Pembrolizumab (24) – Keytruda®

• Clinical trials
  • The KEYNOTE 158 trial is a multicentre, open-label, single-arm Phase II trial that has been ongoing since February 2016.
  • The KEYNOTE 775 trial is a multicentre, randomised, actively controlled, open-label Phase III trial comparing pembrolizumab in combination with lenvatinib against standard of care therapy, with a choice of doxorubicin or paclitaxel.

Adult female patients with advanced or recurrent endometrial cancer with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), and whose disease has progressed during or following prior platinum-based therapy at any stage of the disease, where curative surgical treatment or radiotherapy is not an option

• The additional benefit is not proven.
• Overall, the data presented are not sufficient to demonstrate additional benefit compared with the appropriate comparator therapy, and therefore no additional benefit of pembrolizumab as monotherapy in adult female patients with advanced or recurrent endometrial cancer with MSI-H or dMMR, and whose disease has progressed during or after prior platinum-based therapy, at any stage of the disease, when curative surgical treatment or radiotherapy is not an option, is not proven.
• mortality
  • The comparisons of individual arms submitted by the pharmaceutical manufacturer are naive comparisons without a bridge comparator and without adjustment for potentially relevant effect modifiers or prognostic factors.
• Morbidity – Progression-free survival
  • For the endpoints of progression-free survival and severe adverse events, the pharmaceutical manufacturer presents a descriptive comparison of the results from the two studies.
• Side effects – severe adverse events
  • For the endpoints of progression-free survival and severe adverse events, the pharmaceutical manufacturer provides a descriptive comparison of the results of the two studies.
• Health-related quality of life
  • The pharmaceutical manufacturer also presents the results relating to symptoms, health status and health-related quality of life from the KEYNOTE 158 study.
• Conclusion
  • The results from the KEYNOTE 158 trial alone are not suitable for assessing the additional benefit of pembrolizumab, as they do not allow for a comparison with the appropriate comparator therapy.
  • Due to the lack of randomisation, these comparisons are subject to inherent uncertainty and do not constitute an adequate method of indirect comparison. Furthermore, there are no effects for which it can be reliably ruled out that they are not solely the result of systematic bias.

Courtesy translation only, please refer to the German original.