Cell cycle regulators and benefit of adjuvant chemotherapy in patients with non-small cell lung cancer

Abstract

7100 Background: The International Adjuvant Lung Cancer Trial (IALT) demonstrated that adjuvant cisplatin-based chemotherapy improves the 5-year survival rate of patients with completely resected non-small-cell lung cancer (NSCLC) by absolute 4.1% (N Engl J Med 350, 351–360, 2004). The purpose of our study was to determine whether cell cycle regulators are of prognostic and/or predictive value in NSCLC patients who were enrolled into IALT. Methods: Expression of cell cycle regulators and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted on clinical and pathological parameters. Results: Expression of p16, p27, cyclin D1, cyclin D3, cyclin E and Ki-67 was considered as positive in 37%, 40%, 74%, 37%, 55% and 29% of tumor specimens, respectively. None of these biomarkers was significantly associated with overall survival of the patients. However, there was a relationship of borderline significance between p27 status and benefit of cisplatin-based chemotherapy (test for interaction, p = 0.04). Patients with p27-negative tumors who were treated with cisplatin-based chemotherapy had a longer overall survival than patients from the observation group (hazard ratio for death [95% CI]: 0.71 [0.55–0.93]), whereas in patients with p27-positive tumors overall survival was not different between the two groups (hazard ratio for death [95% CI]: 1.11 [0.81–1.51]). In contrast to p27, the other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy. Conclusions: NSCLC patients with p27-negative tumors appear to benefit most from adjuvant cisplatin-based chemotherapy following complete tumor resection. Thus, the predictive value of p27 should be confirmed in prospective trials. No significant financial relationships to disclose.