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ASCO 2026 | Comparing selpercatinib and pralsetinib in RET-positive NSCLC
Sanjay Popat, MBBS, FRCP, PhD, Royal Marsden Hospital, London, UK, discusses the two licensed RET inhibitors in non-small cell lung cancer (NSCLC), selpercatinib and pralsetinib, which have shown superiority to standard chemotherapy in randomized Phase III studies. Both have distinct toxicity profiles, with selpercatinib associated with higher rates of ALT and QTc prolongation, and pralsetinib linked to an increased infection risk. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
So we now have, at least in the US, two licensed approved RET inhibitors, selpercatinib and pralsetinib. Both are RET selective inhibitors. Both have their pros and both have particular issues associated with them. And both have been demonstrated in randomized phase three studies to be superior to standard of care chemotherapy with or without immunotherapy. It’s difficult to directly compare head to head these two because they’ve not been formally evaluated...
So we now have, at least in the US, two licensed approved RET inhibitors, selpercatinib and pralsetinib. Both are RET selective inhibitors. Both have their pros and both have particular issues associated with them. And both have been demonstrated in randomized phase three studies to be superior to standard of care chemotherapy with or without immunotherapy. It’s difficult to directly compare head to head these two because they’ve not been formally evaluated. And the patient population is slightly different. But the hazard ratios are very, very similar. And as the discussant Dr. Chin said at ASCO, both of these drugs represent good options as endorsed by guidelines in the first-line setting. Both, however, have slightly different toxicity profiles. We do see slightly higher rates of ALT and QTc prolongation with selpercatinib than we are seeing with pralsetinib. And with pralsetinib, we see an infection risk that we’re not seeing with selpercatinib. So both represent options. Both have slightly different toxicity profiles that one may wish to consider in the treatment decision-making process.
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