Italian Cohort of the Nivolumab EAP in Squamous NSCLC: Efficacy and Safety in Patients With CNS Metastases

Abstract

Background/Aim: Brain metastases are an additional challenge in patients with non-small-cell lung cancer (NSCLC) because most chemotherapy agents cannot cross the bloodbrain barrier. Nivolumab has demonstrated efficacy in patients with advanced squamous NSCLC, but because patients with central nervous system (CNS) metastases are typically excluded from registration trials, 'field-practice' data are needed. Patients and Methods: Patients in the Italian cohort of the Expanded Access Program (EAP) who had CNS metastases at baseline were analyzed. Results: Thirty-seven patients with CNS metastases received a median of six doses of nivolumab. Three patients (8%) had grade 3-4 adverse events and one patient discontinued due to an adverse event. The objective response rate was 19%. Median overall survival was 5.8 (95% confidence interval=1.9-9.8) months and median progressionfree survival was 4.9 (95% confidence interval=2.7-7.1) months. Conclusion: The safety and efficacy of nivolumab in patients with CNS metastases appear to be similar to those seen in the overall EAP cohort in Italy.Squamous non-small-cell lung cancer (NSCLC) is a distinct clinical and pathological subtype of NSCLC, characterized by a high mutation rate and substantial genomic complexity, which may contribute to its poor prognosis (1). Recently, the treatment paradigm for NSCLC has changed with the introduction of immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab and durvalumab) that block the programmed death-1 (PD-1)/programmed deathligand 1 (PD-L1) pathway and restore the antitumor immune response (2-7).Nivolumab, a fully human PD1 antibody, has been approved in the USA and the European Union for the treatment of patients with locally advanced or metastatic NSCLC whose disease progresses during or after platinumbased chemotherapy (8, 9). Median overall survival (OS) was significantly longer with nivolumab compared to docetaxel in patients who were previously treated for advanced squamous NSCLC in CheckMate 017 [9.2 vs. 6.0 months; hazard ratio for death=0.59; 95% confidence interval (CI)=0.44-0.79; p<0.001] (3), with 2-year OS rates 4265

Real world data in the era of Immune Checkpoint Inhibitors (ICIs): Increasing evidence and future applications in lung cancer

“…The vast majority of the real-world data about immunotherapy in lung cancer describes the activity, in terms of objective response rate (ORR), efficacy (in terms of overall survival, OS, and progression free survival, PFS) and the safety profile of the most common ICIs used in clinical practice (Table 1). Studies on pretreated NSCLC patients were all retrospective and showed outcomes comparable with those reported in the pivotal RCTs, with median PFS and median OS ranging from 1.8 to 4.9 months and from 7.9 to 14.6 months, respectively [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Only one study showed a remarkable outcome for patients treated with nivolumab, with a median PFS exceeding 8 months and a median OS of over 15 months; however, this may be due to the small population (n = 11) considered for analysis [23].…”

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

“…Several expanded access programs and observational studies examining patients with NSCLC treated with singleagent PD-1 or PD-L1 inhibitors found that clinical outcomes (including efficacy and safety) were similar in patients with versus without brain metastases, highlighting that both PD-1 and PD-L1 inhibitors can be effective in patients with CNS disease. [22][23][24][25] A limitation of this study is that we only allowed patients with brain metastases between 5 and 20 mm; this was chosen to avoid neurologic compromise in the event of tumor growth. Additionally, we did not evaluate patients with neurologic symptoms or those that required corticosteroid use.…”

Nivolumab for Previously Treated Patients with Non-Small-Cell Lung Cancer—Daily Practice versus Clinical Trials

“…Nivolumab therapy is routinely used in patients who have undergone primary resection or irradiation for brain metastases and whose clinical condition improved after receiving local treatment. Retrospective analyses of real-world data showed that nivolumab has intracranial activity [ 19 , 20 , 21 ]. Twenty-six percent of patients with non-squamous NSCLC in the Italian EAP had asymptomatic or controlled brain metastases [ 19 ].…”

“…In the cohort with squamous NSCLC, 10% of 372 patients had asymptomatic brain metastases. The median OS was 5.8 months (95% CI 1.9–9.8) [ 21 ]. A direct comparison of the efficacy of nivolumab in patients with and without brain metastases showed significant differences in OS [ 14 ].…”