Potential Immunotherapy Use in Patients with mNSCLC and RET Alterations


A focused discussion on whether immunotherapy might be an effective treatment option for patients with RET-positive mNSCLC.

Joel Neal, MD, PhD: At least in my experience, immunotherapy is not particularly highly active in this case. Have you seen good responses to immunotherapy in RET-positive patients, Zosia, or Lauren?

Zosia Piotrowska, MD: I would say generally no. I think of these as similar to patients with EGFR and ALK, and I think if you look at some of the registries like the IMMUNOTARGET registry, the numbers are small but the responses are limited, so I think you have to use immunotherapy very much with caution in these patients. And like with some other oncogene-driven cancers, really often I will reserve immunotherapy only for a point when we might've exhausted both our standard of care and clinical trial targeted therapy options for these patients. I guess one other thing, Joel, to mention is just that both of these drugs have really good CNS penetration, and I think that's a really important point. And again, it's just so nice when we have these drugs that have good CNS activity in the clinic and I think both pralsetinib and selpercatinib have demonstrated CNS activity, and for patients who present with brain mets are a good choice.

Joel Neal, MD, PhD: Lauren, any thoughts on immunotherapy in this patient population?

Lauren Welch, MSN, NP-C, AOCNP: Yeah, I guess defining what we mean by immunotherapy, I think what we're talking about today is checkpoint inhibitors. And I agree exactly with what Zosia said: We're predominantly saving that for when we've tried everything else that's been exhausted. But we have had some anecdotal successes with some novel IO mechanisms in these kinds of patients, so we're not afraid to, if they've exhausted all of their targeted therapies and chemo, to try some of these new novel IO agents. And sometimes those newer mechanisms are able to work better than standard checkpoint inhibitors.

Joel Neal, MD, PhD: Yes, platinum-based therapy is of course the option, standard option after use of the RET inhibitors. While the platinum and pemetrexed is compelling, I think the addition of anti-angiogenics or even immunotherapy, for lack of anything else, is perfectly reasonable. But not a lot of responses to immunotherapy itself.

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