Τίτλος:
AGAPP: efficacy of first-line cisplatin, 5-fluorouracil with afatinib in inoperable gastric and gastroesophageal junction carcinomas. A Hellenic Cooperative Oncology Group study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: Gastric cancer is the fifth most common neoplasm worldwide with high rates of mortality. Afatinib, a low molecular, irreversible potent inhibitor of ErbB trans-membrane receptor family, has shown promising results according to preclinical and phase I clinical trial data when combined with chemotherapy. We aimed at evaluating the safety and efficacy of the combination of cisplatin, 5FU with afatinib in molecularly unselected patients with advanced gastric cancer. Methods: Patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma received first line combination therapy of cisplatin, 5FU and afatinib every 21 days, followed by afatinib maintenance monotherapy. The primary endpoint was the Objective Response Rate (ORR); secondary endpoints included Overall Survival (OS), Progression Free Survival (PFS) and the safety profile. Unplanned exploratory analysis of HER2 and tumor mutational profile was performed. Results: Among 55 patients (ITT population) enrolled, 19 (34.5%) achieved an objective tumor response; stable disease was observed in 16 patients (29.1%) and progressive disease in 10 patients (18.2%). The ORR in the per protocol population (PP) was 42.9%. Within a median follow-up of 56 months, the median PFS and OS in the ITT population was 5.0 and 8.7 months, respectively. Seven of the 47 HER2 informative cases carried HER2 positive tumors while TP53, BRCA2 and SMAD4 were the most frequently mutated genes. The most common toxicities were neutrophil count and white blood cell decrease occurring in 56.4% of patients, followed by anemia (50.9%), hyperglycemia (40%), and diarrhea (38.2%). Conclusions: The combination of cisplatin/5FU with afatinib did not surpass the benchmarks of efficacy of the contemporary therapeutic regimens that are being applied for the treatment of patients with advanced gastric cancer. However, the observed efficacy and the improved safety profile support that our administration schedule may be further investigated to overcome toxicity problems when integrating afatinib to cytotoxic chemotherapy. Clinical trial registration: NCT01743365. © 2021 Acta Oncologica Foundation.
Συγγραφείς:
Zarkavelis, G.
Samantas, E.
Koliou, G.-A.
Papadopoulou, K.
Mauri, D.
Aravantinos, G.
Batistatou, A.
Pazarli, E.
Tryfonopoulos, D.
Tsipoura, A.
Bobos, M.
Psyrri, A.
Makatsoris, T.
Petraki, C.
Pectasides, D.
Fountzilas, G.
Pentheroudakis, G.
Περιοδικό:
Acta Oncologica
Εκδότης:
Taylor and Francis Ltd.
Λέξεις-κλειδιά:
afatinib; alkaline phosphatase; BRCA2 protein; cisplatin; creatinine; epidermal growth factor; epidermal growth factor receptor 2; fluorouracil; phosphatidylinositol 3 kinase; Ras protein; Smad4 protein; tumor suppressor p53 binding protein 1; afatinib; antineoplastic agent; cisplatin; fluorouracil, acne; adult; advanced cancer; adverse event; aged; alkaline phosphatase blood level; anemia; Article; cancer combination chemotherapy; cancer growth; cancer staging; cancer survival; cerebrovascular accident; controlled study; creatinine blood level; diagnostic error; diarrhea; disease classification; disease course; disseminated intravascular clotting; drug efficacy; drug safety; drug withdrawal; esophagus carcinoma; fatigue; female; follow up; gastrointestinal pain; gene mutation; histopathology; human; human cell; human tissue; hyperglycemia; hypoalbuminemia; hypocalcemia; hypokalemia; hyponatremia; inoperable cancer; leukocyte count; maculopapular rash; maintenance therapy; major clinical study; male; monotherapy; morning dosage; mortality; multiple cycle treatment; mutational analysis; nausea; neutrophil count; oral mucositis; overall survival; patient compliance; peripheral edema; peripheral neuropathy; phase 2 clinical trial; platelet count; progression free survival; prospective study; rash; sensory neuropathy; side effect; Stevens Johnson syndrome; stomach cancer; stomach carcinoma; stomach lymphoma; treatment interruption; treatment response time; vomiting; adenocarcinoma; gastroesophageal junction; genetics; treatment outcome, Adenocarcinoma; Afatinib; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophagogastric Junction; Fluorouracil; Humans; Treatment Outcome
DOI:
10.1080/0284186X.2021.1912822
