Browsing by Author "Loibl, S"

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A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer
(Taylor and Francis Ltd., 2024) Turner, NC; Oliveira, M; Howell, SJ; Dalenc, F; Cortés, J; Gomez, HL; Hu, X; Jhaveri, K; Krivorotko, P; Loibl, S; Murillo, SM; Park, YH; Sohn, J-H; Toi, M; Tokunaga, E; Yousef, S; Zhukova, L; de, Bruin, E; Grinsted, L; Schiavon, G; Foxley, A; Rugo, HS
What is this summary about?: This is a summary of the article discussing the results of the CAPItello-291 study. In the study, participants had advanced breast cancer that could not be completely removed with surgery, and that was diagnosed as a type of breast cancer where tumor cells had hormone receptors (HR-positive) but did not have HER2 receptors (HER2-negative). All participants were also required to have previously received treatment with a type of therapy called an aromatase inhibitor (with or without a CDK4/6 inhibitor), but over time their cancer cells had still grown or spread. The CAPItello-291 study researchers wanted to find out if a treatment combination of the medications capivasertib plus fulvestrant worked better than placebo plus fulvestrant. Capivasertib is a drug that blocks the activity of a protein called AKT, which is found inside breast cancer cells. What are the key takeaways?: The main finding was that participants who took capivasertib plus fulvestrant lived longer without their disease getting worse (progressing) compared with those treated with placebo plus fulvestrant. This is called progression-free survival. This result was seen across all participants (median progression-free survival of 7.2 months with capivasertib plus fulvestrant vs 3.6 months with placebo plus fulvestrant). It was also seen in participants whose tumors had detectable genetic alterations in genes called PIK3CA, AKT1, and/ or PTEN (median progression-free survival of 7.3 months with capivasertib plus fulvestrant vs 3.1 months with placebo plus fulvestrant). The most common side effects experienced by participants included diarrhea and different types of rash. These were as expected (given how capivasertib works). The CAPItello-291 study is still ongoing, and more results are expected to be released in the future. What were the main conclusions reported by the researchers?: Results from the CAPItello-291 study showed that capivasertib plus fulvestrant compared with placebo plus fulvestrant improved progression-free survival in participants with HR-positive/ HER2-negative advanced breast cancer whose cancer had grown or spread despite hormone therapy (with/without a CDK4/6 inhibitor). Clinical Trial Registration:NCT04305496 (CAPItello-291) (ClinicalTrials.gov).
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.
Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer
(Massachussetts Medical Society, 2023) Turner, NC; Oliveira, M; Howell, SJ; Dalenc, F; Cortes, J; Gomez-Moreno, HL; Hu, X; Jhaveri, K; Krivorotko, P; Loibl, S; Morales-Murillo, S; Okera, M; Park, YH; Sohn, J; Toi, M; Tokunaga, E; Yousef, S; Zhukova, L; De-Bruin, EC; Grinsted, L; Schiavon, G; Foxley, A; Rugo, HS
Background AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited. Methods In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed. Results Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo. Conclusions Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. © 2023 Massachusetts Medical Society.
The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
(Nature Publishing Group, 2021) El Bairi, K; Haynes, HR; Blackley, E; Fineberg, S; Shear, J; Turner, S; de Freitas, JR; Sur, D; Amendola, LC; Gharib, M; Kallala, A; Arun, I; Azmoudeh-Ardalan F; Fujimoto, L; Sua, LF; Liu, SW; Lien, HC; Kirtani, P; Balancin, M; El Attar, H; Guleria, P; Yang WShash, E; Chen, IC; Bautista, V; Do Prado Moura, JF; Rapoport, BL; Castaneda, C; Spengler, E; Acosta-Haab, G; Frahm, I; Sanchez, J; Castillo, M; Bouchmaa, N; Md Zin, RR; Shui, R; Onyuma, T; Yang, W; Husain, Z; Willard-Gallo, K; Coosemans, A; Perez, EA; Provenzano, E; Ericsson, PG; Richardet, E; Mehrotra, R; Sarancone, S; Ehinger, A; Rimm, DL; Bartlett, JMS; Viale, G; Denkert, C; Hida, AI; Sotiriou, C; Loibl, S; Hewitt, SM; Badve, S; Symmans, WF; Kim, RS; Pruneri, G; Goel, S; Francis, PA; Inurrigarro, G; Yamaguchi, R; Garcia-Rivello, H; Horlings, H; Afqir, S; Salgado, R; Adams, S; Kok, M; Dieci, MV; Michiels, S; Demaria S; Loi, S; International Immuno-Oncology Biomarker Working Group
The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.