FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 Stage III-IVA cervical cancer

Regulatory approval: On Jan 12, 2024, the FDA approved pembrolizumab (Keytruda) in combination with chemoradiotherapy (CRT) for patients with FIGO 2014 Stage III–IVA cervical cancer. The decision was supported by KEYNOTE-A18 (NCT04221945), which showed a statistically significant progression-free survival (PFS) benefit in the overall population; exploratory subgroup results suggested the benefit was primarily driven by the Stage III–IVA cohort. Overall survival data were not mature at the time of the PFS analysis.

FDA approval (Jan 12, 2024): pembrolizumab + CRT in FIGO 2014 Stage III–IVA cervical cancer

The US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck) with chemoradiotherapy (CRT) for patients with FIGO 2014 Stage III–IVA cervical cancer.

Key evidence: KEYNOTE-A18 (NCT04221945)

  • Design: multicenter, randomized, double-blind, placebo-controlled trial (n=1060) enrolling patients with cervical cancer who had not previously received definitive surgery, radiation, or systemic therapy.
  • Population included 596 patients with FIGO 2014 Stage III–IVA disease and 462 with FIGO 2014 Stage IB2–IIB, node-positive disease.
  • Treatment: pembrolizumab 200 mg q3w (or placebo) for 5 cycles with CRT, followed by pembrolizumab 400 mg q6w (or placebo) for 15 cycles.
  • CRT: cisplatin 40 mg/m² IV weekly for 5 cycles (optional 6th) plus EBRT followed by brachytherapy.

Outcomes

  • Major endpoints: investigator-assessed PFS (RECIST v1.1 or histopathologic confirmation) and OS.
  • The trial showed a statistically significant PFS improvement in the overall population.
  • Exploratory subgroup (Stage III–IVA): PFS HR 0.59 (95% CI 0.43–0.82); PFS events 21% vs 31% (pembrolizumab vs placebo).
  • Exploratory subgroup (Stage IB2–IIB): PFS HR 0.91 (95% CI 0.63–1.31).
  • OS data were not mature at the time of PFS analysis.

Safety and dosing (label highlights)

Common adverse reactions (≥10%) included nausea, diarrhea, vomiting, UTI, fatigue, hypothyroidism, constipation, decreased appetite, weight loss, abdominal pain, pyrexia, hyperthyroidism, dysuria, rash, and pelvic pain. Recommended dosing: 200 mg IV q3w or 400 mg IV q6w until progression/unacceptable toxicity or up to 24 months; administer pembrolizumab before CRT when given the same day.

The review was conducted under Project Orbis, with collaboration from Australia’s TGA and Brazil’s ANVISA (other agency reviews ongoing).

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