Recently, the European Commission has approved cemiplimab-rwlc (Libtayo), manufactured by US-based Regeneron, as monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer whose disease has progressed during or after platinum-containing chemotherapy. The results of the trial showed that this therapy significantly improved patient survival and had a good safety profile.
Cervical cancer is the fourth leading cause of cancer deaths in women worldwide and is more common in women aged 35 to 44 years. There are approximately 600,000 new cases of cervical cancer and 350,000 cervical cancer deaths worldwide each year. Almost all cases are caused by human papillomavirus (HPV) infection, of which about 80% are squamous cell carcinomas and most of the rest are adenocarcinomas.
Cervical cancer is usually curable if detected early and treated effectively, but treatment options are limited if it reaches an advanced stage.
Basis for approval
The approval of Libtayo is based on the results of the Phase 3 clinical trial EMPOWER-Cervical 1 (NCT03257267). The primary objective of the trial is to evaluate the efficacy of Libtayo as a monotherapy compared to chemotherapy in patients over 18 years of age with recurrent or metastatic cervical cancer whose disease has progressed following platinum-based chemotherapy.
This was an open-label, multi-centre, global phase 3 trial enrolling 608 patients from 14 countries or territories.
The mean age of patients enrolled was 51 years (range 22 to 87 years) and included patients with squamous, adenocarcinoma and adenosquamous carcinoma of the cervix. Of these patients, 77.8% had squamous cell carcinoma and 22.2% had adenocarcinoma or adenosquamous carcinoma.
Patients were eligible for inclusion regardless of their PD-L1 expression. Other inclusion criteria included patients with an ECOG fitness status of 0 or 1 and adequate organ function. Patients were also required to have received prior treatment with bevacizumab (Avastin) unless there was a clinically documented reason why it was not given.
Patients were randomly assigned to receive Libtayo treatment or chemotherapy drugs (including pemetrexed, vincristine, topotecan, irinotecan or gemcitabine) once every three weeks.
The primary endpoint of the trial was overall survival, with key secondary endpoints including progression-free survival, objective remission rate, duration of remission and safety.
Trial results
The trial results showed that Libtayo reduced the overall risk of death for patients by 31%, including a 27% reduction in the risk of death for patients with squamous cervical cancer.
Other data showed that
In the overall patient group, the mean overall survival of patients treated with Libtayo was 12 months compared to 8.5 months in the chemotherapy group.
In the cohort of patients with squamous cervical cancer, the average overall survival of patients treated with Libtayo was 11.1 months compared to 8.8 months in the chemotherapy group.
In the overall patient group, the objective remission rate for patients treated with Libtayo was 16.4% compared to 6.3% in the chemotherapy group.
In the cervical squamous cancer patient group, the objective remission rate for patients treated with Libtayo was 17.6% compared to 6.7% in the chemotherapy group.
In the overall patient group, the mean duration of remission for patients treated with Libtayo was 16.4 months compared to 6.9 months in the chemotherapy group.
As can be seen, there was a significant improvement in all survival data for patients treated with Libtayo compared to chemotherapy.
Safety
In terms of safety, no new safety signals were observed in patients treated with Libtayo in the trial.
Adverse events (AEs) were reported in 88.3% of patients treated with Libtayo compared to 91.4% of patients treated with chemotherapy. 45.0% and 53.4% of patients in the Libtayo and chemotherapy groups, respectively, experienced grade 3 or higher AEs.
Grade 3 or higher adverse reactions that occurred more frequently in the Libtayo group than in the chemotherapy group included urinary tract infections, malaise, arthralgia and fever.
About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was developed on Regeneron's proprietary VelocImmune technology platform.
Libtayo was previously approved by the European Union (EU) for the treatment of selected patients with advanced basal cell carcinoma (BCC), advanced squamous cell carcinoma of the skin (CSCC) and advanced non-small cell lung cancer (NSCLC).
Various trials on Libtayo are currently underway to investigate the efficacy of Libtayo as a monotherapy and in combination with various conventional or novel therapies in other solid tumours or haematological cancers.
"While some progress has been made in the prevention and treatment of cervical cancer, treatment options remain limited for patients with recurrent or metastatic cervical cancer." Israel Lowy, M.D., Senior Vice President, Cancer Translational and Clinical Sciences, Regenerative Pharma, said in a press release.
"Libtayo is the first PD-1 inhibitor to be shown in a Phase 3 trial to significantly improve patient survival compared to chemotherapy. This is the fourth approval of Libtayo by the European Commission, further extending the applicable patient population to patients with advanced cervical cancer and allowing access and benefit regardless of the patient's PD-L1 expression level."
Dr Ignace Vergote, gynaecological oncologist at the University Hospital Leuven in Belgium and Vice-Chair of the trial's Steering Committee, also said, "This trial is a landmark and represents an important advance in the treatment of patients with recurrent or metastatic cervical cancer, offering a new treatment option for this group of gynaecological cancer patients. "
