A short, but quite important, post today highlighting an early target we are keen to follow in terms of combination trials in both GI and GU cancers, as well as others.
There’s been a lot of focus this year on the so-called inflamed (hot) and non-inflamed (cold) tumours, but what about the intermediate ones that many refer to as the immune excluded phenotype?
View of Geneva from Cathedral St Pierre, Switzerland
Clearly it makes sense to consider different combination approaches in each category, but what would be appropriate? Before we can set about doing that, we first have to uncover the mechanisms causing the inhibition on the tumour microenvironment and then figure out how best to identify those patients most likely to benefit.
Over the last couple of years, we’ve seen and written a lot about various potential candidates (not all will be useful), including myeloid derived suppressor cells (MDSCs), regulatory T cells (Tregs), tumour associated macrophages (TAMs), chemokines, cytokines, adenosine fog and many others.
There is one target that has started gathering a little bit steam over the last year that we have mentioned a couple of times on BSB and now there is something new to discuss here, at least from a big picture perspective.
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We’re overdue a roundup and discussion on various key topics of interest to BSB readers, so here goes…
Today’s topics include an in-depth look at the impact of some negative events:
- Kite and the cerebral oedema death with axi-cel
- Genentech’s atezolizumab OS miss in urothelial cancer
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National Harbor, MD
Bladder cancer is the most common of the urothelial cancers and is the 9th most common cancer globally, with over 400,000 new cases each year and around 165,000 deaths. In the US, approximately 76,000 Americans will be diagnosed with bladder cancer in 2016 and ~11% of new diagnoses are made when bladder cancer is in advanced stages.
Unlike tumour types such as ovarian and pancreatic cancers, the majority of bladder and urothelial cancers are diagnosed at an earlier stage. The rates of recurrence and disease progression, however, are high and approx. 78% will recur within 5 years while the 5-year survival for stage IV bladder cancer is pretty dismal at 15%.
Earlier this year, Genentech/Roche’s anti-PDL1 antibody atezolizumab (Tecentriq) was approved by the FDA in the second line setting and was the first such new approval in this disease for 30 years.
Since then, there has been heightened interest in urothelial and bladder cancers in multiple settings, with several companies rushing to play catch up, including Merck and BMS.
We’ve been following the steady progress of checkpoint blockade this year at AACR, ASCO, ESMO and now SITC – amazingly, what was once a graveyard for Pharmaland has now become a hypercompetitive niche in a very short time.
Here, we take a look at the latest data in advanced urothelial cancers and explore the landscape in the context of rapidly increasing competition.
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Copenhagen – it’s the end of Day 2 of the European Society for Medical Oncology (ESMO), which this year had a record-breaking 20,239 attendees.
Three of the presentations in today’s plenary Presidential Symposium were simultaneously published in The New England Journal of Medicine – I haven’t seen that happen before.
All three were also featured in this morning’s media briefing in Copenhagen.
- Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer (NEJM link)
- Prolonged Survival in Stage III Melanoma with ipilimumab Adjuvant Therapy (NEJM link)
- Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer (NEJM link)
In today’s daily digest there’s top-line commentary and insights from some of the sessions we attended. In a separate post, we have already discussed the niraparib data.
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Following on from yesterday’s post on the potential for small basket trials in ER+ breast cancer with the ESR1 mutation, I wanted to highlight another area where these type of highly focused and rational studies appear to be not only useful but also potentially produce stunning responses.
Some of you will recall the fascinating and widely told story of a single bladder cancer patient at Memorial Sloan Kettering who was resistant to multiple lines of therapies. The team sequenced the genome and found a rare TSC1 mutation. Importantly, this is known from pediatric astrocytoma studies, to be sensitive to an mTOR inhibitor, everolimus (Afinitor). The refractory patient was given the drug and responded well. The rest is history, as they say.
Can we learn more from these type of appraches, i.e. genomic sequencing of patients who have relapsed after initial therapy?
Can we also learn more from the few exceptional responders in clinical trials – what was unique about their response that elicited such a stunning effect?
The short answer is a resounding yes.
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