International Tailored Chemotherapy Adjuvant (ITACA) Trial, a Phase III Multicenter Randomized Trial Comparing Adjuvant Pharmacogenomic-Driven Chemotherapy versus Standard Adjuvant Chemotherapy in completely Resected Stage II-IIIA Non-Small Cell Lung Cancer
| Autor: | Paolo Pedrazzoli, Orazio Caffo, Silvia Novello, Nicolas Dickgreber, E. Stoelben, Alessandra Bearz, Michael Geissler, D. Ladage, G. Valmadre, Monika Serke, G.V. Scagliotti, Gerald Schmid-Bindert, S. Kurz, Frank Griesinger, I. Colantonio, Vanesa Gregorc, G. Borra, Valentina Monica, Gunther H. Wiest, Alessandro Follador, G. Folprecht, Alessandro Morabito, M. Schena, T. Wehler, Christian Grohé, Martin Reck, C. Kropf-Sanchen, C. Cauchi, Valter Torri, Anna Ceribelli, Luca Porcu, Christian Manegold, Antonio Santo, Rita Chiari, Luciana Irtelli, A. Meyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Oncology
medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Antineoplastic Agents thymidylate synthase Thymidylate synthase law.invention Randomized controlled trial Non-small cell lung cancer law Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Humans Lung cancer adjuvant chemotherapy excision repair cross complementation 1 messenger RNA pharmacogenomics Neoplasm Staging Chemotherapy biology business.industry Hazard ratio Hematology medicine.disease Chemotherapy Adjuvant Pharmacogenetics biology.protein ERCC1 business Adjuvant |
| Popis: | Background Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. Patients and methods Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator’s choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). Results Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. Conclusion In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm. |
| Databáze: | OpenAIRE |
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