Clinical trialPhase 3Cervical cancer

First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826

JCO · 2023All-comer population: 617 patients; PD-L1 CPS ≥1 population: 548 patients; CPS ≥10 population: 317 patients

Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, et al. JCO. 2023. 41:5505-5511

Study type: Clinical trial
Study name: KEYNOTE-826
Phase: Phase 3
Design: Double-blind, placebo-controlled phase 3 trial (updated report with final overall survival results)
Sample size: All-comer population: 617 patients; PD-L1 CPS ≥1 population: 548 patients; CPS ≥10 population: 317 patients
Source: JCO · 2023

In plain words

In this study, women with advanced cervical cancer that had persisted, come back or spread were given, in addition to chemotherapy, either the immunotherapy drug pembrolizumab or a placebo. After longer follow-up, patients who received pembrolizumab lived much longer; for example, across all patients the median survival was about 26.4 months versus 16.8 months. Severe side effects were slightly more common in the pembrolizumab group (82.4% versus 75.4%).

Key results

28.6 vs 16.5 months

Median overall survival — CPS ≥1 population (548 patients)

HR for death 0.60 (95% CI 0.49–0.74)

26.4 vs 16.8 months

Median overall survival — all comers (617 patients)

HR 0.63 (95% CI 0.52–0.77)

29.6 vs 17.4 months

Median overall survival — CPS ≥10 population (317 patients)

HR 0.58 (95% CI 0.44–0.78)

39.1 months

Median follow-up at the final data cut-off (3 October 2022)

Range 32.1–46.5 months

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

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

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. Analyses were done in three populations: patients with a PD-L1 combined positive score (CPS) of 1 or more, all comers, and patients with a CPS of 10 or more.

According to the FDA label for pembrolizumab: patients had not received previous chemotherapy except chemotherapy given concurrently with radiotherapy (as a radiosensitiser) and were enrolled regardless of PD-L1 expression; patients with autoimmune disease requiring systemic treatment in the past 2 years or conditions requiring immunosuppression were excluded.

Endpoints

This paper reports the final overall survival (OS) results, tested per protocol in the PD-L1 CPS ≥1, all-comer and CPS ≥10 populations. Other endpoints are not described in the abstract.

Safety and side effects

The incidence of grade 3 or higher adverse events was 82.4% with pembrolizumab + chemotherapy and 75.4% with placebo + chemotherapy.

Clinical significance and place in guidelines

The final overall survival results confirm that adding pembrolizumab to platinum-based chemotherapy (with or without bevacizumab) in patients with persistent, recurrent or metastatic cervical cancer maintains a clinically meaningful survival improvement over long-term follow-up. Regulatory approval status and clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.

Limitations

The abstract does not give enough information on eligibility criteria, chemotherapy and bevacizumab doses, or secondary endpoints. Further details should be checked in the full text of the paper.

Original article (DOI)PubMed

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.