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Impact of early tumor shrinkage and depth of response on the outcomes of panitumumab-based maintenance in patients with RAS wild-type metastatic colorectal cancer

التفاصيل البيبلوغرافية
العنوان: Impact of early tumor shrinkage and depth of response on the outcomes of panitumumab-based maintenance in patients with RAS wild-type metastatic colorectal cancer
المؤلفون: Lorenza Rimassa, Sara Lonardi, Filippo Pagani, Federica Morano, Filippo de Braud, Giovanni Randon, Gianluca Tomasello, Giuseppina Calareso, Francesca Bergamo, Alberto Zaniboni, Michele Prisciandaro, Marta Vaiani, Salvatore Corallo, Maria Di Bartolomeo, Paolo Manca, Carlotta Antoniotti, Valeria Smiroldo, Maria Antista, Chiara Cremolini, Marco Tampellini, Matteo Clavarezza, Francesca Greco, Filippo Pietrantonio, Federica Palermo, Roberto Murialdo, Alessandra Raimondi, Patrizia Racca
المصدر: European Journal of Cancer. 144:31-40
بيانات النشر: Elsevier BV, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, Treatment duration, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Maintenance therapy, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Molecular hyper-selection, medicine, Humans, Panitumumab, In patient, Neoplasm Metastasis, RAS wild-type, Aged, Metastatic colorectal cancer, business.industry, Tumor shrinkage, Wild type, Prognosis, medicine.disease, Bevacizumab, Oxaliplatin, Survival Rate, Depth of response, Early tumor shrinkage, 030104 developmental biology, 030220 oncology & carcinogenesis, ras Proteins, Female, Fluorouracil, Colorectal Neoplasms, business, Follow-Up Studies, medicine.drug
الوصف: In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV.After blinded independent central review of ETS (≥20% reduction of the sum of target lesions) and DoR in patients enrolled in Valentino, the prognostic and predictive role of such parameters was investigated, along with their combination with PRESSING panel (uncommon genomic alterations associated with anti-EGFRs resistance beyond RAS and BRAF).One hundred and ninety-six patients were included (ETS in 132 [67.3%], median DoR: 44.1%). Both ETS and DoR ≥34% were associated with longer mPFS (p = 0.010 and p 0.001) and mOS (p = 0.006 and p 0.001). The PFS benefit of 5-FU/LV added to panitumumab maintenance, reported in the study, was independent from ETS and DoR status (interaction tests NS for both PFS and OS). However, outcomes were extremely poor in patients who received single-agent panitumumab and had no-ETS (mPFS and mOS: 7.7 and 18.7 months) or DoR 34% (mPFS and mOS: 6.5 and 18 months). Combining PRESSING panel ('molecular hyperselection') and response dynamics allowed to stratify both PFS (p 0.001 and p 0.001 for ETS and DoR, respectively) and OS (p 0.001 and p = 0.017 for ETS and DoR, respectively).ETS and DoR allow on-treatment anticipation of outcomes following an anti-EGFR-based strategy planning de-escalation, and poor radiological response may guide enrolment in crossover strategy trials. As in vivo markers of drug sensitivity, ETS and DoR may be integrated with several patient- and tumor-related factors to wisely drive decision-making on upfront treatment duration and intensity.
تدمد: 0959-8049
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::720196aa563e4533c6ed87126f610f0d
https://doi.org/10.1016/j.ejca.2020.11.017
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....720196aa563e4533c6ed87126f610f0d
قاعدة البيانات: OpenAIRE
الوصف
تدمد:09598049