HI Koko Crater Flowers
Over the last week or so, we’ve received a lot of questions on the following topics relating to women’s cancers in breast and ovarian carcinomas:
- APHINITY impact – pertuzumab and neratinib
- PARPs in ovarian cancer – niraparib, rucaparib and olaparib
- Seattle Genetics and Immunomedics
So this is probably a good time for a February BSB Reader Q&A post on the hot topics of the moment in cancer research.
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There was a time when it seemed that all the good news emerging in cancer research was on breast cancer, that is clearly no longer true as other tumour types have seen some leaps and bounds with different modalities, including areas previously thought to be a graveyard for big Pharma, such as metastatic melanoma, for example.
New Dawn at the Houses of Parliament
That said, after the excellent developments in hormone-sensitive disease and the identification of the HER2 oncogene, we now have CDK4/6 as a validated target in metastatic breast cancer.
Pfizer’s palbociclib (Ibrance) lead the way, with two approvals in previously untreated and relapsed ER+ HER2- advanced breast cancer. Two other companies in this field are Novartis with ribociclib and Lilly with abemaciclib. Data is being presented on all three therapies at ESMO this year.
In addition, there are some other abstracts of note that are well worth discussing.
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Updated data are often presented at conferences and therefore the results can differ from the submitted abstracts, which are sometimes submitted as placeholders based on immature data cutoffs. That was certainly the case in several examples at the ASCO GI conference in San Francisco last weekend.
After Monday’s look at new developments in the lower GI tract, we now turn our attention today to the upper GI tract with a focus on oesophageal, gastric (stomach), and gastro-esophageal junction (GEJ) cancers.
Over the last five years we have seen new approvals for targeted therapies such as HER2+ gastric cancer and relapsed refarctory gastric cancers with a VEGF inhibitor. Will that trend continue over the next five years or will we see new approaches such as immunotherapy enter the market and dominate?
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The metastatic colorectal cancer landscape is slowly changing after decades of multiple chemotherapies followed by the addition of biologics to the base chemo regimen including VEGF (bevacizumab, z-aflibercept, regorafenib) and EGFR inhibitors (cetuximab and panitimumab).
Each of these approvals have led to an incremental improvement in outcomes in different lines of therapy (LOT), but sadly with only one clinically meaningful biomarker identified (KRAS exon 2 mutant vs. wild type for EGFR inhibitors). We still don’t have a more comprehensive way to better select the likely responders from non-responders.
Progress, you might think, has been painfully slow, although the current data suggests that we have now reached a new plateau of around 30 months in overall survival. That’s going to be hard for new entrants to beat without some form of different paradigm shift.
There is only so much that can be achieved with the current strategies. You only have to look at second line VEGF inhibitors to see this incremental effect on survival:
- Bevacizumab – 1.4 months
- z-Aflibercept – 1.5 months
- Ramucirumab – 1.6 months
Overall, we can say that none of them add 2 extra months of life in that setting (never mind the cumulative cost or ‘financial toxicity’ as many attendees referred to it) and you might even consider the benefit to be fairly marginal. No biomarker has yet been identified for any of these therapies, making it impossible to select upfront those who are most likely to respond.
At the ASCO Gastrointestinal Cancers Symposium (ASCO GI) last week, we saw a repeat of the usual studies looking at new VEGF inhibitors (e.g. ramucirumab in the 2L RAISE study) and an update on the TRIBE trial (FOLFOXIRI vs FOLFIRI when either are combined with bevacizumab/Avastin).
Are there other targets that might have a meaningful impact though? If we truly want to see a more precision medicine approach evolve then we have to first find the oncogenic drivers.
With this in mind, one study in particular caught my eye and attention, but you won’t find it written up in the medical lay press and it’s not that obvious unless you know what you’re looking for.
Interested readers can sign up or sign in to learn more about this novel concept in advanced colorectal cancer below. This could be the start of a new era of research for this disease.
We hope that everyone had a relaxing holiday break and now it’s time to get back to work. Tomorrow I will review some more of my thoughts in the immuno-oncology space, since that area had a tremendous amount of progress in San Diego with lots of new ideas to process and summarise.
In the meantime, a few people have written in and asked about what was happening with overcoming resistance in various tumour types, was there anything new to say in that space that was in addition to the the detailed previews we covered before the conference?
Actually, there was a quite a few posters and presentations that caught my eye, so I thought this would be a good idea to review them here:
Lung Cancer: HER2, VEGF, T790M, EGFR, erlotinib, gefitinib, trastuzumab, bevacizumab, CO-1686, AZD9291
Prostate Cancer: mTOR, PI3K, Androgen Receptor, enzalutamide, abiraterone, CC214–2, ARN–509, BET Bromodomian inhibition, ODM–201, GDC–0980, GDC-0068, PF–04691502, BKM120, BEZ235
This morning in Amsterdam brought some interesting breast and ovarian cancer presentations that I thought deserved a quick recap – one is potentially practice changing in HER2 breast cancer and the other is a new product in development (Biomarin’s BMN 673) that is worth watching out for: