2026-04-13T07:07:12Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/77072025-10-31T10:49:17Zcom_2072_378070com_2072_378040col_2072_378092

Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer Matito Ariza, Judit Antunes de Melo Oliveira, Ana Mafalda Brufksy, Adam M. Waters, Simon Vivancos Prellezo, Ana Saura Manich, Cristina Wildiers, Hans Mama - Càncer - Tractament Quimioteràpia combinada Marcadors tumorals DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales Cáncer de mama metastásico; Biomarcadores; Capecitabina Càncer de mama metastàtic; Biomarcadors; Capecitabina Metastatic breast cancer; Biomarkers; Capecitabine Purpose: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS. Patients and Methods: Somatic mutations were evaluated by next-generation sequencing on primary or metastatic samples. HER2 protein expression was evaluated by central IHC, H-score, and VeraTag/HERmark. p95 expression (truncated HER2) was measured by VeraTag. HRs were estimated using unstratified Cox proportional hazards models. Results: Four hundred and twenty samples had successful sequencing: 34.0% had PIK3CA mutations and 5.5% had HER2 (ERBB2) mutations. In the combined patient populations, PIK3CA mutations trended toward shorter PFS [wild-type vs. mutant, HR = 0.81; 95% confidence interval (CI), 0.64–1.03], whereas HER2 mutations trended toward longer PFS [HR = 1.69 (95% CI, 0.97–3.29)]. Higher HER2 protein expression was associated with longer PFS [IHC 3+ vs. 2+, HR = 0.67 (0.54–0.82); H-score ≥240 versus <240, HR = 0.77 (0.63–0.93); HERmark positive vs. negative, HR = 0.76 (0.59–0.98)]. Patients whose tumors had higher HER2 protein expression (any method) derived an increased benefit from N+C compared with L+C [IHC 3+, HR = 0.64 (0.51–0.81); H-score ≥ 240, HR = 0.54 (0.41–0.72); HERmark positive, HR = 0.65 (0.50–0.84)], as did patients with high p95 [p95 ≥2.8 relative fluorescence (RF)/mm2, HR = 0.66 (0.50–0.86) vs. p95 < 2.8 RF/mm2, HR = 0.91 (0.61–1.36)]. Conclusions: PIK3CA mutations were associated with shorter PFS whereas higher HER2 expression was associated with longer PFS. Higher HER2 protein expression was also associated with a greater benefit for N+C compared with L+C. This work was supported by Puma Biotechnology Inc. (no grant number is applicable). 2022-06-17T09:46:21Z 2022-06-17T09:46:21Z 2021-11-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Clinical Cancer Research;27(21) https://doi.org/10.1158/1078-0432.CCR-21-1584 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess American Association for Cancer Research Scientia