Browsing by Author "Bines, J"

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    Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update
    (Lippincott Williams and Wilkins, 2024) Loibl, S; Jassem, J; Sonnenblick, A; Parlier, D; Winer, E; Bergh, J; Gelber, RD; Restuccia, E; Im, Y-H; Huang, C-S; Dalenc, F; Calvo, I; Procter, M; Caballero, C; Clark, E; Raimbault, A; Mcconnell, R; Monturus, E; De, Azambuja, E; Gomez, HL; Bliss, J; Viale, G; Bines, J; Piccart, M; Aebi, S; Andersson, M; Bonnefoi, H; Cameron, D; Cardoso, F; de, Haas, S; Dent, S; Fein, L; Frank, E; Gnant, M; Gomez, Moreno, H; Im, S-A; Jackisch, C; Janni, W; Krop, I; Kummel, S; Liu, T-W; Loi, S; Masuda, N; Nili, Gam-Yal, E; Nyawira, B; Pascual, T; Pienkowski, T; Rodríguez-Lescure, A; Suter, T; Thomssen, C; Tjan-Heijnen, V; Tomasello, G; Torres, Ulloa, MR; Twelves, C; Walshe, J; Wilcken, N
    Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P =.078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.
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    Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine
    (American Association for Cancer Research Inc., 2023) Asleh, K; Lluch, A; Goytain, A; Barrios, C; Wang, XQ; Torrecillas, L; Gao, D; Ruiz-Borrego, M; Leung, S; Bines, J; Guerrero-Zotano, A; Garcia-Saenz, JA; Cejalvo, JM; Herranz, J; Torres, R; de-la-Haba-Rodriguez, J; Ayala, F; Gomez, H; Rojo, F; Nielsen, TO; Martin, M
    Purpose: Predictive biomarkers for capecitabine benefit in triple-negative breast cancer (TNBC) have been recently proposed using samples from phase III clinical trials, including non-basal phenotype and biomarkers related to angiogenesis, stroma, and capecitabine activation genes. We aimed to validate these findings on the larger phase III GEICAM/CIBOMA clinical trial. Experimental Design: Tumor tissues from patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using a 164-gene NanoString custom nCounter codeset measuring mRNA expression. A prespecified statistical plan sought to verify the predictive capacity of PAM50 non-basal molecular subtype and tested the hypotheses that breast tumors with increased expression of (meta) genes for cytotoxic cells, mast cells, endothelial cells, PDL2, and 38 individual genes benefit from adjuvant capecitabine for distant recurrence-free survival (DRFS; primary endpoint) and overall survival. Results: Of the 876 women enrolled in the GEICAM/CIBOMA trial, 658 (75%) were evaluable for analysis (337 with capecitabine and 321 without). Of these cases, 553 (84%) were profiled as PAM50 basal-like whereas 105 (16%) were PAM50 non-basal. Non-basal subtype was the most significant predictor for capecitabine benefit [HRcapecitabine, 0.19; 95% confidence interval (CI), 0.07–0.54; P < 0.001] when compared with PAM50 basal-like (HRcapecitabine, 0.9; 95% CI, 0.63–1.28; P = 0.55; Pinteraction<0.001, adjusted P value = 0.01). Analysis of biological processes related to PAM50 non-basal subtype revealed its enrichment for mast cells, extracellular matrix, angiogenesis, and features of mesenchymal stem-like TNBC subtype. Conclusions: In this prespecified correlative analysis of the GEICAM/CIBOMA trial, PAM50 non-basal status identified patients with early-stage TNBC most likely to benefit from capecitabine.