Cancer research communications · 2026
Evaluation of Biomarkers for Sacituzumab Govitecan in Metastatic Non-Small Cell Lung Cancer: Insights From the EVOKE-01 Study.
СтатьяКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
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Felip Enriqueta, Kuo Peiwen, Garrido Pilar, Chouaid Christos, Mountzios Giannis, Tiseo Marcello, Daniel Davey B, Zavodovskaya Marianna, Tang Shan, Su-Feher Linda, Patel Riddhi, Park Joseph K, Jürgensmeier Juliane M, Summers Yvonne
Аннотация
PURPOSE: This exploratory analysis assessed predictive biomarkers for sacituzumab govitecan (SG) in the open-label, phase III EVOKE-01 study of SG versus docetaxel in non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS: Trophoblast cell-surface antigen (Trop) 2 membrane protein expression was analyzed using immunohistochemistry in the Trop-2 biomarker-evaluable population (BEP). Circulating tumor DNA (ctDNA) analyses evaluated baseline and reduction of ctDNA with treatment and identified oncogenic driver alterations (KRAS, TP53, KEAP1, and STK11) and other relevant mutations in the ctDNA BEP.
RESULTS: The median overall survival (OS) with SG versus docetaxel was 8.9 versus 9.8 months [hazard ratio (HR) = 0.96; 95% CI, 0.68-1.38] and 11.8 versus 10.7 months (HR = 0.89; 95% CI, 0.60-1.32) in subgroups with Trop-2 histologic scores greater than or equal to the median and less than the median, respectively. As expected, the median OS was longest in patients with undetectable baseline ctDNA. Reduction in ctDNA was observed after the first cycle with either treatment. KRAS driver alterations and potential immunotherapy resistance mutations (TP53, KEAP1, and STK11) were negative prognostic factors. Patients with TP53 mutations derived more benefit from SG than docetaxel. SG activity was observed independent of DNA damage repair (DDR) mutations.
CONCLUSIONS: Trop-2 expression did not identify patients benefiting more from SG than from docetaxel. ctDNA reduction supported SG as active therapy in NSCLC. Evaluation of clinically relevant biomarkers in NSCLC identified KRAS, TP53, STK11, and KEAP1 mutations as negative prognostic factors in these second line-treated patients.
SIGNIFICANCE: The biomarker analyses of the phase III EVOKE-01 trial found that neither Trop-2 expression nor DDR alterations predicted benefit with SG versus docetaxel. Reduction in ctDNA in both treatment arms confirmed the activity of SG in this population. Further evaluation of predictive biomarkers for SG response in NSCLC is warranted.
PATIENTS AND METHODS: Trophoblast cell-surface antigen (Trop) 2 membrane protein expression was analyzed using immunohistochemistry in the Trop-2 biomarker-evaluable population (BEP). Circulating tumor DNA (ctDNA) analyses evaluated baseline and reduction of ctDNA with treatment and identified oncogenic driver alterations (KRAS, TP53, KEAP1, and STK11) and other relevant mutations in the ctDNA BEP.
RESULTS: The median overall survival (OS) with SG versus docetaxel was 8.9 versus 9.8 months [hazard ratio (HR) = 0.96; 95% CI, 0.68-1.38] and 11.8 versus 10.7 months (HR = 0.89; 95% CI, 0.60-1.32) in subgroups with Trop-2 histologic scores greater than or equal to the median and less than the median, respectively. As expected, the median OS was longest in patients with undetectable baseline ctDNA. Reduction in ctDNA was observed after the first cycle with either treatment. KRAS driver alterations and potential immunotherapy resistance mutations (TP53, KEAP1, and STK11) were negative prognostic factors. Patients with TP53 mutations derived more benefit from SG than docetaxel. SG activity was observed independent of DNA damage repair (DDR) mutations.
CONCLUSIONS: Trop-2 expression did not identify patients benefiting more from SG than from docetaxel. ctDNA reduction supported SG as active therapy in NSCLC. Evaluation of clinically relevant biomarkers in NSCLC identified KRAS, TP53, STK11, and KEAP1 mutations as negative prognostic factors in these second line-treated patients.
SIGNIFICANCE: The biomarker analyses of the phase III EVOKE-01 trial found that neither Trop-2 expression nor DDR alterations predicted benefit with SG versus docetaxel. Reduction in ctDNA in both treatment arms confirmed the activity of SG in this population. Further evaluation of predictive biomarkers for SG response in NSCLC is warranted.
Предметные рубрики MeSH
HumansCarcinoma, Non-Small-Cell LungLung NeoplasmsBiomarkers, TumorFemaleAntigens, NeoplasmCamptothecinCell Adhesion MoleculesMaleDocetaxelMiddle AgedMutationAgedKelch-Like ECH-Associated Protein 1Tumor Suppressor Protein p53Proto-Oncogene Proteins p21(ras)AMP-Activated Protein Kinase KinasesAdultPrognosisImmunoconjugatesAntibodies, Monoclonal, Humanized