Combinations of PD1 and Targeted Therapy

CTLA-4 blockade/ IPPI 

• 10 yr overall survival rate
• 1-3 month duration of treatment 
• 20-30% immune related toxicity 
• Retreat successful 
• Absence of predictive bio-marker 

PD1 Blockade 

• 3-5 yr Overall survival rate
• Superior OS to IPPI 
• DCR >50% Better Kinetics 
• Low immune related Toxicity 
• Up to 2 years continuous treatment 
• Retreat Appears Successful 
• PDL-1 Biomarker Sub Optimal 

Combined CTLA-4 and PD-1 have given results as follows 

• 2-3 years overall survival 60-70%
• 50% PFS plateau at 2 years 
• 1-6 months of treatment rapid Kinetics 
• 50-60% immune related toxicity 
• Retreatment success is unknown 
• PDL-1 marker encouraging 

In the combined treatment it has been proven that PD-1 followed by CTLA-4 sequence is Superior with a 1 yr overall response rate of 76% but with higher grade 3-4  Toxicity in 63%

But early treatment discontinuation does not effect efficacy so the question remains are patients being over treated?

A new era in of immunotherapy by combining therapies means 50% long term survival a reality toxicity management remains crucial and requires teamwork and experience. Toxicity can shorten duration of treatment but does not impare survival! 

The data overall survival rates with Dabrafenib/ Trametnib Combi-d are as follows
3 yrs OS 25% with elevated LDH levels and PFS 13%
3yrs OS 54% with normal LDH levels and PFS 27%
Presentation by Dr Keith Flaherty

Pembro  + IPPi  (Keynote 029) phase 1 153 patients treated
Pembro 2mg in combination with 4 doses of  IPPI 1mg has a manageable toxicity and provides robust anti-tumour activity
ORR was 57%
70% progression free at 6 months at data cut off point
Presentation by  Dr Georgina Long


There is a phase 2 study of Dabrafenib/Trametnib and Pembro combined (Keynote 022)
Recruitment is ongoing