Sunday, 16 October 2016

What cancer drugs will we be taking in 2020?

"What cancer drugs we will take in 2020?"

Quite a fun session too, real science fiction stuff with drones in your blood delivering cytotoxic agents to tumour cells!

Of course we mustn't get carried away, however this does herald the start of a whole range of new approaches in cancer treatment described by one leading oncologist as a tidal wave.

Just think, it was only a few years ago when people were screaming out for access to Ipilimumab which looks pretty ordinary in today's toolkit!

Hopefully the quality of
photos will be better than this in 2020!

Plotting our next moves in ocular melanoma...a very successful meeting!

Ocular melanoma at ESMO has ignited!

Dick & me ran into the Delcath team who may be interested in using the new PUMMA database (released at ASCO which they didn't even know about!) which contains full medical history for 5,000+ OM patients pulled together from previous trials and case series.

The Princess Margaret Hospital in Toronto were instrumental in collating this database alongside an international team of MUM researchers. The result is the first full set of Electronic Health Records (EHRs) spanning 25 years of various case series, trial data and other information from a range of specialist centres in ocular melanoma throughout the World. A true example of collaboration across borders. 

We are now, via the EMA, trying to put this as the surrogate comparator arm in a number of trials. Fingers crossed if this works out we'll start seeing trials with less people on dreadful control arms.

Planning how we work the PUMMA dataset into clinical trials

How to make 'cold' tumours such as metastatic ocular melanoma more immunogenic?

Tony Ribas with a slide showing how we can improve t-cell infiltration on 'cold' tumours (i.e. those with few mutations such as ocular melanoma which consequently perform less well with PD-1 drugs).

The blue dots in the tumour indicate t-cell infiltration.

We can look at techniques such as Adoptive Cell Therapy, CAR T-cells and even targeting tumour escape mechanisms such as the tumour blood supply to make metastatic ocular melanoma tumours more 'immunogenic' (more visible & attractive to the immune system). Fascinating stuff.

Techniques to increase T-cell infiltration for 'cold' tumours such as ocular melanoma

Wednesday, 12 October 2016

(Neo) Adjuvant Ipilimumab plus Nivolumab in Stage 3 Melanoma

Christian Blank, from Netherlands Cancer Institute, and colleagues conducted this two-arm Phase 1b trial consisting of 18 high-risk stage III B/C melanoma patients who had palpable nodes; the median number of lymph nodes involved was 2 (range, 1-4) and 1 (range, 1-5) in the respective arms. The objective response rate (ORR) was 78%. So far, none of the responding patients within the neoadjuvant arm has relapsed.

Ipilimumab plus Nivolumab Adjuvant in Stage 3 Melanoma has a high response rate but comes with considerable side effects (more and more severe side effects in Stage 3 than Stage 4 patients). So Stage 3 Melanoma respond BETTER but have MORE side effects; immune system seems to be suppressed in Stage 4. LBA39 Opacin trial'' Note by Bettina Ryll

More about this research here (posted by Gilly in MPNE forum).

Overview of melanoma drugs

Displayed during poster discussions by Axel Hauschild on 10/10/2016.
photo credit Imogen Cheese

Ipi 10 mg/kg vs ipi 3 mg/kg

Ipi 10 mg/kg showed benefit in overall survival vs ipi 3 mg/kg for the patients with unresectable metastatic melanoma.  At a minimum follow-up of ~43 months, median OS (primary endpoint) was 15.7 months with 10 mg/kg versus 11.5 months with ipi 3 mg/kg. Increased toxicity and no benefit in Progression Free Survival and Overall Response Rate were noticed. Presented by Paolo Ascierto (Abstract 1106O).

photo credit Imogen Cheese

Bettina's comment: 10 mg/kg was already the recommended dose (over 3 mg/kg or 0.3 mg/ kg in the first paper EVER published on Ipi (..) it just happened that the other study with the 3 mg/kg finished earlier and was therefore used for registration: *telling you how we get to the doses we use in the clinic*

Ipilimumab 10 mg/kg vs placebo in adjuvant setting

One of the highlights of #ESMO2016 in melanoma:

A. Eggermont reported the efficacy of adjuvant therapy with ipilimumab in patients with high-risk stage III melanoma after complete lymph-node dissection at a median follow-up of 5.3 years.

Ipi 10 mg/kg showed benefit in overall survival over ipi 3 mg/kg. At a minimum follow-up of ~43 months, median OS (primary endpoint) was 15.7 months with 10 mg/kg versus 11.5 months with ipi 3 mg/kg.

At 5 years, ipilimumab had rates that were approximately 10 %  higher than the rates with placebo: recurrence-free survival (40.8% vs. 30.3%),
overall survival (65.4% vs. 54.4%), and
distant metastasis–free survival (48.3% vs. 38.9%).

However increased toxicity was noticed.  Grade 3 or 4 adverse events occurring in 54.1%. Five patients died due to adverse events of ipilimumab. The results were also published in NEJM on 6 October 2016.