Looping across different types of analyses can yield intriguing and unexpected results
Not in Chicago – It still feels surreal not to have been to windy city and back for the annual meeting at ASCO this year, such was the ongoing effect of the pandemic in the oncology world.
That said, the virtual meeting has produced some gems this year, including some very important findings many may have missed.
In our latest post meeting report we focus on both biomarkers and clinical findings.
We look at how there are various elements may interplay in unexpected ways, whether signatures from one trial are helpful in another, are there likely to be changes in treatment patterns as a result of data presented and where some emerging early signals might be useful.
One other aspect which crossed my mind was how a deep scientific approach used in one particular cancer might have potential applications in other tumour types with few somatic mutations present such as TNBC, prostate cancer or soft tissue sarcomas.
The results might produce quite different results, yet the process itself might be rather useful to consider…
To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the ASCO meeting, subscribers can log-in or you can click to gain access to BSB Premium Content.
Embedded deep in any conference database of abstracts are often important findings, which tend to be overlooked by many observers in the rush to focus on the more obvious candidates.
Time to scale the cliff on a previously little known and undruggable target!
This preview and accompanying thought leader interview explores one such underrated avenue of research.
There is a lot to be said when we have clear signals from our knowledge of the underlying biology in front of us because they inform where therapeutic intervention should be both rational and fruitful.
Is this actually the case in practice?
We dug deeper to find out what’s really happening…
To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the ASCO meeting together with our latest KOL interview, subscribers can log-in or you can click to gain access to BSB Premium Content.
We’ll have “boots on the ground” for the 2018 Congress of the European Society for Medical Oncology (Twitter: #ESMO18) that starts out of the gate on Friday in Munich.
The Fall cancer conference season is in swing…
Our conference coverage is not only about what data we think matters, particularly in the fast-moving world of immuno-oncology, but more importantly, why it matters.
Next up in our ESMO18 Previews, we take a closer look at renal cancer, an area that received some attention in Madrid last year and is likely to receive renewed focus again.
We also include a look at the broader RCC landscape in terms of US physician prescribing habits (i.e. KOL and Community oncologists), including some trend data to explore the impact of the nivo/ipi combination and cabozantinib data, as well as excerpts from an expert interview we conducted with Dr Awny Farajallah, Head of U.S. Medical at Bristol Myers Squibb.
Finally, we also highlight some key abstracts to watch out for in renal cell carcinoma (RCC) that are expected to be presented at ESMO18 and explore their relevance.
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For what seems the longest time, we have seen the battle in metastatic clear cell renal cell carcinoma (ccRCC) being focused on various anti-VEGF TKIs, whether against interferon, mTOR inhibitors, and even each other.
Lately, anti-PD(L)1 antibodies have also come on the scene – both as monotherapy and in different combinations – so are things set to change?
Will it be plaining sailing or are there hidden dangers ahead for the unwary?
Here, we take a look at the ever evolving landscape in RCC and explore the issues and challenges surrounding some of the novel combination readouts, including a look at the role immuno-oncology might play going forward.
Not surprisingly, there’s a lot to consider, discuss and think about…
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At the inaugural event in Orlando last year, one of the highlights for me was learning how important CD38 might turn out to be as another immune checkpoint target in combination with other approaches.
This year the meeting moved to the west coast and was held in San Francisco, making it the third one this month after JPM18 and GI18. Indeed, the fourth such event is also rapidly coming up with ASCO GU next month!
So what did we learn this time around? Quite a lot it would seem.
While much of the clinical data of late associated with immune checkpoint blockade (ICB) has been in metastatic melanoma and non-small cell lung cancer (NSCLC), two other tumour types that have received increasing attention in the IO space have been clear cell renal carcinoma (ccRCC) and prostate cancer.
There were a few interesting new things we can learn here…
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There’s been another disturbance in the force – as luck would have it, after mentioning renal cell carcinoma (RCC) in yesterday’s post, BMS subsequently put out a press release on the CheckMate–214 study exploring the combination of nivolumab plus ipilimumab in the previously untreated metastatic setting.
The results to date were mixed, so what does this mean and what’s impacted by the findings?
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Today for the second AACR 2017 Preview, I wanted to switch things up a bit and turn from looking at an important trend to a specific tumour type. One of the reasons for this is that we received questions from readers about recent data presented at medical meetings in this sphere.
It’s also not something that we have covered extensively here on BSB, so looking at something in a different light is often a good idea since insights and intelligence can sometimes jump out afresh.
