Cemiplimab (6) – Libtayo®

• Clinical trials
  • The C-POST trial is an ongoing, multicentre, double-blind, randomised controlled phase III trial comparing cemiplimab as monotherapy with placebo, in each case following surgery and subsequent radiotherapy.

Adults with cutaneous squamous cell carcinoma at high risk of recurrence following resection and radiotherapy; adjuvant treatment

• Consequently, for cemiplimab as adjuvant treatment of cutaneous squamous cell carcinoma following resection and radiotherapy in adult patients at high risk of recurrence, a non-quantifiable additional benefit compared with watchful waiting has been established.
• In summary, the G-BA therefore derives an indication for the established additional benefit with regard to the certainty of the finding (probability of additional benefit).
• mortality
  • No statistically significant difference was observed between the treatment groups for the endpoint of overall survival.
• Morbidity – failure of the curative treatment approach
  • Overall, for the endpoint ‘failure of the curative treatment approach’ – in both the main and sensitivity analyses – there is a statistically significant difference in favour of cemiplimab compared with watchful waiting, both for the event rate and for the time-dependent analysis.
  • It should be noted, however, that at the time of the second data cut-off, there were still a high number of early censorings for the DFS endpoint, suggesting that the duration of follow-up is not yet sufficient to allow for a definitive assessment of this endpoint.
  • The EMA has also criticised the duration of follow-up and originally called for a fixed follow-up period of 3 years.
  • As the present C-POST study only included patients who had undergone R0 and R1 resections, it can therefore be assumed that patients in this therapeutic indication are being treated with a curative therapeutic approach.
• Morbidity – Symptoms (assessed using the EORTC QLQ-C30)
  • For all scales of the EORTC QLQ-C30 (overall health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), there were no statistically significant differences between cemiplimab and watchful waiting.
• Morbidity – Health status (assessed using the EQ-5D VAS)
  • No statistically significant difference was observed between the treatment groups.
• quality of life
  • For all functional scales of the EORTC QLQ-C30, there were no statistically significant differences between the treatment groups.
  • Overall, therefore, there is neither an advantage nor a disadvantage for cemiplimab in terms of health-related quality of life.
• Side effects – Serious adverse events (SAEs), severe adverse events (CTCAE grade ≥ 3), therapy discontinuation due to adverse events
  • For the endpoints SAE, severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs, a statistically significant disadvantage was observed in each case compared with the watch-and-wait approach.
• Side effects – Immune-mediated serious adverse events, immune-mediated severe adverse events (CTCAE ≥ 3)
  • For the endpoints immune-mediated SAE and immune-mediated severe AEs, a statistically significant difference was observed in each case, to the disadvantage of cemiplimab compared with watchful waiting.
• Side effects – Hypothyroidism (PT, adverse events)
  • For the specific AE of hypothyroidism (PT, AEs), there is a statistically significant disadvantage compared with a watch-and-wait approach for cemiplimab.
• Overall assessment
  • No statistically significant difference in overall survival was observed between the treatment groups.
  • Based on the results regarding symptoms, health status and health-related quality of life (assessed using the EORTC QLQ-C30 and EQ-5D-VAS), neither an advantage nor a disadvantage can be inferred for cemiplimab compared with watchful waiting.
  • With regard to the results on the failure of the curative treatment approach, presented as the recurrence rate and disease-free survival, a clear advantage of cemiplimab compared with watchful waiting is observed.
  • Preventing recurrence is an essential treatment objective in the present curative treatment setting.
  • It should be noted, however, that at the time of the second data cut-off, there was a high number of early censorings for the DFS endpoint, suggesting that the duration of follow-up is not yet sufficient to allow for a definitive assessment of the endpoint.
  • The EMA has also criticised the duration of follow-up and originally called for a fixed follow-up period of 3 years.
  • The results regarding side effects indicate a disadvantage for cemiplimab.
  • This is based on statistically significant differences to the detriment of cemiplimab in terms of serious adverse events (AEs), severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs.
  • In detail, there is a disadvantage for cemiplimab compared with a ‘watch-and-wait’ approach in terms of specific AEs.
  • Overall, the advantage in terms of the endpoint ‘failure of the curative approach’ is offset by a disadvantage regarding side effects.
  • Given the high number of early censorings, the extent of the improvement at the endpoint of failure of the curative approach cannot be reliably quantified.
  • However, the large difference between the treatment arms does not call the effect into question.
  • A longer observation period would be necessary to enable quantification of the extent of the improvement achieved.
  • Although the disadvantage regarding side effects is classified as significant, this does not lead to a downgrading of the overall conclusion on additional benefit.

Courtesy translation only, please refer to the German original.