"Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer". The New England Journal of Medicine. 2016. 375(19):1823-1833. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with previously untreated advanced non–small-cell lung cancer (NSCLC) with PD-L1 expression on at least 50% of tumor cells, how does pembrolizumab compare with platinum-based chemotherapy?

Bottom Line

In previously untreated advanced NSCLC patients with PD-L1 expression on at least 50% of tumor cells, pembrolizumab significantly improved progression-free and overall survival with fewer adverse events compared to platinum-based chemotherapy.

Major Points

Advanced NSCLC patients with high PD-L1 expression often have limited treatment options beyond chemotherapy. Pembrolizumab, a PD-1 inhibitor, has shown promising results in such patients.

Guidelines

This study may influence guidelines to consider pembrolizumab for first-line treatment in advanced NSCLC patients with PD-L1 expression on at least 50% of tumor cells.

Design

Open-label, phase 3 randomized controlled trial.
N=305 patients.
Pembrolizumab vs. investigator's choice of platinum-based chemotherapy.

Population

305 patients with untreated, stage IV NSCLC with PD-L1 expression on ≥50% tumor cells.
Inclusion Criteria: Aged ≥18 years, ECOG performance-status score 0 or 1, and life expectancy ≥3 months. No sensitizing EGFR mutations or ALK translocations.
Exclusion Criteria: Systemic glucocorticoids or immunosuppressive treatment, untreated brain metastases, active autoimmune disease, interstitial lung disease, pneumonitis history.

Interventions

Pembrolizumab (200 mg IV every 3 weeks for 35 cycles) vs. investigator's choice of platinum-based chemotherapy (4 to 6 cycles).

Outcomes

Primary Outcome: Progression-free survival assessed by central radiologic review.
Secondary Outcomes: Overall survival, objective response rate, safety.

Criticisms

Open-label design could introduce bias. Low number of deaths and confounding effect of crossover design. Limited generalizability to patients with low PD-L1 expression.

Funding

The trial was funded by Merck, the developer of pembrolizumab.

Further Reading

Additional sources and research for further reading.