ASCO 2017 — Some Take-Aways
Several members of the Bionest team attended ASCO this year — the biggest cancer conference in the world, attracting over 30,000 oncology researchers, biopharmaceutical executives, public health experts, investors and journalists.
As we predicted in our pre-ASCO post, one of the biggest take-aways from the conference was the continued and ever-growing emphasis on combination trials. Not only was there anticipated data from trials of immuno-oncology (IO) combinations, but trials of IO therapies with a variety of targeted anticancer drugs. According to a report by EP Vantage, there are now more than 765 such studies underway, usually featuring at least one checkpoint inhibitor along with a different type of treatment. That’s a tripling of the number of reported studies only 18 months ago. While we are starting to see clinical data from these trials, it is still difficult to predict what will work. Perhaps the mostly closely watched are the combination trials with IDO-1 inhibitors or PARP inhibitors.
While there is a lot of hopefulness that some of these cancer combinations will bring real treatment advances, to date there have been no home-runs. One of the most highly anticipated trials — that of Keytruda and Incyte’s IDO-1 inhibitor epacadostat showed a 35% overall response rate. However, with the safety profiles of various combinations a concern, the consistent safety profile for this combination compared to Keytruda alone was encouraging. Also of concern in the combination field, as we have observed before, is what happens to treatment costs when two or more expensive new therapies are combined — another hot topic of discussion this year.
Tumor agnostic approaches to cancer treatment also received considerable attention at ASCO this year. Following on the approval of Merck’s Keytruda for the treatment of cancers with a particular genetic marker, Loxo presented data showing a 76% overall response rate to larotrectinib in patients with 17 different unique cancer types who exhibited a TRK fusion mutation. The company plans to seek approval for its drug based on this genetic marker by early 2018.
So what makes a good target for a tumor agnostic approach to approval? And how do you know when you have one? Merck was able to identify its MSI-H/dMMR target from an examination of tumor biopsies that turned up a high prevalence of the mutations in colorectal cancers and then a somewhat lower occurrence in a variety of other cancers, which supported the drug’s recent tumor-agnostic approval. Loxo’s marker is related to a variety of rare orphan cancer indications. But unless there is already clinical data to back up the importance of a particular marker, how many tumor types do you need to evaluate to support a tumor agnostic strategy? And if the mutation appears not only in rare cancers but in a cancer affecting a much larger patient population, will FDA require a separate trial in that larger population to support approval?
Amongst all the positive data, ASCO presentations also held some disappointments. We were eagerly watching for the results of Roche/Genentech’s Phase 3 APHINITY trial in Her-2 positive early breast cancer, combining Perjeta (pertuzumab) with Herceptin (trastuzumab) and chemotherapy. Unfortunately, while the combo did out-perform Herceptin alone, the benefit was only slight — 94.1% survival in the combo arm versus 93.2% for Herceptin alone.
Finally, our predictions over the years about the rising importance of diagnostics in general continues to come true. We noted a big increase in the prevalence of diagnostic companies with prominent booths on the exhibition hall floor this year, including Foundation Medicine and key liquid biopsy player, Guardant Health. Current and future utility of liquid biopsy assays were at the forefront of conversation at ASCO. Not surprisingly, the case presented for moving beyond a singular companion diagnostic (PD-L1) for immunotherapy selection was strong. Ongoing work to profile the tumor microenvironment with respect to inflammatory signatures is predicted to become important (i) to address PD-(L)1 nonresponders and (ii) in future scenarios of IO combinations. Be sure to watch for upcoming blog posts in which we discuss the exciting progress for liquid biopsy utility and key trends for more comprehensive IO diagnostics.