Thursday, 25 October 2018

ESMO 2018 Congress TV: Protecting Patients from Fake News with Gilliosa ...

Fake News and Pseudoscience are dangerous for patients. 
So very pleased and incredibly proud to see Gilly's session covered on the ESMO congress TV!

Saturday, 20 October 2018

Ipi Nivo combos- what's new? G. Long

Uveal Melanoma

58% OS Ipi/ Nivo at 3 years in skin Melanoma- highest ever survival in Melanoma

  • primary resistance about 30%
  • toxicity
  • rarer subgroups of Melanoma

UM median OS 9- 12 months in stage 4

PD1 mono 
ORR 3.6% 
mPFS= 2.6 months

seems to have low PDL1 overall

GEM1402: Ipi + Nivo standard scheme in UM

ORR 11.5%
PFS 2.78 months
OS 56% at 1 year and very few patients at end of curve- so not trustworthy

overall disappointing :-(

IMCgp100- 102 

19 patients only

68% OS at 1 year


Nivo low plus Ipi         vs       Nivo plus Ipi low

endpoints: toxicity
not powered for ORR, PFS and OS    *sigh*

and let's pretend we're surprised: more Ipi is more toxic 
and there more discontinuations.....

really- hard to see what this trial was supposed to answer 

Intra-tumoural injections- poster discussions

1. SD101- Tol9 receptor agonist plus PD1 in - not sure why you would do that- PD1 naive patients

data for PDL1 status needs to be verified as inconsistent

Interesting bit in here is that seems that the higher dose works less well than the lower dose

check poster

2. TLR9-agonister (Tilosotolimod) IMO-2125 plus Ipi in PD1 refractory patients, so the ones who failed PD1 treatment

response in injected and also in un-injected lesions

look into which T-cells clones expanded

3. T-Vec in IIIB-IVM1c patients 

biopsies at baseline and day1 of week 6- looking at CD8+ density

no correlate between density and objective response but durable response (objective response >6 months)

change in density didn't correlate with either


but- they change of CD8+ was seen also in uninjected lesions, so there IS a systemic effect of the T-Vec

4. Pembro plus Dab/Tram intermittendly- IMPEMBRA

small numbers, so caution

Hardly novel trial reasoning- better responses early on targeted therapy than on immune therapy- but different lengths of treatment with Dab/Tram 

but seems that the Dab/Tram combination creates a favourable environment for immune therapy READ UP

Neoadjuvant treatments by Christian Blank

Why treating early stage patients?

Early stage patients have all the favourable disease outcomes that we know from Stage 4

cancer immunogram

Why treating neoadjuvant

1. we know whether therapy was effective
2. we can reduce tumour burden very fast- easier surgery
3. we can use pathological response as an outcome parameter
4. in case of checkpoint- inhibitors induces a broader and deeper expansion of T-cell clones
5. easier baseline biomarker identification 

pure neo-adjuvant with 12 weeks: still relapses, so not the way to go
(Georgina Long's work)

Opacin trial

neo-adjuvant seems better than adjuvant- and patients do not relapse

get slides

Problem: very high toxicity

and PD1 monotherapy neo-adjuvant considerably lower response rate when compared to Ipi plus Nivo

also longer treatment with PD1 not successful

so which way to go?

OPACIN- neo trial- late breaker on Monday

lower ipi dose in combination
altered admin scheme

Personalised immunotherapy

'test your favourite combinations in neo-adjuvant' NAHHHH
and you will chose the *most promising* option, so time for research!

Lex Eggermont- outlook for Stage 3 Melanoma

Rotterdam criteria

Again- tumorload below 0.1 equals no tumour load in the sentinel node in Stage 3A- check out the Rotterdam criteria
Reported in detail at ASCO this year 

Important note-

when we look at OS data from adjuvant treatment, this is a combined result from the adjuvant treatment plus any following therapy

and there is no gain possible- so missed adjuvant, you cannot recover in the metastatic session

There will be an update on the PD1 adjuvant OS by Georgina Long on Monday morning

OS curves from adjuvant Melanoma between targeted therapy and immune therapy appear to cross at about 2 years

'The end of Interferon (in the rich world) but then- he DOES find a use for his Interferon....but please *just* for the ulcerated primaries due to different disease biology

Check out Danielle Verver's publications- there are alternatives to identify the prognosis than CLND

What next?

Duration treatment?
IO combinations: Nivo with Ipi low/ T-Vec

get slides

Welcome to the MPNE at ESMO 2018 blog

Also this year- updates from ESMO!

The program is available online here

ESMO 2018 Congress TV: Protecting Patients from Fake News with Gilliosa ...

Fake News and Pseudoscience are dangerous for patients.  So very pleased and incredibly proud to see Gilly's session covered on the ...