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

  • 10755

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    P1.10-012 - Activity of S-1 for non-small cell lung cancer pretreated with or without pemetrexed. (ID 882)

    09:30 - 09:30  |  Author(s): S. Mikura
    • Abstract

    Background
    S-1, a 5-fluorouracil derivative, and pemetrexed (PEM) are antimetabolites that both mainly target thymidylate synthase. S-1 received approval as a therapeutic drug for treating non-small cell lung cancer (NSCLC) in Japan in December 2004, and has been primarily used as a single agent for salvage chemotherapy. To our knowledge, there has been no clinical evidence whether the activity of S-1 is influenced by PEM resistance.

    Methods
    Patients with pretreated NSCLC who underwent S-1 monotherapy were identified from an institutional database. This study was approved by the institutional review board. Eligible patients were classified into three groups; patients with non-squamous NSCLC pretreated with PEM (PEM+) or not (PEM−), or those with squamous cell lung cancer (SQ). Progression-free survival (PFS) and overall survival (OS) from S-1 administration were estimated using the Kaplan-Meier method and the log-rank test was used for inter-group comparisons. Impacts of prior PEM therapy on PFS and OS were examined using Cox proportional hazards modeling with variables including number of prior chemotherapy regimens, histological subtype of NSCLC, sex and age (<70 vs. ≥70 years).

    Results
    We identified 125 patients who underwent S-1 monotherapy for pretreated NSCLC. Median age was 69 years (range, 39-86 years), with 31% female. Histological subtype was 82 (66%) adenocarcinoma, 33 (26%) squamous cell carcinoma and 10 (8%) NSCLC not otherwise specified. Number of prior chemotherapy regimens was one in 32 (26%), two in 54 (43%), three in 26 (21%) and four or more in 13 (10%) patients. Among 108 patients with measurable disease, response rate was 12% and disease control rate was 45%. Response rates for S-1 monotherapy as second-, third- and fourth-line chemotherapy were 19% (5/27), 13% (6/45) and 9% (2/23), respectively. Forty-eight patients had received PEM-based chemotherapy prior to S-1 administration. Median PFS were 2.0 months for the PEM− group (reference), 2.1 months for the PEM+ group (crude hazard ratio (HR) 1.11, 95%CI 0.73-1.69, p = 0.6), and 2.2 months for SQ group (crude HR 0.72, 95%CI 0.44-1.15, p = 0.2). Median OS were 4.5 months for the PEM− group (reference), 5.9 months for the PEM+ group (crude HR 0.65, 95%CI 0.41-1.03, p = 0.07), and 8.4 months for SQ group (crude HR 0.76, 95%CI 0.47-1.23, p = 0.3). Multivariate analyses revealed that only female sex was associated with longer PFS (HR 0.59, 95%CI 0.38-0.91, p = 0.02) and OS (HR 0.58, 95%CI 0.36-0.91, p = 0.01), with history of PEM therapy or histological subtype exerting no influence.

    Conclusion
    Activity of S-1 is unaffected by prior PEM therapy. These results are compatible with recent preclinical findings. Further study is warranted.