One area that is finally seeing a lot more research results of late is neo-adjuvant therapy in breast cancer, i.e. therapeutic intervention prior to surgery.
The main advantages of neo-adjuvant over adjuvant therapy are:
- If it works, then the therapy allows the margins to shrink prior to surgery, potentially making the tumour easier to excise
- If therapy works prior to surgery, you know what will likely be effective post surgery, whereas in adjuvant treatment after surgery, this is unknown.
One of the leading trials for neoadjuvant breast cancer was the ISPY2 (Investigation of Serial studies to Predict Your therapeutic response with imaging and molecular analysis 2) study. I wrote about it in more detail at the time it was launched on Pharma Strategy Blog, if you need more information. Basically, the study is based on a complex adaptive conjoint design in neoadjuvant breast cancer, so over time, additional arms were added to the study (there were originally four) while others were removed. In this way, the investigators can find the best therapies for each tumour subtype (HER2+/1, ER+/- or triple negative) based on the responses and biomarkers.
One element of neoadjuvant trials is figuring out what the most valid and meaningful endpoints are. In metastatic breast cancer (MBC), for example, we tend to see the primary and secondary endpoints being focused around the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). These endpoints are rarely used in neoadjuvant trials though, because:
a) the goals of therapy are different and
b) patients are expected to live much longer with earlier stage disease so other outcomes such as DFS or EFS are often used
Given these factors, the FDA recently brought out new guidelines suggesting that pCR improvement would be a useful surrogate marker and predictor of survival endpoints. One example they used was HER2 disease and the ISPY2 model where drugs ‘graduate’ based on their performance over time. This is why the current ISPY2 trial is recruiting different arms than the original study setup. The first two therapies were considered to have ‘graduated’ from the trial with data (triggered 60–120 patients are enrolled) late 2013, i.e. AbbVie’s veliparib, a PARP inhibitor, and Puma’s neratinib, a pan-HER/ErbB inhibitor.
Veliparib was considered to have graduated in the triple negative signature. Initial veliparib data was presented at SABCS in December (see our analysis, commentary and update of this study data here). The neratinib data has yet to be presented at a medical conference, although the company have announced an oral presentation at AACR in 3 weeks time.
That said, neratinib and neoadjuvant therapy, in general, was discussed by several participants at last week’s Miami Breast Cancer Conference (MBCC).
For those interested in my thoughts and analysis, you can sign in or sign up below:
Following on from yesterday’s update on how proteomics and genomics can help us make better decisions in breast cancer at the Miami Breast Cancer Conference (#MBCC14) organised by PER, today also looks at the complexity of genomics, but from a different lens – can genomics impact the way we actually treat patients?
Interestingly, last week there was a rumour (unconfirmed) that Dr Debu Tripathy (UCLA) was heading to MD Anderson to head up the breast cancer division following Gabriel Hortobaygi’s retirement. That move was confirmed yesterday, with a tweet from Dr Naoto Ueno, who is part of the group:
His talk on the increasing role of genomics in breast cancer on Friday was engaging, thoughtful and well delivered.
It also made me (and several others) stop and think.
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On Friday, I headed uptown to attend the Miami Breast Cancer Conference (#MBCC14) held at the Fontainebleau Hotel and organised by the Physicians Education Resource (PER). It was fun to grab a local Deco Bike and furiously cycle over 45 blocks in under half an hour – most probably the only attendee who arrived on two wheels that day!
MBCC14: Dr Lance Liotta
Now, I haven’t attended this event since it was at the Loews Hotel in midtown, which was rather low key and fairly small. Certainly there wasn’t a big exhibition area then, as far I can recall. Fast forward a decade on and the event is MUCH bigger, with an excellent Academic panel and an interesting mix of didactic talks and case studies. The stage setting is also much more impressive, as you can see in the photo right.
To give you some basic background, the audience polls at the beginning of the first day were really useful to put things into context:
- The majority of attendees (88%) were physicians (mix of Community medical oncologists, radiation oncologists and surgical oncologists)
- 49% of respondents treated 1–5 patients with breast cancer per week
- 25% of respondents treated 6–10 patients with breast cancer per week
Being a scientist, and having missed the San Antonio Breast Cancer Symposium (SABCS) due to an overlap with the American Society of Hematology (ASH) meeting in December, I was particularly keen to catch up on the new developments in genomics and molecular profiling, with early morning talks from Drs Lance Liotta (George Mason Univ) and Debu Tripathy (USC). There were also updates on neoadjuvant treatment for breast cancer by Drs Kathy Albain (Loyola) and Hal Burstein (Dana Farber). Neoadjuvant therapy prior to surgery is an area that is seeing many new trials and potential therapies emerge.
In today’s post, the attention is on the important topic molecular profiling. This is something I believe we will see much more of going forward. Two separate articles will follow on personalised treatment in advanced breast cancer (including TNBC) and also on neoadjuvant developments.
Genomics can sometimes be a bit of a dry topic, at least to some people, as anyone who has sat through slide after slide of those fuzzy green-red assays in systems biology sessions at AACR will attest. This time, much to my pleasant surprise, it was different…
What I heard blew my mind and changed the way I think about some aspects of breast cancer.
Now I’m not joking or trying to hype progress here, but sometimes you experience an epiphany when you least expect it.
To read more about this revelation, you can sign up or sign in below.