Clinical trialPhase 3Cervical cancer

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer

N Engl J Med · 2021617 patients (548 with CPS ≥1)

Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, et al. N Engl J Med. 2021. 385:1856-1867

A newer report of this study has been published: Pembrolizumab Plus Chemotherapy for Cervical Cancer: An Exploratory Analysis of the KEYNOTE-826 Randomized Clinical Trial (2026)

Study type: Clinical trial
Study name: KEYNOTE-826
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial
Sample size: 617 patients (548 with CPS ≥1)
Source: N Engl J Med · 2021
Trial registration: NCT03635567

In plain words

In cervical cancer that has come back or spread to distant organs, adding the immunotherapy drug pembrolizumab to the usual chemotherapy helped patients live considerably longer: in patients with the PD-L1 marker, median survival rose from about 16.5 months to 28.6 months. Before treatment starts, the tumour sample is tested for PD-L1.

Key results

10.4 vs 8.2 months

Median PFS (CPS ≥1)

HR 0.62 (95% CI 0.50–0.77); P<0.001

53.0% vs 41.7%

24-month overall survival (CPS ≥1)

HR 0.64 (95% CI 0.50–0.81); P<0.001

28.6 vs 16.5 months

Final median overall survival (CPS ≥1)

HR 0.60 (95% CI 0.49–0.74); final analysis JCO 2023, median follow-up 39.1 months

26.4 vs 16.8 months

Final median overall survival (all patients)

HR 0.63 (95% CI 0.52–0.77)

Drugs in this study:Bevacizumab (Avastin)Carboplatin (Paraplatin)Cisplatin (Platinol)Paclitaxel (Taxol)Pembrolizumab (Keytruda)

Dose and schedule cards

Pembrolizumab + paclitaxel and platinum ± bevacizumab (KEYNOTE-826)

First-line persistent, recurrent or metastatic disease with PD-L1 CPS ≥1 (by an approved test)Cycle length: Every 21 daysOn the page “Cervical cancer” · Metastatic, persistent or recurrent disease: first line

First-line persistent, recurrent or metastatic disease with PD-L1 CPS ≥1 (by an approved test)

Drug	Dose	Route	Schedule
Pembrolizumab	200 mg (or 400 mg every 6 weeks per the label)	IV	Day 1 every 3 weeks, before chemotherapy
Paclitaxel	175 mg/m²	IV	Day 1
Cisplatin or carboplatin	Cisplatin 50 mg/m² or carboplatin AUC 5	IV	Day 1
Bevacizumab (at the physician’s discretion)	15 mg/kg	IV	Day 1

Cycle length: Every 21 days
Duration: Chemotherapy up to 6 cycles; pembrolizumab up to 35 cycles (about 2 years); all until progression or unacceptable toxicity

The most common grade 3–5 adverse events were anaemia (30.3% vs 26.9%) and neutropenia (12.4% vs 9.7%). Source for dosing: protocol NCT03635567.

On the page “Cervical cancer” · Metastatic, persistent or recurrent disease: first line

KEYNOTE-826

Recurrent or metastatic cervical cancer, first lineCycle length: Every 21 daysOn the page “Pembrolizumab in cervical cancer: with chemoradiotherapy and in metastatic disease”

Recurrent or metastatic cervical cancer, first line

Drug	Dose	Route	Schedule
Pembrolizumab	200 mg	IV	Day 1
Paclitaxel	175 mg/m²	IV	Day 1
Cisplatin 50 mg/m² or carboplatin AUC 5		IV	Day 1
Bevacizumab (optional)	15 mg/kg	IV	Day 1

Cycle length: Every 21 days
Duration: Chemotherapy 6 cycles; pembrolizumab up to 35 cycles

As in KEYNOTE-826.

Dose source:.

On the page “Pembrolizumab in cervical cancer: with chemoradiotherapy and in metastatic disease”

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Pembrolizumab + chemotherapy ± bevacizumab

Pembrolizumab 200 mg IV on day 1 of each 21-day cycle for up to 35 cycles (about 2 years), plus investigator's choice of chemotherapy for up to 6 cycles: paclitaxel 175 mg/m² + cisplatin 50 mg/m², or paclitaxel 175 mg/m² + carboplatin AUC 5 (all IV, day 1); each with or without bevacizumab 15 mg/kg IV (at the investigator's discretion). All treatments continued until disease progression or toxicity.

2Placebo + chemotherapy ± bevacizumab

Placebo (normal saline or dextrose) IV on day 1 of each 21-day cycle for up to 35 cycles (about 2 years), plus investigator's choice of chemotherapy for up to 6 cycles: paclitaxel 175 mg/m² + cisplatin 50 mg/m², or paclitaxel 175 mg/m² + carboplatin AUC 5 (all IV, day 1); each with or without bevacizumab 15 mg/kg IV (at the investigator's discretion). All treatments continued until disease progression or toxicity.

Source of the regimen details: Abstract of the paper (pembrolizumab 200 mg every 3 weeks for up to 35 cycles) and ClinicalTrials.gov NCT03635567 (chemotherapy and bevacizumab doses)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with persistent, recurrent or metastatic cervical cancer who had not previously received systemic chemotherapy for this stage and were not candidates for curative treatment.

Patients with autoimmune disease requiring systemic treatment in the past 2 years or conditions requiring immunosuppression were excluded; randomisation was stratified by metastatic status at diagnosis, the decision to use bevacizumab and PD-L1 status (CPS less than 1, 1 to less than 10, 10 or more) (FDA label for pembrolizumab).

Endpoints

Dual primary endpoints: progression-free survival and overall survival, tested in order in patients with PD-L1 CPS ≥1, in the whole intention-to-treat population and in patients with CPS ≥10.

Safety and side effects

The most common grade 3 to 5 adverse events were anaemia (30.3% versus 26.9%) and neutropenia (12.4% versus 9.7%). In the final analysis, grade 3 or higher adverse events occurred in 82.4% of the pembrolizumab group and 75.4% of the placebo group.

Clinical significance and place in guidelines

In October 2021 the FDA approved pembrolizumab with chemotherapy ± bevacizumab for PD-L1-positive tumours (CPS ≥1). The NCCN guideline (version 2.2026) lists this combination as a category 1 preferred first-line option in PD-L1-positive recurrent/metastatic disease, and ESGO/ESTRO/ESP 2023 also recommends it at level [I, A]. The final overall survival analysis (Monk et al., JCO 2023) confirmed a durable benefit.

Limitations

Use of bevacizumab was not randomised; the benefit in patients with CPS less than 1 (a small group) is unclear; most patients had squamous histology.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.