Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of 6 randomized trials

BMC Cancer

Francesco Perrone¹  Raimondo Di Liello¹  Maria Carmela Piccirillo¹  Clorinda Schettino¹  Piera Gargiulo¹  Laura Arenare¹  Adriano Gravina¹  Massimo Di Maio²  Fortunato Ciardiello³  Floriana Morgillo³  Carminia Maria Della Corte³  Alessia Spagnuolo⁴  Cesare Gridelli⁴  Paolo Maione⁴  Gianfranco Mancuso⁵  Vittorio Gebbia⁵  Ciro Gallo⁶  Giuliano Palumbo⁷  Alessandro Morabito⁷  Giovanna Esposito⁷ 

[1] Clinical Trials Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Via Mariano Semmola, 80131, Naples, Italy;Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Via Magellano 1, 10028, Turin, Italy;Department of Precision Medicine, Medical Oncology, Università degli Studi della Campania “Luigi Vanvitelli”, Via S. Pansini 5, 80131, Naples, Italy;Division of Medical Oncology, Ospedale “S.G. Moscati”, Contrada Amoretta, 83100, Avellino, Italy;La Maddalena Clinic for Cancer, Department Promise, Medical Oncology, Università di Palermo, 90100, Palermo, Italy;Medical Statistics, Università degli Studi della Campania “Luigi Vanvitelli”, Via L. Armanni, 80128, Napoli, Italy;Thoracic Medical Oncology, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Via Mariano Semmola, 80131, Naples, Italy;

关键词: Lung cancer;    Chemotherapy-induced neutropenia (CIN);    Retrospective-prospective design;    Prognostic factors;    Overall survival;   

DOI  :  10.1186/s12885-021-08323-4

来源: Springer

【 摘 要 】

BackgroundChemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated.MethodsWe performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias.ResultsOverall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death.ConclusionThe pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

【 授权许可】

CC BY