Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001.

Abstract

INTRODUCTION:

Immune checkpoint inhibitor (ICI) therapy has been found to increase the risk/severity of immune-mediated adverse events with subsequent kinase inhibitor treatment in oncogenically driven cancers. We explored the risk for hypersensitivity with selpercatinib, a first-in-class highly selective and potent, central nervous system-active RET inhibitor, in prior ICI-treated patients with RET fusion-positive NSCLC compared with their ICI-naive counterparts.

METHODS:

Data from patients enrolled by December 16, 2019, in the ongoing phase 1/2 LIBRETTO-001 (NCT03157128) trial were analyzed for hypersensitivity reactions reported using preferred terms of hypersensitivity/drug hypersensitivity and defined as a constellation of symptoms/findings characterized by maculopapular rash, often preceded by fever with arthralgias/myalgias, followed by greater than or equal to 1 of the following signs/symptoms: thrombocytopenia, increased aspartate aminotransferase or alanine aminotransferase, hypotension, tachycardia, or increased creatinine.

RESULTS:

Of 329 patients, 22 (7%) who experienced a grade 1 to 3 hypersensitivity reaction that met the defined constellation of events were attributed to selpercatinib by investigators, and more often in prior ICI-treated (n = 17, 77%) than ICI-naive (n = 5, 23%) patients. There were 19 patients with selpercatinib-related hypersensitivity who resumed selpercatinib post-hypersensitivity with dose modification/supportive care. Furthermore, 17 patients, of whom 14 received prior ICI therapy, were still on treatment at twice daily doses of 40 mg (n = 5), 80 mg (n = 4), 120 mg (n = 4), and 160 mg (n = 4).

CONCLUSIONS:

Rates of selpercatinib-related hypersensitivity were low overall and, as with other kinase inhibitors, occurred predominantly in prior ICI-treated patients. Hypersensitivity to selpercatinib can be managed with supportive care measures regardless of prior ICI status and is reversible.

• Authors: Caroline E McCoach, Christian Rolfo, Alexander Drilon, Mario Lacouture, Benjamin Besse, Koichi Goto, Viola W Zhu, Daniel S W Tan, Stephanie Farajian, Laura A Potter, Jennifer F Kherani, Victoria Soldatenkova, Elizabeth A Olek, Catherine E Muehlenbein, Keunchil Park
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 17 Issue 6 Pg. 768-778 (06 2022) ISSN: 1556-1380 [Electronic] United States
• PMID: 35183775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immune Checkpoint Inhibitors
• Protein Kinase Inhibitors
• Pyrazoles
• Pyridines
• selpercatinib
• Proto-Oncogene Proteins c-ret

Topics

• Carcinoma, Non-Small-Cell Lung (chemically induced, drug therapy)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Humans
• Immune Checkpoint Inhibitors
• Lung Neoplasms (chemically induced, drug therapy)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-ret
• Pyrazoles
• Pyridines