Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10764

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    P1.10-021 - Phase II study of S-1 plus irinotecan for EGFR-mutated non-small cell lung cancer (NSCLC) resistant to both platinum-based chemotherapy and EGFR-TKI: NJLCG0804 (ID 1373)

    09:30 - 09:30  |  Author(s): T. Harada
    • Abstract

    Background
    From the results of recent trials, both EGFR-TKI and platinum doublet are believed to be important for patients with EGFR-mutated NSCLC. However, standard subsequent regimen after the failure of those treatments remains unclear. Some reports suggested high synergistic effect between S-1 (a novel oral fluorouracil derivative) and irinotecan against TKI-resistant cell lines. We therefore conducted this phase II trial of the combination of S-1 plus irinotecan to evaluate the efficacy and safety in EGFR-mutated NSCLC patients resistant to both platinum-based chemotherapy and EGFR-TKI.

    Methods
    Eligible patients were required advanced or recurrent NSCLC with an EGFR activating mutation, disease progression (PD) during or after second- or third-line EGFR-TKI, and previous chemotherapy including platinum doublet prior to EGFR-TKI. All patients received S-1 (80 mg/m2, day 1 to 14) orally and irinotecan (70 mg/m2, day 1 and 15) intravenously every 3 weeks. The primary endpoint was disease control rate (DCR) at 8 weeks after enrollment. The estimated accrual was 23 patients to confirm a DCR of 60% as a desirable target level and a DCR of 30 % as a lower limit of interest with alpha = 0.05 and beta = 0.10.

    Results
    From February 2009 to April 2012, 25 patients were enrolled from 6 institutions. The patients comprised 5 males and 20 females with a median age of 62 years (range, 53 to 78 years). ECOG performance status was PS 0 in 4 patients and PS1 in 21 patients. The histological subtypes were: adenocarcinoma 23 patients (92%), squamous cell carcinoma 1 patient, adenosquamous carcinoma 1 patient. EGFR activating mutations were, exon 19 deletion in 17 patients and exon 21 point mutation termed L858R in 8 patients. The current line of treatment in this study was the 3rd in 22 patients and the 4th in 3 patients. The median cycles of treatment was 4 (range 1-12). The objective responses were CR 0, PR 13, SD 8, and PD 4, giving a DCR at 8 weeks of 84.0% (95% CI, 63.9-95.5%). The overall response rate was 52.0% (95% CI, 31.3-72.2%). The median PFS was 5.0 months, whereas the median overall survival was 17.1 months. There was no significant difference in efficacy between the two types of EGFR mutations. Major grade 3 or worse toxicities included neutropenia (52%), anemia (20%), febrile neutropenia (16%), diarrhea (16%), thrombocytopenia (4%), and pulmonary thromboembolism (4%). No treatment-related death was observed.

    Conclusion
    This combination therapy with S-1 and irinotecan in EGFR-mutated NSCLC that was resistant to both platinum-based chemotherapy and EGFR-TKI showed promising efficacy with manageable toxicities. Further evaluation of this regimen in comparison with other cytotoxic agents or with irreversible EGFR-TKI is warranted.