Non-Small Cell Lung Cancer · Medical · Advanced / Metastatic

KEYNOTE-189

In untreated metastatic nonsquamous NSCLC without EGFR/ALK alterations, does pembrolizumab added to pemetrexed–platinum improve survival?

Trial design and population

Population / eligibility

616 patients with untreated metastatic nonsquamous NSCLC without sensitizing EGFR or ALK alterations; all PD-L1 levels were included.

Intervention vs comparator

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles plus pemetrexed and cisplatin/carboplatin, followed by pemetrexed maintenance, vs placebo plus chemotherapy.

Sample size

616

Primary endpoint

Overall survival and progression-free survival

Key results

At 5-year follow-up, OS HR was 0.60 (95% CI 0.50–0.72) and PFS HR 0.50 (95% CI 0.42–0.60). Five-year OS was 19.4% vs 11.3%; benefit was observed across PD-L1 subgroups.

Source-reported outcome visualization

5-year overall survival · 5 years

Pembrolizumab + chemo

19.4 %

Placebo + chemo

11.3 %

Bars are scaled to the larger reported group value; endpoint, unit and horizon are labelled. Values are source-reported, not estimated from medians.

Absolute Effect

Absolute 5-year OS gain 8.1 percentage points; NNT 13 based on 5-year OS.

NNT: 13 based on 5-year OS. Use only at the stated endpoint/time horizon; median survival differences are not converted into NNT.

NNH: Not quantifiable. Grade 3–5 adverse events are common with platinum–pemetrexed in both groups. Pembrolizumab adds immune-mediated pneumonitis, colitis, hepatitis and endocrinopathies, occasionally fatal. NNH not calculated without a matched fixed-time excess-harm endpoint.

Time-to-event hazard ratios and median survival are not treated as absolute risk differences. Where no defensible fixed-time NNT/NNH is available, the source-reported endpoint is visualized instead.

Safety and treatment burden

Grade 3–5 adverse events are common with platinum–pemetrexed in both groups. Pembrolizumab adds immune-mediated pneumonitis, colitis, hepatitis and endocrinopathies, occasionally fatal. NNH not calculated without a matched fixed-time excess-harm endpoint.

Follow-up, maturity and limitations

Follow-up: Five-year follow-up analysis.

Excludes sensitizing EGFR/ALK alterations. Molecular drivers, histology, performance status and immunotherapy contraindications affect applicability.

Clinical interpretation

Adding pembrolizumab to pemetrexed–platinum improves long-term survival in first-line metastatic nonsquamous NSCLC without actionable EGFR/ALK drivers.

Current-practice context · reviewed 20 October 2026

This page separates the original trial findings from contemporary treatment sequencing. Confirm current guidelines, local regulatory status, biomarker requirements, prior treatment exposure and patient-specific contraindications before applying the evidence. Historical comparators may no longer represent the current standard; subgroup findings and immature endpoints are labelled rather than generalized.

Primary and authoritative sources

Gandhi L, et al. Pembrolizumab plus Chemotherapy in Metastatic NSCLC. NEJM. 2018. Source ↗

Five-year KEYNOTE-189 outcomes. JCO. 2023. Source ↗

ClinicalTrials.gov NCT02578680 Source ↗