Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small cell lung cancer: An analysis of the Spanish Lung Cancer Group pharmacogenomic study of cisplatin and docetaxel combination (PLATAX)

Abstract

7124 Background: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. Methods: We analysed data of 493 patients who received chemotherapy (cisplatin and docetaxel) within the pharmacogenomic, open-label, single-arm, multicentric PLATAX trial. Three subgroups of patients were considered: global population, patients who received at least three cycles of chemotherapy, and those who received at least six cycles. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). Relative dose intensity was analysed for both drugs. The primary endpoint was overall survival. Results: Median overall survival was 9 months (8.2–9.7). Median relative dose intensity was 0.97 for cisplatin and docetaxel. 403 patients received at least three cycles of chemotherapy, and 255 received six or more. Neutropenia appeared in 172 patients (30.8%), 72 of them G3–4 (18.6%). Dose intensity was lower in patients who presented any grade of neutropenia versus those without neutropenia in the three analyzed subgroups, for both drugs (p < 0.05). Factors associated with higher risk of death were ECOG 1–2 (HR 1.8, p = 0.00) and female (HR 1.5, p = 0.02). There were no differences in overall survival between patients with G0 vs G1–2 vs G3–4 neutropenia (8.7 vs 11.6 vs 9.6 m, p = 0.41), however the risk of death was lower in patients with ECOG 0, that presented neutropenia (HR: 0.545, IC 95%: 0.31, 0.96; p = 0.034). Conclusions: Neutropenia during chemotherapy may be associated with increased survival of patients with advanced non-small cell lung cancer and ECOG 0. Its absence is not a result of underdosing. Prospective trials are needed to assess whether neutropenia could be a biological measure of drug activity and a marker of efficacy. No significant financial relationships to disclose.