Abstract
Purpose:The availability of immune checkpoint inhibitors has deeply changed the therapeutic scenario of patients with advanced non-small cell lung cancer (NSCLC). Up until now, chemotherapy still represents the first-line treatment for patients with advanced NSCLC not harbouring genetic mutations or lacking high expression of programmed death ligand even if the addition of immunotherapy to first-line chemotherapy has recently been shown to improve clinical outcome. We carried out a multi-institutional retrospective analysis on third-line chemotherapy with metronomic oral vinorelbine (VNR) in a series of patients with metastatic NSCLC pre-treated with first-line chemotherapy and second-line immunotherapy.Patients and methods:Thirty patients with metastatic NSCLC with progressive disease after first-line chemotherapy and subsequent immunotherapy were treated with metronomic oral VNR continuously at the fixed dose of 30 mg three times per week.Results:A partial response was achieved in 4 patients (13.3%), while 10 patients (33.3%) displayed disease stabilisation for an overall disease control rate of 46.7%. Median progression-free survival was 3.9 months (range 1–13 months) and median OS reached 8.1 months (range 4.0–24.0+ months) with a 12-month survival rate of 22%.Conclusion:Oral metronomic VNR appears to be active and safe in patients with metastatic NSCLC in progression after first-line chemotherapy and second-line immunotherapy. The results reported, although from a limited sample, may suggest its use for long-term stabilisation of the disease with good patient compliance.
Highlights
The availability of immune checkpoints inhibitors, such as nivolumab and pembrolizumab, has deeply changed the therapeutic scenario for patients with advanced non-small cell lung cancer (NSCLC) [1]
We report a multi-institutional study on third-line chemotherapy with oral metronomic VNR in a series of patients with metastatic NSCLC pretreated with firs-line chemotherapy and second-line immunotherapy
Patients included in this analysis had to fulfil the following eligibility criteria: histologically confirmed diagnosis of metastatic NSCLC according to the TNM classification version 7.0 [18]; performance status on the Eastern Cooperative Oncology Group (ECOG) scale of 0–2; measurable disease according to the RECIST criteria [19]; progressive disease after second-line therapy with immune checkpoints inhibitors; adequate renal and hepatic functions; computed tomography scan and or CNS magnetic resonance imaging available for radiological review
Summary
The availability of immune checkpoints inhibitors, such as nivolumab and pembrolizumab, has deeply changed the therapeutic scenario for patients with advanced non-small cell lung cancer (NSCLC) [1]. Oral VNR has been tested as single agent or in combination with platinum compounds in some phase I-II trials on a metronomic schedule, i.e., the administration of prolonged, non-stop low doses of otherwise active drugs [8,9,10,11]. In these studies, a flat dose in the range of 30–50 mg three times per week has been identified as the optimal schedule in terms of tolerability. Lack of major side-effects while preserving anti-neoplastic activity makes this schedule highly attractive for the management of heavily pretreated patients or elderly/frail ones [15,16,17]
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