Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib
Autor: | Mark G. Kris, Shirish M. Gadgeel, Hira Rizvi, Helena A. Yu, Adam J. Schoenfeld, G. J. Riely, Jeffrey Girshman, A. Iqbal, Kathryn C. Arbour, Matthew D. Hellmann |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Lung Neoplasms medicine.medical_treatment Afatinib Gastroenterology B7-H1 Antigen 0302 clinical medicine Antineoplastic Agents Immunological Carcinoma Non-Small-Cell Lung PD-1 Osimertinib Aged 80 and over Aniline Compounds Hematology Middle Aged TKI ErbB Receptors Nivolumab Oncology 030220 oncology & carcinogenesis osimertinib Toxicity Female Erlotinib Adjuvant medicine.drug Adult medicine.medical_specialty EGFR Antibodies Monoclonal Humanized Disease-Free Survival 03 medical and health sciences Young Adult Internal medicine irAE medicine Humans Adverse effect Lung cancer Protein Kinase Inhibitors Thoracic tumor Aged Retrospective Studies Acrylamides business.industry Pneumonia medicine.disease Blockade 030104 developmental biology business |
Zdroj: | Annals of Oncology |
ISSN: | 1569-8041 0923-7534 |
Popis: | Background Concurrent programmed death-ligand-1 (PD-(L)1) plus osimertinib is associated with severe immune related adverse events (irAE) in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Now that PD-(L)1 inhibitors are routinely used as adjuvant and first-line treatments, sequential PD-(L)1 inhibition followed by osimertinib use may become more frequent and have unforeseen serious toxicity. Methods We identified patients with EGFR-mutant NSCLC who were treated with PD-(L)1 blockade and EGFR- tyrosine kinase inhibitors (TKIs), irrespective of drug or sequence of administration (total n=126). Patient records were reviewed to identify severe (NCI-CTCAE v5.0 grades 3–4) toxicity. Results Fifteen percent [6 of 41, 95% confidence interval (CI) 7% to 29%] of all patients treated with sequential PD-(L)1 blockade followed later by osimertinib developed a severe irAE. Severe irAEs were most common among those who began osimertinib within 3months of prior PD-(L)1 blockade (5 of 21, 24%, 95% CI 10% to 45%), as compared with >3–12months (1 of 8, 13%, 95% CI 0% to 50%), >12months (0 of 12, 0%, 95% CI 0% to 28%). By contrast, no severe irAEs were identified among patients treated with osimertinib followed by PD-(L)1 (0 of 29, 95% CI 0% to 14%) or PD-(L)1 followed by other EGFR-TKIs (afatinib or erlotinib, 0 of 27, 95% CI 0% to 15%). IrAEs occurred at a median onset of 20days after osimertinib (range 14–167days). All patients with irAEs required steroids and most required hospitalization. Conclusion PD-(L)1 blockade followed by osimertinib is associated with severe irAE and is most frequent among patients who recently received PD-(L)1 blockade. No irAEs were observed when osimertinib preceded PD-(L)1 blockade or when PD-(L)1 was followed by other EGFR-TKIs. This association appears to be specific to osimertinib, as no severe irAEs occurred with administration of other EGFR-TKIs. |
Databáze: | OpenAIRE |
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