Cell cycle regulators and outcome of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer:: The international adjuvant lung cancer trial biologic program

Purpose The International Adjuvant Lung Cancer Trial (IALT) demonstrated that adjuvant cisplatin-based chemotherapy improves the survival of patients with completely resected non-small-cell lung cancer (NSCLC). The purpose of our study was to determine whether cell cycle regulators are of prognostic and/or predictive value in patients who were enrolled onto the IALT. Patients and Methods Expression of p27(Kip1), p16(INK4A), cyclin D1, cyclin D3, cyclin E, and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic parameters. Results There was a relationship between p27(Kip1) status and benefit of cisplatin-based chemotherapy (test for interaction, P = .02). Among patients with p27(Kip1)-negative tumors, cisplatin-based chemotherapy resulted in longer overall survival compared with controls (adjusted hazard ratio [HR] for death = 0.66; 95% CI, 0.50 to 0.88; P = .006). In patients with p27(Kip1)-positive tumors, overall survival was not different between patients treated with cisplatin-based chemotherapy and controls (adjusted HR for death = 1.09; 95% CI, 0.82 to 1.45; P = .54). The other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy. None of these biomarkers was significantly associated with overall survival of the patients in the total study population. Conclusion NSCLC patients with p27(Kip1)-negative tumors benefit from adjuvant cisplatin-based chemotherapy after complete tumor resection. Before establishing p27(Kip1) as a routine marker for selection of patients for adjuvant chemotherapy, the predictive value of p27(Kip1) has to be confirmed in patients from other trials.