Nivolumab and Ipilimumab With Concurrent Stereotactic Radiosurgery for Intracranial Metastases From Non-Small Cell Lung Cancer: Analysis of the Safety Cohort for Non-Randomized, Open-Label, Phase I/II Trial

Authors

Mehmet Altan
Yan Wang
Juhee Song
James Welsh
Chad Tang
Nandita Guha-Thakurta
George R Blumenschein
Brett W Carter
Jeffrey S Wefel
Amol J Ghia
Debra N Yeboa
Mary Frances McAleer
Caroline Chung
Kristina D Woodhouse
Susan L McGovern
Chenyang Wang
Betty Y S Kim
Jeffrey S Weinberg
Tina M Briere
Yasir Y Elamin
Xiuning Le
Tina Cascone
Marcelo V Negrao
Ferdinandos Skoulidis
Renata Ferrarotto
John V Heymach
Jing Li

Publication Date

7-1-2023

Journal

Journal of Immunotherapy of Cancer

Abstract

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.

Keywords

Humans, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Ipilimumab, Lung Neoplasms, Nivolumab, Radiosurgery, Combined Modality Therapy

DOI

10.1136/jitc-2023-006871

PMID

37402581

PMCID

PMC10335483

PubMedCentral® Posted Date

7-4-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes