Reck (German Center of Lung Research, Grosshansdorf) and team also note that “[t]he safety profile of ABCP was consistent with previously reported safety risks of the individual medicines.”
Treatment-related serious adverse events occurred in 25.4% of the patients in the ABCP group and in 19.3% of those in the BCP group, with 11 (2.8%) and nine (2.3%) treatment-related deaths reported, respectively
The trial findings were simultaneously reported at the ASCO Annual Meeting 2018, held in Chicago, Illinois, USA.
By Laura Cowen
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