Clément Gauvain1, Enora Vauléon2, Christos Chouaid3, Emilie Le Rhun4, Laurence Jabot5, Arnaud Scherpereel6, Florent Vinas7, Alexis Benjamin Cortot8, Isabelle Monnet9. 1. GRC OncoTho, Paris-Est, UPEC, Créteil, France; Thoracic Oncology Department, CHU Lille, Univ. Lille, Siric OncoLille, Lille, France. Electronic address: clement.gauvain@wanadoo.fr. 2. Thoracic Oncology Department, CHU Lille, Univ. Lille, Siric OncoLille, Lille, France. Electronic address: enora.vauleon@gmail.com. 3. GRC OncoTho, Paris-Est, UPEC, Créteil, France. Electronic address: christos.chouaid@chicreteil.fr. 4. Service de Neuro-oncologie, Département de Neurochirurgie, CHRU de Lille, Université Lille 2, Lille, France. Electronic address: emilie.lerhun@chru-lille.fr. 5. GRC OncoTho, Paris-Est, UPEC, Créteil, France. Electronic address: laurence.jabot@chicreteil.fr. 6. Thoracic Oncology Department, CHU Lille, Univ. Lille, Siric OncoLille, Lille, France. Electronic address: arnaud.scherpereel@chru-lille.fr. 7. GRC OncoTho, Paris-Est, UPEC, Créteil, France. Electronic address: florent.vinas@chicreteil.fr. 8. Thoracic Oncology Department, CHU Lille, Univ. Lille, Siric OncoLille, Lille, France. Electronic address: alexis.cortot@chru-lille.fr. 9. GRC OncoTho, Paris-Est, UPEC, Créteil, France. Electronic address: isabelle.monnet@chicreteil.fr.
Abstract
OBJECTIVES: Although nivolumab has shown efficacy against non-small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLC patients with BMs are scarce. MATERIALS AND METHODS: We conducted a retrospective multicenter study on NSCLC patients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria. Secondary endpoints included intracerebral control rate, intracerebral and general progression-free survival (PFS), overall survival (OS) and tolerance. RESULTS AND CONCLUSION: Forty-three patients were included. BMs were locally pretreated in 34 (79%) patients and active in 16 (37%) patients. Median follow-up was 5.7 (95% CI: 2.7-8.4) months. IORR and extracerebral response rate were, respectively, 9% (95% CI: 3-23%) and 11% (95% CI: 4-26%). Intracerebral control rate was 51% (95% CI: 37-66%). Median intracerebral and general PFS lasted 3.9 (95% CI: 2.8-11.1) and 2.8 (95% CI: 1.8-4.6) months, respectively. Median OS was 7.5 (95% CI: 5.6-not reached) months. Five neurological adverse events occurred, including 1 grade-4 transient ischemic attack of uncertain imputability and 1 grade-3 neurological deficit; neither required nivolumab discontinuation. Nivolumab intracerebral activity was similar to its reported extracerebral efficacy, with an acceptable safety profile. Prospective and controlled data are needed to determine nivolumab's place in treatment of NSCLC patients with BMs.
OBJECTIVES: Although nivolumab has shown efficacy against non-small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLCpatients with BMs are scarce. MATERIALS AND METHODS: We conducted a retrospective multicenter study on NSCLCpatients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria. Secondary endpoints included intracerebral control rate, intracerebral and general progression-free survival (PFS), overall survival (OS) and tolerance. RESULTS AND CONCLUSION: Forty-three patients were included. BMs were locally pretreated in 34 (79%) patients and active in 16 (37%) patients. Median follow-up was 5.7 (95% CI: 2.7-8.4) months. IORR and extracerebral response rate were, respectively, 9% (95% CI: 3-23%) and 11% (95% CI: 4-26%). Intracerebral control rate was 51% (95% CI: 37-66%). Median intracerebral and general PFS lasted 3.9 (95% CI: 2.8-11.1) and 2.8 (95% CI: 1.8-4.6) months, respectively. Median OS was 7.5 (95% CI: 5.6-not reached) months. Five neurological adverse events occurred, including 1 grade-4 transient ischemic attack of uncertain imputability and 1 grade-3 neurological deficit; neither required nivolumab discontinuation. Nivolumab intracerebral activity was similar to its reported extracerebral efficacy, with an acceptable safety profile. Prospective and controlled data are needed to determine nivolumab's place in treatment of NSCLCpatients with BMs.
Authors: Claire M Lanier; Ryan Hughes; Tamjeed Ahmed; Michael LeCompte; Adrianna H Masters; William J Petty; Jimmy Ruiz; Pierre Triozzi; Jing Su; Stacy O'Neill; Kuonosuke Watabe; Christina K Cramer; Adrian W Laxton; Stephen B Tatter; Ge Wang; Christopher Whitlow; Michael D Chan Journal: Neurooncol Pract Date: 2019-02-05