TY - JOUR
T1 - Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases
AU - Zhang, Michael
AU - Rodrigues, Adrian J.
AU - Pollom, Erqi L.
AU - Gibbs, Iris C.
AU - Soltys, Scott G.
AU - Hancock, Steven L.
AU - Neal, Joel W.
AU - Padda, Sukhmani Kaur
AU - Ramchandran, Kavitha J
AU - Wakelee, Heather
AU - Chang, Steven D.
AU - Lim, Michael
AU - Hayden Gephart, Melanie
AU - Li, Gordon
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
PY - 2021/3
Y1 - 2021/3
N2 - Introduction: Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described. Methods: We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan–Meier and Cox proportional hazard analyses were performed. Results: A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0–49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF. Conclusions: In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.
AB - Introduction: Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described. Methods: We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan–Meier and Cox proportional hazard analyses were performed. Results: A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0–49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF. Conclusions: In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.
KW - Brain metastasis
KW - Immune-related adverse events
KW - Immunotherapy
KW - Non-small cell lung cancer
KW - Pembrolizumab
KW - Progression
UR - http://www.scopus.com/inward/record.url?scp=85098877828&partnerID=8YFLogxK
U2 - 10.1007/s11060-020-03686-3
DO - 10.1007/s11060-020-03686-3
M3 - Article
C2 - 33415659
SN - 0167-594X
VL - 152
SP - 125
EP - 134
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -