Wednesday, 15 June 2016

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 

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