Author of

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12665

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    P3.11-017 - Observational post-authorization prospective study to characterize the incidence of EGFR positive mutation (M+) in advanced or metastatic non-small cell lung cancer (aNSCLC) patients (P) and their clinical management in Galicia (NCT01717105): A Galician Lung Cancer Group study (GGCP 048-10) (ID 1695)

    09:30 - 09:30  |  Author(s): L. Santomé
    • Abstract

    Background
    The presence of mutations in the gene encoding the Epidermal Growth Factor Receptor (EGFR) predicts that P with aNSCLC may respond better to Tyrosine Kinase Inhibitors (TKIs). Recently, the Spanish REASON study has reported that the rate of EGFR mutations is 11.6% in Spain; however the mutation rate and the clinical management of aNSCLC carrying EGFR mutations in Galicia are still unknown.

    Methods
    All newly diagnosed aNSCLC P in 9 Galician centers were prospectively included for a 13-month period. P with M+ disease were followed for at least 9 months (m) in order to characterize their clinical management. Mutation testing was performed on available tumor and plasma samples, through a central laboratory using the EGFR RGQ PCR Kit™ (Qiagen). Pre-planned exploratory objectives included comparison of EGFR mutation status between matched baseline tumor and plasma samples.

    Results
    From February 2011 to March 2012, 198P were included in the study. Median age was 65.5 years (range 34-85). 76.3%P were men, 21.7% were never-smokers, 45.5% ex-smokers, and 32.8% current smokers. PS 0-1: 67.1%. 78.3% had non-squamous histology (68.7% adenocarcinoma, 8.1% large-cell carcinoma, 1% adenosquamous carcinoma, and 0.5% non-specified) and 21.7% p had squamous-cell carcinoma. Sample type provided included: 57.6% tissue, 42.4% cytology. Median turnaround time (TAT) was 8 days. Mutation rate in evaluable samples: 13.6% in tumor, tissue or cytology (25P) (11P had exon 19 deletion, 8P L858R mutation, 2P exon 20 insertions and 1P L861Q mutation); 5.9% in plasma. Tumor and plasma EGFR mutation status concordance rate was 90.8%.Plasma test sensitivity was 40%. Mutation rate did not vary by sample type (13.9% tissue, 13.2% cytology). A higher mutation rate was found in never smokers (42.5%), females (38.6%) and adenocarcinoma (19.8%). 23 out of 25 M+ P received first line treatment and 2P only best supportive care. 21P were treated with TKI (Gefitinib), 1P with chemotherapy (CT) (Cisplatin/docetaxel/bevacizumab) and 1P with CT+TKI (Carboplatin+Gefitinib). 20P were evaluated for response. 3P were lost for follow up. At data cut off (31/12/2012), with a median follow up of 9.8m, 14P had partial response (70%), 2 stable disease (10%) and 4P progressive disease (20%). Median progression free survival was 9.7m. 8 out of 20P (40%) received 2[nd] line treatment (7 CT and 1 TKI). 12 out of 25P had died, 3P were lost for follow up and 10P were still alive.

    Conclusion
    Mutation analysis is feasible in clinical practice for aNSCLC patients in Galicia and allows the customization of treatment based on molecular criteria. Despite of the relatively small number of patients in this study, EGFR testing in plasma has a low sensitivity and therefore should not substitute tissue testing although it could be an alternative for those patients without tissue samples.

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    P3.11-019 - Gefitinib efficacy in EGFR mutated Non Small Cell Lung Cancer (NSCLC) patients based on type of mutation: a study from the Galician Lung Cancer Group. (ID 1710)

    09:30 - 09:30  |  Author(s): L. Santomé
    • Abstract

    Background
    Screening for Epidermal Growth Factor Receptor (EGFR) mutation is a key molecular test for management of lung cancer. Patients who respond well to an EGFR inhibitor harbor certain mutations in the EGFR exons 18, 19 or 21. An additional mutation in EGFR exon 20 is known to be responsible for acquired resistance to this therapy.

    Methods
    We conducted an analysis of Galician advanced lung cancer patients who were tested positive for EGFR kinase domain mutations determination and were treated with gefitinib. Frequency and type of EGFR mutations and the clinical response in our area were explored. The aim is to analyse the pattern of response, toxicity, progression free survival and overall survival based on the type of EGFR mutation.

    Results
    Forty-six patients with EGFR mutations were collected, 36 women and 10 men. The median age was 67 years (43-86). Majority of the patients in the study had PS 0-1 (93%) and adenocarcinoma (96%) in the pathological study. The most frequent sites of metastasis were lymph nodes (59%), bones (33%), lung (33%) and pleura (33%). The median duration of treatment was 6 months. Progression disease was the most frequent reason of discontinuation of gefitinib; in 9 patients was discontinued because of toxicity. Ten patients were switched to cytotoxic chemotherapy and 10 patients continued with erlotinib. Twenty patients were detected to be positive for mutation in exon 19, 4 patients in exon 20 and 20 patients in exon 21. The L858R point mutation in exon 21 was observed in 14 patients and the L833F point mutation in the same exon was observed in 1 patient. Thirty-five patients were included in the response analysis. The response ratio to gefitinib was 57%. Depending on the type of mutation, the response in exon 19 mutation patients was 64%, in exon 20 patients was 0% and in exon 21 patients was 60%. Rash or acne was the most frequent toxicity (48%), only 2% was grade 3-4. Diarrhea and dysnea were the main toxicities grade 3-4 (9% both), without statistical differences based on type of mutation (p=0.78) . Progression free survival (PFS) of patients with EGFR mutations was 6 months. Patients with mutation in exon 19 had 9 months compared to 6.4 months for patients with exon 21 mutation, presenting a statistically significance difference (p=0.002). Overall survival (OS) was 17 months for EGFR mutations patients (19 months for exon 19 mutation patients and 14 months for exon 21 mutation patients; p=0.119)

    Conclusion
    Pacients in our area with exon 19 EGFR kinase domain mutations treated with gefitinib have higher PFS compare to exon 21 EGFR kinase domain mutations. Exon 20 mutation in our patients is responsible for resistance to gefitinib.