Pembrolizumab (27) – 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 ABC-06 trial is a completed, multicentre, open-label, randomised, controlled Phase III trial in which adult patients with unresectable or metastatic biliary carcinoma, who had already received first-line treatment with cisplatin and gemcitabine, were randomised to the ASC (active symptom control) arm or the ASC arm in combination with folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX).

Adults with unresectable or metastatic biliary carcinoma with high-frequency microsatellite instability (MSI-H) or with a mismatch repair deficiency (dMMR) and disease progression during or after at least one previous course of treatment

• 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 additional benefit is not proven for pembrolizumab as monotherapy in adult patients with unresectable or metastatic biliary carcinoma with MSI-H or dMMR and disease progression during or after at least one prior course of treatment.
• mortality
  • The pharmaceutical manufacturer provides comparisons of individual arms from the KEYNOTE 158 and ABC-06 studies for the endpoints of overall mortality and objective response rate.
• Morbidity – Objective response rate
  • The pharmaceutical manufacturer shall provide comparisons of individual arms of the KEYNOTE 158 and ABC-06 studies for the endpoints of overall mortality and objective response rate.
• Morbidity – Progression-free survival
  • For the endpoints progression-free survival and severe adverse events, the pharmaceutical manufacturer provides a descriptive comparison of the results of 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.
• Conclusion
  • 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, in the present context of a comparison of individual arms, it can be reliably ruled out that they are not solely due to systematic bias caused by confounding factors.
  • Overall, the data presented are not suitable for demonstrating additional benefit compared with the appropriate comparator therapy; consequently, an additional benefit of pembrolizumab as monotherapy is not proven.

Courtesy translation only, please refer to the German original.