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KEYNOTE-A18 mature OS — Pembrolizumab + chemoradiation in high-risk locally advanced cervical cancer

Abstract: Plenary V mature OS · Session: Monday April 13, 2026 (cervical Plenary) · Simultaneous publication: TBD (likely JCO mature OS update)

Headline: Long-term OS HR 0.73 with 48-month OS 75.4% vs 70.2% — durable confirmation of pembrolizumab + chemoradiation as 1L SOC for high-risk (stage IB–IVA) locally advanced cervical cancer.

At a glance

  • Sponsor / cooperative groups: Merck · ENGOT-cx11 / GOG-3047
  • PI / presenter: Apr 13 Plenary V (presenter TBD)
  • NCT ID: NCT04221945
  • Phase / arms / N: Phase 3 randomized double-blind; 1,060 patients (529 pembro + CCRT vs 531 placebo + CCRT)
  • Primary endpoint(s): PFS and OS (dual primary); mature OS at SGO 2026
  • Indication / line: Locally advanced cervical cancer, high-risk (FIGO 2014 Stage IB2–IIB node+ or III–IVA)
  • Comparator: Placebo + cisplatin-based chemoradiation
  • Session: Plenary V (Day 4, Apr 13)

Headline result

Mature OS HR 0.73 (95% CI 0.57–0.94). 36-month OS 81.8% vs 74.4%; 48-month OS 75.4% vs 70.2%. Curves continue to separate over time consistent with durable immune memory. No new safety signals over extended follow-up.

Mechanism / class

Pembrolizumab is a humanized IgG4 anti–PD-1 monoclonal antibody. KEYNOTE-A18 was the registrational trial for the 2024 FDA approval of pembrolizumab + CCRT in high-risk LACC. The 48-mo mature OS update consolidates the new SOC.

Trial design deep dive

Study architecture: Phase 3 randomized double-blind placebo-controlled, 1:1 to pembrolizumab 200 mg Q3W + cisplatin-based CCRT for 5 cycles → pembrolizumab 400 mg Q6W maintenance for up to 15 additional cycles, vs placebo + CCRT → placebo maintenance. 1,060 patients (529 vs 531). Stratification by planned external beam RT (IMRT/VMAT vs non-IMRT), stage (IB2–IIB node+ vs III–IVA), and planned total RT dose. Multinational ENGOT-cx11/GOG-3047 cooperative-group footprint.

Endpoint definitions: PFS by investigator assessment per RECIST 1.1 (primary); OS (dual primary, gated per hierarchical testing). The SGO 2026 readout is the mature 48-month OS update following the primary OS readout at ESMO 2024 (HR 0.67 interim). Secondary endpoints include 24/36/48-mo OS landmark rates, PRO/QoL (EORTC QLQ-C30, CX24), and safety.

Key subgroup analyses: PD-L1 CPS subgroups (≥1, ≥10) reserved for ASCO 2026 biomarker follow-up. Stage (IB2–IIB node+ vs III–IVA), histology (squamous vs adenocarcinoma), HPV status, and geographic region pre-specified — all consistently favored pembro per the interim. RT-modality subgroup (IMRT vs non-IMRT) is uniquely important here given the global RT-technology gradient.

Comparator context: Cisplatin-based CCRT alone is the long-standing SOC; the 48-mo placebo-arm OS of 70.2% is consistent with historical high-risk LACC benchmarks (~65–72% at 4-5 yr). The 5.2-percentage-point absolute gain at 48 mo translates to a clinically meaningful durable cure-fraction enrichment.

FDA implications: Confirmatory — full approval in place since 2024; mature OS update locks in NCCN preferred status and supports global label expansion in remaining ex-US markets.

Discussant takeaway

Plenary V framing: the 48-mo OS curves at 75.4% vs 70.2% represent durable cure-fraction enrichment with an immune-modulated approach in a setting historically defined by chemoradiation alone. Reinforces molecular biomarker (PD-L1) investigation in follow-up analyses.

Practice-changing verdict

Yes (confirmatory). Pembro + CCRT is already 1L SOC for high-risk LACC; mature 48-mo OS data confirm the magnitude and durability of benefit. NCCN cervical guidelines reinforced.

  • Other SGO 2026: InnovaTV 205 Arm H (tisotumab vedotin 1L recurrent cervical); TroFuse-036 (sac-TMT maintenance post-CCRT); IBI130 (anti-TROP2 ADC)
  • AACR 2026: Cervical immunobiology sessions
  • ASCO 2026: Expected biomarker correlates + PD-L1 subgroup analyses
  • ESMO 2026: European subgroup follow-up

Sources