TY - JOUR
T1 - Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer
T2 - analysis of the safety cohort for non-randomized, open-label, phase I/II trial
AU - Altan, Mehmet
AU - Wang, Yan
AU - Song, Juhee
AU - Welsh, James
AU - Tang, Chad
AU - Guha-Thakurta, Nandita
AU - Blumenschein, George R.
AU - Carter, Brett W.
AU - Wefel, Jeffrey S.
AU - Ghia, Amol J.
AU - Yeboa, Debra N.
AU - Mcaleer, Mary Frances
AU - Chung, Caroline
AU - Woodhouse, Kristina Demas
AU - Mcgovern, Susan L.
AU - Wang, Chenyang
AU - Kim, Betty Y.S.
AU - Weinberg, Jeffrey S.
AU - Briere, Tina M.
AU - Elamin, Yasir Y.
AU - Lee, Xiuning
AU - Cascone, Tina
AU - Negrao, Marcelo V.
AU - Skoulidis, Ferdinandos
AU - Ferrarotto, Renata
AU - Heymach, John V.
AU - Li, Jing
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/7/4
Y1 - 2023/7/4
N2 - Background Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC. Patients and methods This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS). Results Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7-24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%. Conclusion Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.
AB - Background Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC. Patients and methods This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS). Results Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7-24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%. Conclusion Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.
KW - Immune Checkpoint Inhibitors
KW - Non-Small Cell Lung Cancer
KW - Radiotherapy
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UR - http://www.scopus.com/inward/citedby.url?scp=85164245202&partnerID=8YFLogxK
U2 - 10.1136/jitc-2023-006871
DO - 10.1136/jitc-2023-006871
M3 - Article
C2 - 37402581
AN - SCOPUS:85164245202
SN - 2051-1426
VL - 11
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 7
M1 - 006871
ER -