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PD-L1-selected patients: Atezolizumab for first-line treatment of metastatic non–small-cell lung cancer

The efficacy and safety of the anti–programmed death ligand 1 ( PD-L1 ) monoclonal antibody Atezolizumab ( Tecentriq ), as compared with those of Platinum-based chemotherapy, as first-line treatment for patients with metastatic non–small-cell lung cancer ( NSCLC ) with PD-L1 expression are not known.

Researchers have conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay.
Patients were assigned in a 1:1 ratio to receive Atezolizumab or chemotherapy.

Overall survival ( primary end point ) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat ( ITT ) population whose tumors were wild-type with respect to EGFR mutations or ALK translocations.
Within the population with EGFR and ALK wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden ( TMB ).

Overall, 572 patients were enrolled. In the subgroup of patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1 ( 205 patients ), the median overall survival was longer by 7.1 months in the Atezolizumab group than in the chemotherapy group ( 20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01 ).

Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the Atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups.

Overall and progression-free survival favored Atezolizumab in the subgroups with a high blood-based tumor mutational burden.

In conclusion, Atezolizumab treatment resulted in significantly longer overall survival than Platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. ( Xagena )

Herbst RS et al, N Engl J Med 2020; 383:1328-1339

XagenaMedicine_2020