The European Commission has granted approval to pembrolizumab (Keytruda) for two new indications in gynecologic cancers, specifically endometrial and cervical cancer. This decision impacts the treatment landscape for adult patients in Europe, offering new hope for those with advanced stages of these diseases.
The approvals are based on data derived from the phase 3 KEYNOTE-868 and KEYNOTE-A18 trials. These studies evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy or chemoradiotherapy for endometrial and cervical cancers, respectively.
KEYNOTE-868: Endometrial Carcinoma
In the KEYNOTE-868 trial, pembrolizumab combined with carboplatin and paclitaxel demonstrated a statistically significant improvement in progression-free survival (PFS) for patients with advanced or recurrent endometrial carcinoma. The study enrolled patients with newly diagnosed stage III or IVA endometrial cancer or recurrent/stage IVB endometrial cancer. Patients were randomized 1:1 to receive either pembrolizumab or placebo in combination with chemotherapy.
For the mismatch repair-deficient (dMMR) cohort, the median PFS was not reached (NR; 95% CI, 30.6-NR) in the pembrolizumab plus chemotherapy arm, compared to 7.6 months (95% CI, 6.4-9.9) in the placebo plus chemotherapy arm (HR, 0.30; 95% CI, 0.19-0.48; P < .001). The estimated 12-month PFS rates were 74% and 38%, respectively.
In the mismatch repair-proficient (pMMR) cohort, the median PFS was 13.1 months (95% CI, 10.5-18.8) in the pembrolizumab arm versus 8.7 months (95% CI, 8.4-10.7) in the placebo arm (HR, 0.54; 95% CI, 0.41-0.71; P < .001).
KEYNOTE-A18: Cervical Cancer
The KEYNOTE-A18 trial investigated pembrolizumab in combination with chemoradiotherapy for patients with locally advanced cervical cancer (FIGO 2014 stage III to IVA) who had not received prior definitive therapy. Patients were randomized to receive either pembrolizumab or placebo with cisplatin and external beam radiotherapy, followed by brachytherapy.
At a median follow-up of 17.9 months, the median PFS was NR in both the pembrolizumab plus chemoradiotherapy arm and the placebo plus chemoradiotherapy arm (HR, 0.70; 95% CI, 0.55-0.89; P = .0020). The 24-month PFS rates were 68% for the pembrolizumab arm versus 57% for the placebo arm.
The median overall survival (OS) was NR in both groups (HR, 0.73; 95% CI, 0.49-1.07). The 24-month OS rates were 87% in the pembrolizumab group and 81% in the placebo group.
Clinical Implications
These approvals represent a significant advancement in the treatment of endometrial and cervical cancers. According to Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, these pembrolizumab-based regimens have the potential to change the treatment paradigm for these cancers, which are among the most commonly diagnosed cancers among women in Europe. The expanded use of pembrolizumab offers utility ranging from earlier lines of therapy to treating advanced disease.
These EU approvals follow similar approvals by the FDA in January and June 2024 for the same indications, reinforcing the global recognition of pembrolizumab's efficacy in these gynecologic cancers.
