Background: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III beta-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported. Methods: We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/mu g). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival. Results: Patients with TUBB3 protein levels >750 and <750 amol/mu g were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%;p= 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%;p= 0.09), with a statistically significant interaction between TUBB3 and treatment (p= 0.049). Conclusions: The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.

Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S. Tumori / M. Di Bartolomeo, A. Raimondi, F. Cecchi, D. Catenacci, S. Schwartz, S. Sellappan, Y. Tian, R. Miceli, A. Pellegrinelli, E. Giommoni, E. Aitini, F. Spada, G. Rosati, A. Marchet, F. Pucci, A. Zaniboni, S. Tamberi, T. Pressiani, G. Sanna, M. Cantore, S. Mosconi, P. Bolzoni, C. Pinto, L. Landi, H. Soto Parra, L. Cavanna, S. Corallo, A. Martinetti, T. Hembrough, F. Pietrantonio. - In: TUMORI. - ISSN 0300-8916. - (2020 Jun 11). [Epub ahead of print] [10.1177/0300891620930803]

Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S. Tumori.

Raimondi A;Pietrantonio F.
2020-06-11

Abstract

Background: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III beta-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported. Methods: We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/mu g). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival. Results: Patients with TUBB3 protein levels >750 and <750 amol/mu g were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%;p= 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%;p= 0.09), with a statistically significant interaction between TUBB3 and treatment (p= 0.049). Conclusions: The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.
Gastric cancer; class III beta-tubulin; taxane; adjuvant therapy;
Settore MED/06 - Oncologia Medica
11-giu-2020
TUMORI
Article (author)
File in questo prodotto:
File Dimensione Formato  
0300891620930803.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 1.02 MB
Formato Adobe PDF
1.02 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/768234
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 2
social impact