Adjuvant/ neoadjuvant treatment in Melanoma

Neoadjuvant treatment

work in progress please keep coming back


Neoadjuvant = treat, then operate 
Intention: shrink tumour (to make surgery easier or possible) 


Ideal properties of a neoadjuvant treatment would be

• High response rate with predictable kinetics of response (so you know when to expect to see a result)
• tolerability
• Ease of use
• low cost (interesting to see this here right up front on the list)

Quick reminder-

In Stage 3, 5 year OS (overall survival) differs between 93% (IIIA) to 32% (IIID), so treatment options are needed. 

Theoretical Benefits of neoadjuvant

-improve/ allow surgical resection

- treat occult (hidden) metastasis earlier in disease

- assess whether disease responds to treatment

And it MAY

- treatment with immune therapies when tumour antigens are present MAY improve efficacy while reducing toxicity

- it MAY reduce surgery-induced immune-suppression 

Theoretical problems of neoadjuvant therapy

- if treatment doesn't work, progression might make tumour inoperable

- surgery can become more difficult because of local reaction

- patients might drop out (mhm considering that dissection on OS-benefit not convinced about that one)

- can affect later treatment options upon progression (e.g. to participate in a clinical trial)

- toxicity

BRAF/ MEK inhibitors

NOTE- recent Ph3 neo-adjuvant trial was stopped for efficacy of the experimental arm. 

Amaria 2018 (Lancet) 

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30015-9/fulltext

Checkpoints neo-adjuvant

Ipi- relatively low response rate with relatively high toxicity

PD1- response rate ok, low toxicity

Ipi plus Nivo- high response rate, high toxicity

T-Vec

• response rate 26- 33%, seems higher in transit mets than in nodal disease
• Grade 3/4 toxicity - 2% 
• not that easy to handle and patient has to come back every 2 weeks

Isolated limb infusion/ perfusion

high response rate 50- 80%
hospital admission, toxicity moderate (mhmm)
Considered for localised disease as treatment confined to affected limb



Georgina Long

Rationale of adjuvant vs neoadjuvant therapy

Lo, S Annals Surg Onc 2018
Stage 1 Melanoma OS

shows 20 year OS in even early stage Melanoma drops- READ


Neoadjuvant

single dose of PD1 neoadjuvant, than surgery
patients who achieve a complete pathological response do not tend to recurr


Adjuvant vs neoadjuvant
Rozeman ESMO2017
Differences in T-Cells mounting response between neoadjuvant vs adjuvant- more diversity when treating neoadjuvant

and again
PDL1 should NOT be used to direct anti-PD1 treatment- data to come on Monday


Best slide of this morning :-)