Reduction in Hepatocyte Growth Factor Serum Levels is Associated with Improved Prognosis in Advanced Lung Adenocarcinoma Patients Treated with Afatinib: a Phase II Trial.

Autor: Arrieta O; Thoracic Oncology Unit, Instituto Nacional de Cancerología de México (INCan), Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico. ogar@unam.mx.; Experimental Oncology Laboratory, INCan, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, CP 14080, Mexico City, Mexico. ogar@unam.mx., Cruz-Rico G; Experimental Oncology Laboratory, INCan, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, CP 14080, Mexico City, Mexico., Soto-Perez-de-Celis E; Cancer Care in the Elderly Clinic, Department of Geriatrics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico., Ramírez-Tirado LA; Experimental Oncology Laboratory, INCan, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, CP 14080, Mexico City, Mexico., Caballe-Perez E; Thoracic Oncology Unit, Instituto Nacional de Cancerología de México (INCan), Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico., Martínez-Hernández JN; Thoracic Oncology Unit, Instituto Nacional de Cancerología de México (INCan), Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico., Martinez-Alvarez I; Thoracic Oncology Unit, Instituto Nacional de Cancerología de México (INCan), Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico., Soca-Chafre G; Experimental Oncology Laboratory, INCan, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, CP 14080, Mexico City, Mexico., Macedo-Pérez EO; Thoracic Oncology Unit, Instituto Nacional de Cancerología de México (INCan), Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico., Astudillo-de la Vega H; Laboratory of Translational Cancer Research and Cellular Therapy, Oncology Hospital, Medical Center Siglo XXI, Mexican Institute of Social Security (IMSS), CP 06720, Mexico City, Mexico.
Jazyk: angličtina
Zdroj: Targeted oncology [Target Oncol] 2016 Oct; Vol. 11 (5), pp. 619-629.
DOI: 10.1007/s11523-016-0425-x
Abstrakt: Background: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.
Methods: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437.
Results: Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients.
Conclusions: A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients.
Databáze: MEDLINE
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