Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Optimizing Patient Outcomes with PD‐1/PD‐L1 Immune Checkpoint Inhibitors for the First‐Line Treatment of Advanced Non–Small Cell Lung Cancer

“…Pembrolizumab was initially approved as first‐line monotherapy in patients with metastatic NSCLC and tumor PD‐L1 expression of 50% or greater based on results from the phase III trial KEYNOTE‐024 that showed improved PFS (median PFS 10.3 vs 6 mo; hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.37–0.68) and OS (median OS 30.0 vs 14.2 mo; HR 0.63, 95% CI 0.47–0.86) compared with chemotherapy . Recently, the Food and Drug Administration (FDA) lowered the PD‐L1 threshold to 1% or greater based on results from KEYNOTE‐042, a phase III trial that showed significantly longer OS in patients treated with pembrolizumab versus chemotherapy across PD‐L1 of 50% or greater (HR 0.69, 95% CI 0.56–0.85), 20% or greater (HR 0.77, 95% CI 0.64–0.92), and 1% or greater (HR 0.81, 95% CI 0.71–093) subpopulations . However, subgroup analysis by PD‐L1 1–49% showed that OS was not significantly different between pembrolizumab and chemotherapy (13.4 vs 12.1 mo; HR 0.92, 95% CI 0.77–1.11).…”

“…Pembrolizumab is the only ICI currently approved as monotherapy in the first‐line setting for treatment of patients with squamous or nonsquamous metastatic NSCLC and tumor PD‐L1 expression of 50% or greater (NCCN category 1) or 1–49% and cannot tolerate ICI plus chemotherapy (NCCN category 2B), based on data from the KEYNOTE‐042 and KEYNOTE‐024 trials discussed earlier . In addition, pembrolizumab was better tolerated than chemotherapy, with lower rates of grade 3–5 AEs in both the KEYNOTE‐042 (18% vs 41%) and KEYNOTE‐024 (31.2% vs 53.3%) trials.…”

“…The pivotal clinical trials for these treatments have been reviewed in depth, and results are summarized in Table . This review focuses on patient and treatment selection strategies to optimize clinical outcomes.…”

Class A CpG oligodeoxynucleotide inhibits IFN‐γ‐induced signaling and apoptosis in lung cancer

“…Thus, anti‐PD‐1 or anti‐PD‐L1 antibodies activate CTLs by inhibiting this binding in the tumor microenvironment . Compared to existing chemotherapies, anti‐PD‐1 antibody significantly prolonged the overall survival of patients with untreated advanced non‐small cell lung cancer …”

Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

“…In patients treated with anti‐CTLA‐4 monotherapy, the objective response rate (ORR) varied from 19% to 32% for melanoma . In patients receiving anti‐PD‐1 monotherapy, the reported ORR of melanoma, non‐small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and squamous cell carcinoma of the head and neck (SCCHN) was 45%, 39%, 25%, and 15%, respectively . In addition, immune‐mediated complications have been observed during ICB therapy .…”