In this episode of Novel Targets, we take a broad look at a range of new data that has been emerging for the treatment of breast cancer from several recent cancer meetings, and hear from experts who are shaping the future.
1. The Metastatic Breast Cancer Project
Not all studies are company sponsored. Some of them are driven by academics and may involve patients in novel and collaborative ways. Suppose you happen to be a person with metastatic breast cancer… you could have the power to accelerate cancer research in a way that no one else can, as we found in an compelling and candid interview with Dana Farber’s Dr Nikhil Wagle.
He established the Metastatic Breast Cancer Project (mbcproject.org) as a way to collaborate with patients and enable curation of their tumour samples and medical history such that researchers could then datamine the information and share the results with the MBC community.
Dr Wagle explains the kind of information he hopes will evolve from this important and groundbreaking project.
2. PARP inhibition in Metastatic Breast Cancer
PARP inhibitors have been very much one of the hottest topics in cancer research of late.
In episode 15, for example, we highlighted how these targeted drugs are changing the treatment of ovarian cancer. What about breast cancer though? At ASCO, we heard new data from a phase III trial in HR- breast cancer in people with germline BRCA mutations (olympiAD), which made one of the prestigious four plenary slots at the American Society of Clinical Oncology (ASCO).
This study compared olaparib to chemotherapy and was the first late stage trial to demonstrate a significant benefit in favour of a PARP inhibitor in metastatic breast cancer. The data was presented by Dr Mark Robson (Memorial Sloan Kettering, NY) and simultaneously published in The New England Journal of Medicine (Link).
So what did experts have to say about this important data and where are things going next?
In this segment, we interviewed a range of scientists and researchers from around the world, including Drs Sherene Loi @LoiSher (Peter MacCallum, Melbourne), Eric Winer (Dana Farber), Johnathan Lancaster (Myriad), Mark O’Connor (AstraZeneca), Gordon Mills (MD Anderson, now OHSU) and Peter Schmid (Barts, London), to learn more about their different perspectives and reactions to the data.
3. Targeting HER2/HER3 in Adjuvant Breast Cancer
Over a decade ago, the addition of trastuzumab to chemotherapy became the standard of care for the treatment of HER2+ breast cancer in the adjuvant setting. Subsequently, on September 30, 2013, the FDA granted accelerated approval to pertuzumab in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive breast cancer.
The obvious next question is what happens when pertuzumab is added to trastuzumab plus chemotherapy in the adjuvant setting?
Last month at ASCO we found out what the outcome of this combination was when the much anticipated phase 3 APHINITY trial was finally presented in an oral session by Dr Gunter von Minckwitz (German Breast Group) and also simultaneously published in the NEJM (Link).
In this show we hear candid reactions to the data from breast cancer experts, including Drs Eric Winer (Dana Farber, Boston) and Sherene Loi (Peter MacCallum, Melbourne).
They take us through the key nuances and subtleties associated with the interpretation of the results, as well as the potential use of the regimen in the context of other therapy approaches that might be considered.
4. Checkpoint blockade in neoadjuvant breast cancer
In the final segment of this episode, we switch horses to early stage disease and explore the neoadjuvant setting and cancer immunotherapies. This is a topic we chose to cover in the very first ever Novel Targets episode.
Two years on, how are the data now looking?
The cancer immunotherapy space is a highly competitive one, with many companies rushing to explore their agents in numerous monotherapy and combination approaches across many tumour types.
The main advantages of evaluating therapies prior to surgeries is that they have relatively quick readouts based on surrogate markers and you know whether the approach works or not, which is not the case after surgery.
We hear from Drs Peter Schmid (Barts, London) and Leisha Emens (Johns Hopkins, now at Pittsburgh) about the endpoints and markers used, as well as the progress seen to date with two anti-PD-1/L1 antibodies, atezolizumab (AACR17 abstract #2986) and pembrolizumab (ASCO17 abstract #556) and what can be learned about immunotherapy when given to people with early stage breast cancer.”
Update: Peter Schmid presented the results of the Keynote-522 phase 3 trial of neoadjuvant cancer immunotherapy in TNBC in the Presidential Session at ESMO 2019 in Barcelona (NCT03036488). You can read an interview with him about the results on Biotech Strategy Blog (subscription required):
We also wrote some commentary for BSB subscribers about the data presented at SABCS 2019:
Podcast Sponsorship – Vignette with Dr Sandra Horning, Genentech
Genentech kindly sponsored this episode of the podcast. We’re grateful for their support! Instead of reading a corporate message, for Genentech sponsored episodes, we’re doing mini-interviews or vignettes with company scientists.
For this episode, we spoke with Dr Sandra Horning (Chief Medical Officer and Global Head of Product Development). Dr Horning is a past-president of ASCO and earlier this year published an editorial in Science on “A new cancer ecosystem.”
Update: Dr Horning retired from Genentech at the end of 2019. (Press Release).
The music in this episode is by David Schulman, from his album Quiet Life Motel.
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