Severe immune related adverse events are common with sequential PD-(L)1 blockade and osimertinib
Menée à partir de données portant sur 126 patients atteints d'un cancer du poumon non à petites cellules présentant une mutation EGFR, cette étude analyse la survenue d'événements indésirables de nature immunitaire en lien avec les anti-PD-(L)1 et les inhibiteurs de tyrosine kinase de l'EGFR dispensés de façon séquentielle
Background : Concurrent PD-(L)1 plus osimertinib is associated with severe immune related adverse events (irAE) in EGFR mutant 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-TKIs, irrespective of drug or sequence of administration (total n = 126). Patient records were reviewed to identify severe (grade 3-4) toxicity. Results : Fifteen percent (6 of 41, 95% CI 7-29%) 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 3 months of prior PD-(L)1 blockade (5 of 21, 24%, 95% CI 10-45%), as compared with > 3-12 months (1 of 8, 13%, 95% CI 0-50%), > 12 months (0 of 12, 0%, 95% CI 0-28%). By contrast, no severe irAEs were identified among patients treated with osimertinib followed by PD-(L)1 (0 of 29, 95% CI 0-14%) or PD-(L)1 followed by other EGFR-TKIs (afatinib or erlotinib, 0 of 27, 95% CI 0-15%). IrAEs occurred at a median onset of 20 days after osimertinib (range 14-167 days). 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.
Annals of Oncology 2019