Table 43. Cross study comparison of the safety profiles of pembrolizumab and BRAF + MEK inhibition P006 P001 P002 COMBI-D COMBI-V [18 (interim April data) arm) arm) data) 2014; 2 mg/kg Q3W] 7 to 11% 10% 9% 13% due to 11% AEs Severe AEs 43% 47% 35% 52% Top 5 AEs not fatigue fatigue pyrexia pyrexia (43%), (39%), (51%), (53%), nausea pruritus fatigue nausea (32%), (25%), (35%), (35%), headache diarrhoea (30%), (21%), (30%), (32%), chills diarrhoea nausea (31%), (21%), (30%), chills vomiting (28%), nausea (30%) (29%) pruritus (20%) and rash (26%) For BRAF monotherapy, discontinuation due to AEs was reported in 5% (COMBI-D) and 12% (COMBI-V); and severe AEs in 37% (COMBI-D) and 63% (COMBI-V). Other comparisons Summary data from P002 are useful in the comparison of pembrolizumab and chemo. Differences in exposure across arms and the mix of control chemotherapies make head to head comparisons difficult, but pembrolizumab’s safety profile seems very different and relatively good (especially for the 2 mg/kg arm). Other Viral infection PD-1’s role in human biology is not limited to the maintenance of tolerance. It regulates antibody responses and the response to viruses (as well as tumours). Some plausible effects related to these roles were not well-examined. For example, in HCV positive patients, it would have been useful to search for any evidence of altered control of the infection. There were cases of elevated LFTs and / or hepatitis, but no attempt to relate these cases to a history of HCV or HBV. It is possible that blockade of PD-1 PD-L – signalling might trigger immunopathology as previously exhausted virus-specific T cells are reactivated. The FDA Summary Review states:
Table 43. Cross study comparison of the safety profiles of pembrolizumab and BRAF + MEK inhibition P006 data) P001 [18 April 2014; 2 mg/kg Q3W] P002 (interim data) COMBI-D arm) COMBI-V arm) due to AEs 7 to 11% 11% 10% 9% 13% Severe AEs 43% 47% 35% 52% Top 5 AEs not fatigue (43%), nausea (32%), (30%), (28%), pruritus and rash (26%) fatigue (39%), pruritus (25%), (21%), diarrhoea (21%), nausea (20%) pyrexia (51%), fatigue (35%), headache (30%), nausea (30%), chills (30%) pyrexia (53%), nausea (35%), diarrhoea (32%), chills (31%), vomiting (29%) For BRAF monotherapy, discontinuation due to AEs was reported in 5% (COMBI-D) and 12% (COMBI-V); and severe AEs in 37% (COMBI-D) and 63% (COMBI-V). Other comparisons Summary data from P002 are useful in the comparison of pembrolizumab and chemo. Differences in exposure across arms and the mix of control chemotherapies make head to head comparisons difficult, but pembrolizumab’s safety profile seems very different and relatively good (especially for the 2 mg/kg arm). Other Viral infection PD-1’s role in human biology is not limited to the maintenance of tolerance. It regulates antibody responses and the response to viruses (as well as tumours). Some plausible effects related to these roles were not well-examined. For example, in HCV positive patients, it would have been useful to search for any evidence of altered control of the infection. There were cases of elevated LFTs and / or hepatitis, but no attempt to relate these cases to a history of HCV or HBV. It is possible that blockade of PD-1 – PD-L signalling might trigger immunopathology as previously exhausted virus-specific T cells are reactivated. The FDA Summary Review states:
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