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KEYNOTE-407 — pembrolizumab plus chemotherapy in metastatic LUSC

One-paragraph summary

KEYNOTE-407 randomized 559 untreated metastatic squamous NSCLC patients to pembrolizumab or placebo added to carboplatin plus paclitaxel or nab-paclitaxel for four cycles, followed by pembrolizumab/placebo maintenance. Pembrolizumab improved both OS and PFS across PD-L1 strata without a large increase in the overall rate of grade ≥3 adverse events, establishing a first-line LUSC-specific standard.

Initial quantitative findings

Outcome Pembrolizumab combination Control Effect
Median OS 15.9 months 11.3 months HR 0.64 (95% CI 0.49–0.85)
Median PFS 6.4 months 4.8 months HR 0.56 (95% CI 0.45–0.70)
Grade ≥3 adverse events 69.8% 68.2% Similar overall frequency
Discontinuation for adverse events 13.3% 6.4% Higher with pembrolizumab

Long-term update

At median 56.9 months from randomization, the OS HR was 0.71 (95% CI 0.59–0.85) and PFS HR 0.62 (95% CI 0.52–0.74). Five-year OS was 18.4% versus 9.7% ([PMID 36735893](https://pubmed.ncbi.nlm.nih.gov/36735893/){target="_blank" rel="noopener"}). The 55 patients who completed 35 cycles were a survivor-selected group; their 90.9% response rate and subsequent survival must not be projected onto all starters.

Patient-reported outcomes

Global health/quality of life was maintained or improved with the pembrolizumab combination. At week 18, the between-group difference was 4.9 points (95% CI 1.4–8.3) ([PMID 31751163](https://pubmed.ncbi.nlm.nih.gov/31751163/){target="_blank" rel="noopener"}). Average preservation does not remove severe individual immune or cytotoxic toxicity.

Limitations

  • ECOG 0–1 trial population.
  • Excluded actionable EGFR/ALK disease and clinically difficult comorbidities.
  • Maintenance design combines induction and ongoing pembrolizumab effects.
  • Control crossover/subsequent immunotherapy can affect long-term OS interpretation.
  • PD-L1 subgroup consistency does not mean identical absolute benefit in every stratum.

Why it matters

KEYNOTE-407 is the most directly applicable first-line phase III trial for metastatic LUSC. It preserves the necessary squamous chemotherapy backbone while adding the class that finally generated durable survival tails.

Cited by wiki pages

  • Overview
  • Immunotherapy
  • Systemic therapy
  • Chemotherapy and histology constraints
  • Biomarkers
  • Guidelines
  • Clinical-trials landscape

Verified citation

Paz-Ares L, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379:2040–2051. [PMID 30280635](https://pubmed.ncbi.nlm.nih.gov/30280635/){target="_blank" rel="noopener"}