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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

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

  • 12450

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    P3.06-009 - Paradoxical increase in Ki67 with neoadjuvant chemotherapy in NSCLC (ID 1143)

    09:30 - 09:30  |  Author(s): K. Fabian
    • Abstract

    Background
    Neoadjuvant chemotherapy is used to help downstage cancer, and is widely used in locally-advanced breast cancer. Studies of Ki67 proliferation index in breast cancer have been fairly extensively evaluated. Comparison of core and surgical specimens in breast cancers without exposure to chemo- or radiotherapy revealed technical variation of up to 20% in the Ki67 index score. In non-small cell lung cancer (NSCLC), however, little is known about the association of rate of change of Ki67 after neoadjuvant chemotherapy with radiographic response and clinical outcomes. We surveyed NSCLC from patients treated with neoadjuvant chemotherapy.

    Methods
    NSCLC patients treated with neoadjuvant chemotherapy were identified from 3 Hungarian hospitals and 1 community hospital in the United States. Matched pre-chemotherapy and post-surgical resection formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected and the Ki67 index was scored under an IRB exemption. We set an absolute difference of 20% between pre-chemotherapy and post-resection Ki67 scores as “meaningful” to avoid possible technical variation reported in the literature. Radiographic response to neoadjuvant chemotherapy by RECIST 1.0 criteria was also measured. Fisher’s exact test was used to measure the relationship between gender, histology, and type of chemo with “meaningful” Ki67 index. Logistic regression was used to test the relationship between Ki67 index decline rate and outcome subgroup (response/no response). Decline rate was defined as a ratio of decrease of Ki67 to its level at baseline.

    Results
    63 matched cases were identified. 46 cases were analyzable for pre-chemotherapy and post-operative Ki67, and chemotherapy regimen; 40 cases also had response criteria by RECIST. Of the 46 cases, the median patient age was 59 years (range 40-77), 23 were men, and 30 of 34 had a smoking history. There were 24 adenocarcinomas and 22 squamous cell carcinomas. Stages I, II, III, and IV were 2, 9, 31, and 4; respectively. All but two patients received a platinum-doublet, with 24 containing gemcitabine. 5 patients also received neoadjuvant radiotherapy. The mean Ki67 index scores were 35% (range 1-100%) pre-chemotherapy and 32% (0-100%) post-resection. 9 patients (19.6%) had a paradoxical “meaningful” increase in Ki67 index after neoadjuvant chemotherapy. Of the 40 patients with RECIST response data, there was 1 complete response, 34 partial responses, 4 stable diseases, and 1 disease progression. There were no statistically significant differences between gender, histology subtype, or type of platinum doublet administered associated with this paradoxical increase. There was no statistically significant difference in Ki67 decline rate between responders and nonresponders.

    Conclusion
    In this cohort of patients, there was a paradoxical “meaningful” increase in Ki67 index after neoadjuvant chemotherapy in ~20% of patients, without a clear association between histology or platinum doublet administered. For patients receiving neoadjuvant chemotherapy, the Ki67 index decline rate was not associated with radiographic response. Approximately 1/5 of NSCLC may have selection of tumor cells for a higher proliferative index when undergoing neoadjuvant platinum-based chemotherapy. The effect of this on progression-free and overall survival is being evaluated.