Cemiplimab (4) – Libtayo®

• Clinical trials
  • The open-label, randomised, controlled Phase III EMPOWER-Cervical 1 trial included adult female patients with recurrent or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) who had experienced disease progression during or following platinum-based chemotherapy.
  • In the study arms, cemiplimab was compared with treatment as clinically indicated, with a choice of monotherapy with pemetrexed, topotecan, irinotecan, gemcitabine or vinorelbine (hereinafter: chemotherapy).

a) Adult female patients with recurrent or metastatic cervical cancer who have experienced disease progression during or after first-line platinum-based chemotherapy and for whom further antineoplastic therapy is an option

• Consequently, the G-BA has concluded that, for cemiplimab compared with treatment as clinically indicated, with a choice of monotherapy comprising nab-paclitaxel, vinorelbine, ifosfamide, topotecan, pemetrexed, irinotecan and pembrolizumab (for patients with PD-L1-positive metastatic cervical cancer) for patients with recurrent or metastatic cervical cancer who have experienced disease progression during or after platinum-based chemotherapy and for whom further antineoplastic therapy is an option, the G-BA has provided an indication of considerable additional benefit.
• Consequently, the certainty of the evidence for the identified additional benefit is classified as ‘indication’.
• mortality
  • Overall survival is defined in the EMPOWER-Cervical 1 trial as the time from randomisation to death from any cause.
  • For the endpoint of overall survival, a statistically significant difference was observed between the treatment groups in favour of cemiplimab compared with treatment as the clinician deems appropriate, involving the selection of monotherapy with nab-paclitaxel, vinorelbine, ifosfamide, topotecan, pemetrexed, irinotecan and pembrolizumab (for patients with PD-L1-positive metastatic cervical cancer) (hereinafter: chemotherapy).
  • The extent of the prolongation in overall survival achieved is considered a significant improvement.
• Morbidity – Progression-free survival (PFS)
  • In the Empower-Cervical 1 trial, PFS is defined as the period from randomisation to the first documented occurrence of disease progression or death from any cause, whichever occurs first.
  • A statistically significant difference in PFS was observed between the treatment groups, in favour of cemiplimab.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
• Morbidity – Symptoms (assessed using the EORTC QLQ-C30)
  • In the EMPOWER-Cervical 1 trial, patients’ symptoms are assessed using the symptom scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • For the endpoints of pain, nausea and vomiting, and loss of appetite, a statistically significant advantage was observed in favour of cemiplimab compared with chemotherapy.
• Health-related quality of life
  • Health-related quality of life is assessed in the EMPOWER-Cervical 1 trial using the EORTC QLQ-C30 questionnaire.
  • For the endpoints of physical functioning, role functioning and social functioning, a statistically significant difference was observed in favour of cemiplimab compared with the control arm.
• Side effects – severe adverse events (CTCAE grade ≥ 3)
  • For the endpoint of severe AEs (CTCAE grade ≥ 3), a statistically significant advantage was observed in favour of cemiplimab compared with chemotherapy.
• Side effects – Therapy discontinuations due to adverse events
  • For the endpoint of therapy discontinuations due to AEs, there was no statistically significant difference between the intervention and control arms.
• Side effects – Specific adverse events
  • For the other specific AE events – nausea (PT, AE) and disorders of the blood and lymphatic system (SOC, SAE) – a statistically significant advantage was observed in favour of cemiplimab compared with chemotherapy.
  • For the endpoint of liver and biliary disorders (SOC, severe AEs [CTCAE grade ≥ 3]), a statistically significant disadvantage was observed compared with chemotherapy.
• Overall view
  • For the endpoint of overall survival, a statistically significant difference was observed between the treatment groups in favour of cemiplimab compared with chemotherapy.
  • The extent of the prolongation in overall survival achieved is considered a significant improvement.
  • Symptoms were assessed in the EMPOWER-Cervical 1 trial using the symptom scales of the EORTC QLQ-C30. For the endpoints of pain, nausea and vomiting, and loss of appetite, a statistically significant advantage was observed in favour of cemiplimab compared with chemotherapy.
  • With regard to the health-related quality of life endpoint category (assessed using the EORTC QLQ-C30), a statistically significant difference in favour of cemiplimab compared with the control arm was observed for the endpoints of physical functioning, role functioning and social functioning.
  • For the endpoint category of AEs, an overall advantage can be identified for cemiplimab compared with chemotherapy, based on a statistically significant reduction in severe AEs (CTCAE grade ≥ 3) as well as predominant benefits regarding specific AEs.
  • Overall, the G-BA concludes that, for cemiplimab compared with treatment as clinically indicated—selecting monotherapy with nab-paclitaxel, vinorelbine, ifosfamide, topotecan, pemetrexed, irinotecan and pembrolizumab (for patients with PD-L1-positive metastatic cervical cancer) for female patients with recurrent or metastatic cervical cancer who have experienced disease progression during or after platinum-based chemotherapy and for whom further antineoplastic therapy is an option, the G-BA identifies a considerable additional benefit.

b) Adult female patients with recurrent or metastatic cervical cancer who have experienced disease progression during or after first-line platinum-based chemotherapy and for whom further antineoplastic therapy is not an option

• The additional benefit is not proven.
• The pharmaceutical manufacturer did not submit any data with the dossier to assess the additional benefit of cemiplimab in this patient group or in comparison with best supportive care.
• Consequently, additional benefit is not proven for patients for whom further antineoplastic therapy is not an option.

Courtesy translation only, please refer to the German original.