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Giuseppe Valmadre

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-02 - Interim Survival Analysis of Gefitinib Plus Vinorelbine in Advanced EGFR-Mutant Non-Small Cell Lung Cancer (Genoa Trial) (ID 2578)

      10:15 - 18:15  |  Author(s): Giuseppe Valmadre

      • Abstract


      Patients affected by advanced non-small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor (EGFR) are eventually destined to experience disease progression in spite of initial benefit from EGFR Tyrosine kinase inhibitors (TKIs). Preclinical studies have suggested that combining cytotoxic agents with EGFR TKIs to treat EGFR-mutant tumors may increase their inhibitory effect; in a preclinical study conducted within our Institution, the administration of vinorelbine followed by gefitinib resulted in increased activity due to synergistic effect of the combined drugs. Here we present the interim analysis of GEfitinib plus viNorelbine in Advanced EGFR mutated NSCLC (GENOA TRIAL), which was designed to investigate the role of oral vinorelbine followed by gefitinib for the management of treatment-naïve patients affected by EGFR-mutant NSCLC ( NCT02319577).


      This was a multi-centric, open-label, randomized phase II trial designed to explore activity and tolerability of vinorelbine followed by gefitinib compared to gefitinib alone in patients affected by EGFR-mutant NSCLC. The estimated enrolment was equal to 80 patients; enrolled patients were randomized (1:1) to receive oral vinorelbine (60 mg/m2) on days 1,8 followed by gefitinib (250 mg) on days 9-21 (Arm A) or gefitinib alone (250 mg) on days 1-21 (Arm B) in three-weekly cycles. The primary end-point of the study was to determine the increase in terms of 6-month progression free survival (PFS) rate with Arm A compared to Arm B, while median PFS and median overall survival (OS) were secondary end-points; PFS data were defined according to response evaluation criteria in solid tumors (RECIST) v.1.1. Safety was assessed according to common terminology criteria for adverse events (CTCAE) v. 4.0.


      Data from 44 patients (Arm A= 23; Arm B= 21) are available for this interim analysis, with a median follow up of 19.1 months. All the patients had advanced lung adenocarcinoma with EGFR mutation (exon 18=2; exon 19= 16; exon 21= 21; multiple exons= 5). The 6-month PFS rate was 48% for Arm A compared to 66% for Arm B (Fisher p= 0.24). Median PFS was 6.2 months for Arm A vs. 9.5 months for Arm B (Log Rank p= 0.17), while median overall survival (OS) was 18.2 months for Arm A and not reached for Arm B (Log Rank p= 0.12). Response rate was 47% for Arm A vs. 55% for Arm B (Fisher p= 0.76). Severe adverse events (AEs) were similarly uncommon in both arms; more specifically, two patients in Arm A experienced grade 3 white blood cells reductions, and two patients in Arm B experienced grade 3 increase of liver alanine aminotransferase. No treatment-related deaths were reported.


      At the interim analysis of GENOA Trial, the combination of oral vinorelbine plus gefitinib was not associated with increased 6-month PFS rate over gefitinib alone; similarly, no advantages in terms of response, PFS or OS were observed in the experimental arm. With regards to safety, no significant difference in terms of AEs was reported, nor unexpected toxicity was observed. The study was interrupted on the basis of this interim analysis.