Nivolumab (nivo) in patients (pts) with advanced (adv) NSCLC and central nervous system (CNS) metastases (mets)
Central nervous system (CNS) metastases (mets) occur in 20% to 40% of patients with advanced non–small-cell lung cancer (NSCLC) and are associated with a poor median overall survival (OS) of approximately 7 months.1,2
Goldman and colleagues evaluated the efficacy and safety of nivolumab (nivo) in this subgroup by pooling nivo-treated patients with advanced NSCLC and pretreated stable CNS mets at baseline across CheckMate-063, -017, and -057; and comparing OS with nivo versus docetaxel (doc) in patients with stable baseline CNS mets in CheckMate-017 and -057.3
A total of 46 nivo-treated patients with advanced NSCLC and pretreated baseline CNS mets from CheckMate-063 (n = 3), -017 (n = 9), and -057 (n = 34) were pooled to assess baseline characteristics, safety, and CNS progression. OS was analyzed in patients with pretreated baseline CNS mets and squamous (SQ; CheckMate-017) or non-SQ (NSQ; CheckMate-057) NSCLC treated with nivo 3 mg/kg every 2 weeks versus doc 75 mg/m2
every 3 weeks (n = 42). Of the 46 nivo-assigned patients with pretreated CNS mets, 74% had prior CNS-site radiotherapy and 85% had ≥2 extra-CNS sites of mets. Median follow-up was 8.4 months (range, 0.3-23.4); median treatment duration was 2.3 months (range, 0.03-23.3). Any grade treatment-related (TR) adverse events (AEs) occurred in 67% of patients; grade 3-4 TRAEs occurred in 7%, with no TR deaths. CNS TRAEs occurred in 5 (11%) patients and were all grade 1-2 (paresthesia, dizziness, somnolence, and tremor).
At the time of overall disease progression (PD) or last tumor assessment, 33% of patients had no evidence of CNS progression (stable/decreased CNS lesions) and 52% had unequivocal progression in the CNS. In patients with pretreated CNS mets from CheckMate-017, median OS with nivo versus doc was 4.99 months versus 3.86 months, respectively; in CheckMate-057, median OS with nivo versus doc was 7.61 months versus 7.33 months, respectively. The authors concluded that nivo was well-tolerated in patients with advanced NSCLC and preexisting CNS mets, with generally low-grade toxicities. In patients with pretreated CNS mets, nivo resulted in longer OS than doc (median OS, 8.4 months vs 6.2 months), although the risk of developing a new CNS lesion was similar in the nivo and doc treatment groups. In the CheckMate-012 arm, 17% of patients with untreated CNS mets achieved intracranial responses, including one intracranial complete remission lasting >10.5 months. These results support further investigation of nivo monotherapy in patients with NSCLC and asymptomatic CNS mets.
- Bearz A, et al. Lung Cancer. 2010;8:264-268.
- Sperduto PW, et al. J Clin Oncol. 2012;30:419-425.
- Goldman JW, et al. ASCO 2016. Abstract 9038.