Thursday, 25 October 2018
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
58% OS Ipi/ Nivo at 3 years in skin Melanoma- highest ever survival in Melanoma
- primary resistance about 30%
- rarer subgroups of Melanoma
UM median OS 9- 12 months in stage 4
mPFS= 2.6 months
seems to have low PDL1 overall
GEM1402: Ipi + Nivo standard scheme in UM
PFS 2.78 months
OS 56% at 1 year and very few patients at end of curve- so not trustworthy
overall disappointing :-(
19 patients only
68% OS at 1 year
Nivo low plus Ipi vs Nivo plus Ipi low
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
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
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
Why treating early stage patients?
Early stage patients have all the favourable disease outcomes that we know from Stage 4
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)
neo-adjuvant seems better than adjuvant- and patients do not relapse
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
'test your favourite combinations in neo-adjuvant' NAHHHH
and you will chose the *most promising* option, so time for research!
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
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
IO combinations: Nivo with Ipi low/ T-Vec
Fake News and Pseudoscience are dangerous for patients. So very pleased and incredibly proud to see Gilly's session covered on the ...
Why treating early stage patients? Early stage patients have all the favourable disease outcomes that we know from Stage 4 cancer immu...
Also this year- updates from ESMO! The program is available online here
Rotterdam criteria Again- tumorload below 0.1 equals no tumour load in the sentinel node in Stage 3A- check out the Rotterdam criteria ...