Week 107 and 108: Most interesting research presented at ESMO

Written by Lars Haakon Soraas
15
Sep

Week 107 and 108 in the war on cancer has passed. Dyanne had a CT scan this week and she will on Monday have an MR scan. We will learn results from these next week. In general: Dyanne is in good shape.

I was at the CIMT meeting in Mainz, Germany last week. I hope to be able to write up some of the highlights from that conference. However, I have spent most of the last few days looking at the data coming out of the ESMO congress which was taking place in Madrid over the weekend. ESMO is one of the largest gatherings of cancer researchers worldwide and takes place once a year. In case it can be of interest for other patients, I will in this blog post summarize some of the research presented at the conference that I find the most interesting. I have put all posters and presentations that are mentioned in this blog post in this dropbox folder:

https://www.dropbox.com/sh/tbgr9f2eozbayn0/AACNtHfQUik1hcv2x6MsGz2La?dl=0

The folder also contains some posters and presentations not mentioned in this blog post. And when commenting on the various posters and presentations below, I have tried to link directly to the relevant files in the dropbox folder.

Most interesting posters

1. Impact on OS and PFS of 2nd and 3rd generation TKI in EGFR mt+ and ALK+ pts – Results of the NOWEL network: this poster indicates that patients who got both a first line and a third line (i.e. osimertinib) EGFR TKI, had a median survival of 67 months! Small sample, and retrospective study, but nevertheless encouraging data 🙂

2. Overall survival (OS) in patients (pts) with EGFR T790M-positive advanced non small cell lung cancer (NSCLC) treated with osimertinib – results from two Phase II studies: some survival data from the trials which have tested osimertinib as a second line treatment. Median survival for these patients were almost 27 months. On top of this should be added the time on previous treatments that these patients had before they started on osimertinib. I think that adding a year is conservative (many patients had 2 or more lines of treatments before they started the osimertinib trials). This means the median survival of these patients, from the time of diagnosis, probably was around 40 months. Not good enough, but seems to be an improvement compared to older data for patients who only got one EGFR TKI and then chemo (typical survival from these studies have been 25-30 months).

3. Subsequent therapies post-afatinib among patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC in LUX-Lung (LL) 3, 6 and 7: a very interesting poster by Lecia Sequist and others. It shows that patients who got afatinib as first line treatment, and then osimertinib later, had a very long duration of response to osimertinib: median of 20 months! The median survival for these patients has not yet been reached, but the 25th percentile is 59 months! The median (50th percentile) is probably then significantly more than this. Also very encouraging data!

4. Effect of silibinin nutraceutical supplementation in brain metastases of patients with advanced lung cancer: very promising for a simple nutraceutical – seems like this simple nutraceutical can help battle brain mets. Can be bought over the counter in Spain and maybe also some other countries.

5. Efficacy and Immune Activation with PEGylated human IL-10 (AM0010) in Combination with an anti-PD1 in Advanced NSCLC – Update: this AM0010 seems like a promising treatment, especially in combination with anti-PD1. The trial is here: https://clinicaltrials.gov/ct2/show/NCT02009449. But it is, unfortunately, not recruiting at this point in time.

6. Prominent immune suppressive tumor microenvironment in female never-smoker lung cancer patients with EGFR mutations: this is an interesting poster which shows that the tumor microenvironment for EGFR positive patients has special characteristics which probably impacts the efficacy of immunotherapy. I am not an expert, so don’t know how one can use this to optimize the immunotherapy we and others are trying.

Most interesting presentations

1. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC – FLAURA: a much anticipated presentation about osimertinib in first line. Encouraging results (PFS with osimertinib was 19 months vs 10 months with erlotinib/gefitinib). However, the data does not, in mind, prove that it is better to get osimertinib as first line treatment than e.g. erlotinib/gefitinib/afatinib and then followed by osimertinib (at least for those with T790M). I know some oncologists on twitter were very positive. But I am a bit less convinced. With the hefty price tag, I doubt osimertinib will be implemented as first line treatment in Norway anytime soon. We will see.

2. The Winner Takes It All – Tony Mok discussion of Flaura results: Tony Mok had a good discussion of the Flaura data. His conclusion is that patients with brain metastasis should get osimertinib rather than other EGFR TKIs as front line treatment. This may be right. Don’t know. In any case, I would be in favour of upfront stereotactic radiation of any brain mets as well.

3. Oligometastatic NSCLC – Management of oligometastasis in patients with driver oncogenes – Sequist: a nice presentation which indicates the value of local ablative treatment, perhaps even upfront rather than at resistance. She mentions a trial at MGH in Boston which adventurous patients presumably should be able to replicate if their local doctors cooperate: A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC (https://clinicaltrials.gov/ct2/show/NCT02314364).

4. Brain progression on targeted therapies and immunotherapies – The medical oncology perspective – Sequist: This is a good presentation on the management of brain progression in NSCLC patients.

5. Challenges in oncogene addicted NSCLC – The role of immunotherapy in oncogene addicted NSCLC – Peters: Solange Peters had this very good presentation about the role of immunotherapy in EGFR positive patients. Everyone with EGFR positive lung cancer should read this, both those on immunotherapy, and those considering it in the future (hence: everyone).

6. Challenges in oncogene addicted NSCLC – Strategies against mechanisms of resistance – Jänne: Pasi Jänne of Harvard had this, in my opinion, rather depressing presentation. Depressing because it can pretty much be summarized as: “We don’t really have any good strategies for overcoming resistance…”. I do hope the research community will use the insights coming from researchers like Robert Gatenby, Ivana Bozic and Christina Curtis (for the two latter, see presentations below) and come up with better strategies for how to beat this disease.

7. Challenges in oncogene addicted NSCLC – New drivers, new perspectives – Mok: A nice presentation by Tony Mok. A good overview over everything that is not EGFR or ALK, but still relevant for us as we may get these mutations/alterations/amplifications as resistance mechanisms.

8. Cancer evolution and metastasis – Phylogenetic modeling of cancer cell populations – Bozic: While most researchers in EGFR mutant lung cancer keep pursuing strategies we know will not work, people like Bozic does the math and give valuable insights into what it will take to cure this disease. Here are the hard truths: a 1 cm3 lesion probably contains around 1000 resistant cells before even starting therapy. If you have, like Dyanne, a 3 cm3 lesion and many small ones as well, you can probably multiply by 20 (i.e. 20 000 resistant cells). Another interesting number is this: A 1 cm3 lesion probably contains 10 resistant subclones – before the start of therapy. Even if these numbers are, of course, just rough estimates, they nevertheless shows the futility of the strategies that most oncologists working on solid tumors (such as lung cancer) are pursuing. And, in my mind, these data do indicate one of the benefits of local treatment: not only do you get rid of cancer cells, but you reduce heterogeneity by getgting rid of resistant subclones . I very much encourage everyone to read her presentation.

9. Cancer evolution and metastasis – Quantifying the evolutionary dynamics of tumor growth and metastasis – Curtis: this is also an interesting presentation, even if it mostly focuses on colon cancer. It may be a bit hard to read, so if you can access the video fo the presentation (become a member of ESMO and you will have access), that may be better.

Those were, at least in my opinion, some of the most interesting presentations and posters from ESMO – at least for EGFR positive lung cancer patients.

Have a good weekend everyone!

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