Atezolizumab Leads to Longer OS for Some Types of Advanced NSCLC, Study Says

Treatment with atezolizumab (Tecentriq) resulted in significantly longer overall survival (OS) than platinum-based chemotherapy among certain patients with metastatic non–small cell lung cancer (NSCLC) and high programmed-death ligand-1 (PD-L1) expression.

The improvement was seen regardless of histologic type, according to the phase 3 study, which was published in The New England Journal of Medicine. The trial, IMpower110, is a global, randomized, open-label trial designed to evaluate the efficacy and safety of atezolizumab as compared with platinum-based chemotherapy in PD-L1–selected patients with epidermal growth factor receptor (EGFR) or translocations of anaplastic lymphoma kinase (ALK) wild-type tumors.

Efficacy and safety of atezolizumab as first-line therapy for advanced NSCLC with high levels of PD-L1 expression is not known, the authors said, and additional treatment options are needed.

The patients were positive for PD-L1 as determined by the SP142 qualitative immunohistochemical assay on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells.

The researchers also conducted prespecified efficacy analyses by subgroups defined by blood-based tumor mutational burden.

Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. OS was tested according to PD-L1 expression status among patients in the intention-to-treat population; in a subgroup analysis, patients with EGFR and ALK wild-type tumors were also prospectively assessed for OS and progression-free survival (PFS).

The trial enrolled 572 patients; 285 were assigned to receive atezolizumab and 287 were assigned to receive chemotherapy. Patients were randomized from July 21, 2015 to February 20, 2018.

Participants with EGFR and ALK wild-type tumors numbered 554, with 277 patients in each group.

Eighteen patients with an EGFR mutation or ALK translocation were enrolled based on the original study protocol. The protocol was later amended to exclude these patients from the primary analysis after new information suggested that they may not benefit from immune-checkpoint inhibitor monotherapy. They were included in the safety population.

Atezolizumab (1200 mg intravenously) or chemotherapy (4 or 6 cycles) was administered once every 3 weeks. In the chemotherapy group, patients with nonsquamous NSCLC received either cisplatin or carboplatin in addition to pemetrexed intravenously; patients with squamous NSCLC received a regimen of cisplatin plus gemcitabine or a regimen of carboplatin plus gemcitabine.

In the subgroup of patients (n = 205) with EGFR and ALK wild-type tumors who had the highest expression of PD-L1, those on atezolizumab had median OS extended by 7.1 months compared with the chemotherapy group (20.2 months vs. 13.1 months; HR for death, 0.59; 95% CI, 0.40-0.89; P = .01).

However, the results for OS among patients with EGFR and ALK wild-type tumors who had high or intermediate PD-L1 expression, although numerically longer, did not cross the prespecified alpha boundary (median, 18.2 months for atezolizumab and 14.9 months for chemotherapy; stratified HR for death, 0.72; 95% CI, 0.52-0.99; P = .04). The OS for this group was not formally tested in accordance with statistical analysis plan, the authors wrote.

The median overall survival among these patients was 17.5 months with atezolizumab and 14.1 months with chemotherapy (stratified HR for death, 0.83; 95% CI, 0.65-1.07).

PFS was 8.1 months for atezolizumab and 5.0 months for chemotherapy (stratified HR for disease progression or death, 0.63; 95% CI, 0.45-0.88). Among patients with EGFR and ALK wild-type tumors who had high or intermediate PD-L1 expression, PFS was 7.2 months for atezolizumab and 5.5 months for chemotherapy (stratified HR or disease progression or death, 0.67; 95% CI, 0.52-0.88).

Looking at results by blood-based tumor mutational burden score of at least 16, 389 of the 554 patients with EGFR and ALK wild-type tumors with any PD-L1 expression could be evaluated; there, OS and PFS favored atezolizumab as well. Median OS was 13.9 months for atezolizumab and 8.5 months for chemotherapy group (unstratified HR for death, 0.75; 95% CI, 0.41-1.35). Median PFS was 6.8 months for atezolizumab group and 4.4 months for chemotherapy (unstratified HR for disease progression or death, 0.55; 95% CI, 0.33-0.92).

Safety results showed that adverse events occurred in 90.2% of the patients on atezolizumab and in 94.7% on chemotherapy. The safety profile was consistent with previous studies, the authors said.

Atezolizumab was approved by the FDA in May as an initial treatment for adults with this type of NSCLC. Genentech funded the trial and collaborated with the authors.

Reference

Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1–selected patients with NSCLC. N Engl J Med. 2020; 383:1328-1339. Doi: 10.1056/NEJMoa1917346