Given that there are also some important clinical trial results emerging here, this is something we can expect to return to in Washington DC when the data is presented at AACR next month. What can we learn ahead of the event though? It turns out the answer is quite a lot.
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New developments in renal cell carcinoma
Continuing our focus on genitourinary (GU) cancers this week, today we turn our focus from prostate cancer to renal cell carcinoma (RCC).
There were two important announcments on Monday this week relating to renal carcinoma.
Firstly, Exelixis announced positive top line data from a phase 3 pivotal trial of cabozantinib versus everolimus in relapsed metastatic renal cell carcinoma (METEOR). The study met the primary endpoint (i.e. significantly improved progression free survival) and the company revealed the following data:
- Cabozantinib reduced the risk of disease progression or death by 42%; Hazard Ratio = 0.58, (p < 0.0001) compared to everolimus
- Interim Analysis of OS demonstrated a trend in favour of cabozantinib; Hazard Ratio = 0.67, (p = 0.005) compared to everolimus
- Exelixis to complete US and EU regulatory filings in early 2016
Secondly, a press release from BMS highlighted the phase 3 CHECKMATE–025 trial comparing nivolumab to everolimus, also in relapsed metastatic RCC, where the independent Data Monitoring Committee recommended early stoppage on the basis of the primary endpoint (OS) being met. The company likely be seeking discussions with Health Authorities with a view to filing the data with the FDA and EMA.
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At the last count, the renal cell carcinoma (RCC) space is quite competitive with five VEGF inhibitors (sunitinib, sorafenib, axitinib, pazopanib and bevacizumab), two mTOR blockers (temsirolimus and everolimus) and not forgetting IL–2, all approved by the FDA for the treatment of advanced disease.
Much of the recent focus has been on sequencing, exploring combinations (generally too toxic with little added benefit), and evaluating the potential for novel immunotherapies in development such as checkpoint inhibitors. Biomarkers are few and far between, making it hard to rationally decide which therapy each patient should get and in which sequence.
The key question is, why is this tumour type so challenging from a clinical and scientific perspective?
Recently, new data has begun to emerge that may help inform or enable us to switch to new approaches. While the urologists are eagerly watching the live surgery on the EAU cam, we highlight research data presented at the European Association of Urology (EAU) in Madrid and take a look at how the underlying biology of RCC can elevate our knowledge about where the potential future strategies and blueprint might lie, if we want to facilitate exciting new developments in this field.
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In her ASCO Gastrointestinal Cancer symposium (ASCO GI) keynote presentation earlier this year, Elizabeth M. Jaffee MD described the future of immunotherapy as being in combinations.
Overcoming or delaying resistance mechanisms or hitting multiple targets to greater effect will be achieved through combinations of drugs rather than single agent therapy. Combination strategies are the accepted future, whether drug companies like it or not.
In her keynote, Dr Jaffee also likened the revolution in immunotherapy to the same excitement the Beatles brought to music or the same magnitude of technology advances made by Apple. We agree completely.
Thought leaders at ASCO expressed similar sentiments. Steven O’Day (UCLA) said,
“This is truly a brave new world of immunotherapy. I think the message is that the revolution is here, it’s ongoing, and it’s bursting out of melanoma into solid tumors.”
Interestingly, no immunotherapy data was considered to be of worthy of presentation in the plenary session at ASCO this year for the second year running, a decision that may reflect either an unwillingness to showcase early data, however good it may appear to be, or the influence of politics on the selection committee.
One potential combination is to target more than one checkpoint pathway to see if you can obtain a synergistic response. This is the rational for combining the monoclonal antibody ipilimumab and nivolumab. Ipilimumab (Yervoy) targets the CTLA-4 checkpoint protein that prevents dendritic cells from priming T cells to recognize tumors while nivolumab targets the PD-1 checkpoint protein that prevents T cells from attacking cancer cells. Yervoy is an FDA approved therapy for the treatment of metastatic melanoma.
Data published last year in The New England Journal of Medicine by Wolchok et al, showed that combining ‘ipi’ with ‘nivo’ gave more frequent and deeper responses in melanoma, but at the expense of much greater toxicity. Some 53% of patients receiving concurrent treatment had a grade 3-4 adverse event (see Table S-1B in the article).
Does it make sense to combine two immune pathway modulating agents? Does the enormous potential for synergy outweigh the additional toxicity?
To learn more about these insights, log-in for our analysis of the data on nivolumab in renal cell carcinoma (RCC) presented at ASCO 2014.