#Keynote 407 plus

KEYNOTE-024 showed 31.2% of grade 3-5 adverse events (AEs) in the pembrolizumab group compared with 53.3% in the chemotherapy group. Given that the survival advantages provided by IO compared with chemo IO and chemotherapy alone are minimal, the decision for first-line therapy may be guided by disease burden and safety considerations from these agents. The relative parity in the findings from these studies is summarized in FIGURES 1A AND 1B.

#Keynote 407 plus

In CheckMate 9LA (NCT03215706), 8 which compared nivolumab plus ipilimumab plus chemo-therapy with chemotherapy alone, investigators reported a median OS of 18 months compared with 12.6 months, respectively, with a hazard ratio of 0.66 for patients with PD-L1 TPS of at least 50%, assessed by 28-8 IHC. In the subgroup analysis of patients with PD-L1 TPS of at least 50%, those who received dual immunotherapy had an OS of 21.2 months (95% CI, 15.5-38.2) compared with 14.0 months (95% CI, 10.0-18.6) in the chemotherapy- alone population with a hazard ratio of 0.70 (95% CI, 0.55-0.90).

In CheckMate 227 (NCT02477826), 7 nivolumab (Opdivo) plus ipilimumab (Yervoy) was compared with chemo-therapy. 6 Ipilimumab-Based Immunotherapy Combinations Final analysis data presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program showed a median OS of 27.7 months for the population of patients with PD-L1 TPS of at least 50%, evaluated by IHC 22C3 (95% CI, 20.4-NR) compared with 10.1 months (95% CI, 7.5-22.0) in the chemotherapy group with a hazard ratio of 0.59 (95% CI, 0.40-0.86). The KEYNOTE-189 (NCT02578680) 5 study compared pembrolizumab plus chemo-therapy with chemotherapy alone in a nonsquamous NSCLC population. High PD-L1 expression in IMpower110 was defined as PD-L1 tumor cell expression of at least 50% or tumor-infiltrating immune cell expression of at least 10% by SP142 IHC.

4 The OS for patients with high PD-L1 expression was 20.2 months with atezolizumab (95% CI, 16.5-not evaluable ) com-pared with 13.1 months in the chemotherapy arm (95% CI, 7.4-16.5) with a hazard ratio of 0.59 (95% CI, 0.40-0.89). These data indicate a durable effect at 1 year following completion of treatment.Ī population of patients with PD-L1 expression of at least 50% also demonstrated benefit with IO in the IMpower110 study (NCT02409342), in which investigators evaluated the efficacy of atezolizumab (Tecentriq) versus chemotherapy. Of note, the pembrolizumab regimen included up to 2 years of IO and reported a 31% survival rate for those who received IO at 3 years. The study confirmed the benefit of pembrolizumab compared with chemotherapy in the population of patients with PD-L1 TPS of at least 50%, also evaluated by IHC 22C3. Eligible patients were adults (≥18 years). 2 The KEYNOTE-042 (NCT02220894) 3 open-label, phase 3 study was conducted in 213 medical centers in 32 countries. Investigators reported a median over-all survival (OS) of 30.0 months (95% CI, 18.3–not reached ) in the pembrolizumab arm and 14.2 months (95% CI, 9.8-19.0) in the chemotherapy arm with a hazard ratio of 0.63 (95% CI, 0.47-0.86) in patients with a PD-L1 tumor proportion score (TPS) of at least 50% by immunohistochemistry (IHC) 22C3 pharmDX assay. In KEYNOTE-024 (NCT02142738), 1 pembrolizumab (Keytruda) was com-pared with platinum-based chemotherapy. Several studies have evaluated the role of immunotherapy as monotherapy in patients with PD-L1 expression of at least 50%. PD-L1–High Metastatic NSCLC: Immunotherapy Alone

Data from completed studies evaluating IO alone or in combination with chemotherapy show that a breakdown of populations by PD-L1 status and additional considerations such as toxicity profiles should guide treatment decisions. Recent studies have demonstrated a role for immuno-oncology (IO) agents in the first line, but the added benefit of combining them with chemotherapy (chemo IO) is not clear in all populations. Despite these advances, the best treatment options for patients with nondriver met-astatic NSCLC remain unclear. Progress made in the area of targeted therapies has pushed treatment with small-molecule inhibitors to the front-line setting for patients with aberrations in EGFR, ALK, ROS1, BRAF, MET, and RET. The therapeutic landscape for first-line treatment of metastatic non–small cell lung cancer (NSCLC) contains many options.