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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

Model-driven metronomic vinorelbine in heavily pre-treated metastatic NSCLC and PM patients: Results of a phase I/II study.

Metastatic Non-Small Cell Lung Cancer

Lung Cancer—Non-Small Cell Metastatic

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr e20505)

Author(s): Joseph Ciccolini, Elissa Cousin, Laure Deyme, Diane-Charlotte Imbs, Sylvanie Bonnet, Raphael Serre, Matthieu Barbolosi, Laurent Greiller, Pascale Tomasini, Melissa Galloux, Bruno Lacarelle, Dominique Barbolosi, Fabrice Barlesi; SMARTC AIX-MARSEILLE UNIV, Marseille, France; Hospital Nord Service Oncologie, Marseille, France; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; La Timone University Hospital, Marseille, France; Aix Marseille University, Marseille, France

Abstract Disclosures


Background: A phase I/II trial (NCT02555007) of oral metronomic Vinorelbine derived from a mathematical model was performed in heavily pretreated metastatic Non-Small Cell Lung Cancer or Pleural Mesothelioma patients. Progression free survival, toxicity and PK/PD endpoints were the main objectives. Methods: Metronomic scheduling was selected using a simplified phenomenological model to identify the best continuous scheduling and dosing of oral vinorelbine with a total dose of 150 mg QW. Patients were monitored on a weekly basis, efficacy was evaluated by CT scans (RECIST). Toxicity was monitored using standard CTCAE criteria. Total tumor size (TTS) was the sum of diamaters of all lesions. Computation of individual PK parameters was done with Monolix software using population approach. Results: The PK/PD model proposed the following schedule: 60 mg D1, 30 mg D2, 60 mg D4. A total of 36 patients (30 evaluable) were enrolled (22M, 13F, 24 NSCLC, 11 mesothelium, median age 69.5, range 33-85.2). Patients were all heavily pre-treated (median 3 lines, range 1-9). Grade 3+ Neutropenia was observed in 30% patients. Median PFS was 11 weeks (range: 6-16.9). Best responses included 4 PR (13%) and 18 SD (60%). Baseline total tumor size was associated with reduced PFS (HR: 1.09, p = 0.026). A large variability in drug exposure (AUC 53 %, range 26 – 501 ng.h/ml) and PK parameters (Cl 82 %, range 45-605 l/h) was observed among patients. Exposure was not associated with efficacy, apart in patients with larger TTS (i.e., > 70 mm) who seemed to have longer PFS (125 days VS. 40 days, p = 0.057). Vinorelbine exposure tended to be associated with higher risk for grade 2+ neutropenia, especially in patients with BSA < 1.8 m² (60% VS. 25.5%, p = 0.055). A non-significant trend towards baseline NLR and PFS was observed (i.e., NLR < 4: 80 days, NLR > 4: 60 days, p = 0.077). Conclusions: Metronomic vinorelbine was characterized by huge variability in drug exposure among patients. However and despite being all heavily pre-treated, 60% of stable disease and 13% of PR were achieved in these patients. Plasma exposure yielded conflicting results depending on the initial tumor burden, suggesting that patients should be carefully selected prior to be scheduled for metronomic regimen. Possible role NLR could play as a predictive marker is intriguing and should be confirmed in larger cohort.

Other Abstracts in this Sub-Category:


1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer


2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer


3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer