Advanced GIST: The Impact of Newly Approved Agents

Andrew Wagner, MD: Sharesh, could you discuss how the availability of these newer options will impact the care of your patients with advanced GIST [gastrointestinal stromal tumors]? In particular, how Intrigue and INVICTUS will be helpful in the context of current options, unmet needs. And whom would you consider the use of ripretinib in, and at what point in therapy?

Shreyaskumar, Patel, MD: At the outset, it’s important to just say that we are all excited about having yet another effective agent that’s relatively manageable in terms of toxicity profile and improves patient quality-of-life parameters. That would be ripretinib for the fourth-line setting, KIT-mutant GIST [gastrointestinal stromal tumors] population, right. The label indicates that that would be the population that we would use it in. We’ve already discussed the fact that there would be good merit for the drug’s use in earlier-line settings.

The data from the INTRIGUE trial will clearly help us define that a little better. In general, as everyone on the call realizes as long as we have an approved agent for a given disease, the exact line of therapy in terms of standard-of-care practice may not necessarily be strictly adhered to. To what extent ripretinib will start getting used in earlier-line settings is an open question that remains to be seen. The Intrigue trial results will definitely impact whether that happens.

From the avapritinib standpoint, it’s commercially available for the D842V-mutant population, where it is the standard-of-care treatment. Would that drug would be used off-label in KIT-mutant GIST? That is certainly a possibility. It would be nice if we could fine-tune the biomarker where it has the most activity. As you alluded to earlier, it’s going to take a little more work to try to answer those questions.

In the meantime, having 2 new agents in the therapeutic armamentarium that allows us to treat these patients is very helpful. Over the years, what has happened to the natural history of this disease is that the drop-off rates from first line to second line to third line to beyond lines is slowly drifting away. That is, as you mentioned earlier, Andy, we’re getting better at proactive management of toxicities of the drug. We’re getting better at proactive management of tumor-related symptoms. Thus, allowing us to continue some form of the kinase inhibition in this patient population so they can live longer.

Andrew Wagner, MD: This has been extremely informative. Thank you, Dr Patel, for this insightful discussion. And thank you to our audience for watching this Targeted Oncology™ presentation on precision medicine. We hope you found this discussion to be useful and informative.

Transcript edited for clarity.

Andrew Wagner, MD, reports the following disclosures: Consulting with Deciphera, Daiichi-Sankyo, NanoCarrier. He also reports research funding to his institution with Daiichi-Sankyo, Eli Lilly, Karyopharm, Plexxikon, Aadi Biosciences.