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Background: In the phase 3 ARAMIS study (NCT02200614), darolutamide significantly improved metastasis-free survival in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Following the primary analysis, the study was unblinded, and placebo recipients were permitted to cross over to open-label darolutamide. Despite crossover, darolutamide significantly improved overall survival (OS). We conducted sensitivity analyses to estimate the effect of placebo-darolutamide crossover on OS., Methods: Patients with nmCRPC were randomised to oral darolutamide 600 mg twice daily (n = 955) or placebo (n = 554). Prespecified (rank-preserving structural failure time [RPSFT] and iterative parameter estimation [IPE]) and post hoc (OS-adjusted censoring and inverse probability of censoring weighting [IPCW], with weightings for baseline testosterone and prostate-specific antigen) sensitivity analyses were conducted., Results: After unblinding, 170 of 554 placebo recipients (30.7%) crossed over to darolutamide. At the final OS intention-to-treat analysis (median 11.2 months after unblinding), darolutamide significantly improved OS by 31% versus placebo (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.53-0.88; P = 0.003). The benefit increased in the analyses adjusting for crossover is as follows: RPSFT HR 0.68, 95% CI 0.51-0.90; P = 0.007; IPE HR 0.66, 95% CI 0.51-0.84; P < 0.001; OS-adjusted censoring HR 0.59, 95% CI 0.45-0.76; IPCW HR 0.63, 95% CI 0.48-0.81. The favourable safety profile of darolutamide was maintained, including in crossover patients., Conclusions: After adjusting for crossover, darolutamide reduced the risk of death by up to 41% in patients with nmCRPC. The effect of darolutamide on OS may have been underestimated in the original intention-to-treat analysis., Competing Interests: Declaration of Competing Interest All authors received support for medical writing and article processing charges from Bayer HealthCare Pharmaceuticals, Inc. N.D.S. reports consulting fees from AbbVie, Akido, Alessa Therapeutics, Amgen, Arquer, Asieris, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Clarity, Clovis, Cold Genesys, Dendreon, Eli Lilly, Exact Images, Exact Sciences, FerGene, Ferring, FIZE Medical, Foundation Medicine, GConcology, GenesisCare, Genetech, Guardant, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Photocure, Pfizer, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion and Vessi; payment for expert testimony from Ferring; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with Photocure. K.F. reports participation in advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis/AAA, Pfizer and Sanofi (honoraria paid to institution), and Arvinas, CureVac, Macrogenics and Orion (honoraria paid to self). T.L.J.T. reports grants or contracts from Astellas Pharma, Bayer and Pfizer; consulting fees from Astellas Pharma and Bayer; and participation on a data safety monitoring board or advisory board for Bayer. M.L. reports grants or contracts for research funding from Bayer, Janssen, Medivation, Myovant Sciences, Pfizer and Roche/Genentech; consulting fees from Astellas Pharma, Bayer and Janssen; payment or honoraria for speaker bureau participation from Astellas Pharma, Bayer and Janssen; and support for attending meetings and/or travel from Astellas Pharma, Bayer, Janssen, Pfizer and Zodiac. M.P.S. reports grants or contracts from Astellas Pharma, Bayer, Merck and Roche; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Bayer; payment for expert testimony from Pfizer and Roche; and support for attending meetings and/or travel from Pfizer and Roche. P.O. Jr., S.L., G.K.J., N.L. and La.A. have no other conflicts to declare. D.A.B. reports grants or contracts from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen and Merck; consulting fees from Astellas Pharma, Bayer, Janssen and Merck; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Astellas Pharma, Bayer and Janssen; and support for attending meetings and/or travel from Astellas Pharma, Bayer and Janssen. F.M.C. reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Zodiac (Adium); and support for attending meetings and/or travel from Zodiac, Bayer, Janssen and Pfizer. Lí.A. reports support for attending meetings and/or travel from Bayer. M.P. reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Myovant; and participation on a data safety monitoring board or advisory board for Pfizer. J.J.C.O. reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from AstraZeneca, Bayer and Janssen; and support for attending meetings and/or travel from Janssen. I.K. has stock or stock options in Bayer and is an employee of Bayer. C.K. is an employee of Bayer. T.S. is an employee of Orion Corporation. M.S. reports grants or contracts for research funding paid to his institution from Bayer, Eli Lilly, ESSA, Janssen Oncology and ORIC Pharmaceuticals; consulting fees from Amgen, Astellas Pharma, Bayer, Eli Lilly, Janssen Oncology, Novartis and Pfizer; and participation on a data safety monitoring board or advisory board for Amgen, Astellas Pharma, Bayer, Eli Lilly, Janssen Oncology, Novartis and Pfizer., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Palbociclib is a cyclin-dependent kinase 4/6 inhibitor that is approved in the United States for the treatment of hormone receptor‒positive (HR+)/human epidermal growth factor receptor‒2 negative (HER2-) advanced breast cancer (ABC). The objectives of this expanded access trial were to provide palbociclib in combination with letrozole to patients with HR+/HER2- ABC in Argentina, Brazil, Colombia, and Mexico who were candidates for letrozole therapy before commercial availability of palbociclib, and to evaluate the safety and tolerability of palbociclib plus letrozole., Patients and Methods: Postmenopausal women aged ≥ 18 years with HR+/HER2- ABC were eligible to participate in this study. Patients received palbociclib 125 mg once daily (3/1 schedule) and letrozole 2.5 mg once daily (continuous schedule). Safety, objective response rate (ORR), and duration of treatment were evaluated., Results: A total of 130 patients were treated with palbociclib plus letrozole (Argentina, n = 33; Brazil, n = 35; Colombia, n = 28; Mexico, n = 34). The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (70.0%), leukopenia (34.6%), anemia (33.8%), decreased neutrophil count (27.7%), and thrombocytopenia (24.6%); 22.3% of patients required a palbociclib dose reduction due to adverse events (AEs). Serious AEs were reported in 32 patients (24.6%). The ORR was 24.8% (95% confidence interval 17.6‒33.2), and the median duration of treatment was 10.6 months (range 0.1‒29.3)., Conclusion: Palbociclib in combination with letrozole was generally well tolerated with a clinically manageable safety profile; the observed ORR supported treatment benefit in Latin American women with HR+/HER2- ABC., Trial Registry: ClinicalTrials.gov, NCT02600923., (© 2023. The Author(s).)

Purpose: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type., Methods: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured., Results: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001)., Conclusions: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.

Purpose: Breast cancer (BC) in young women is uncommon and tends to present with more aggressive characteristics. To better understand and characterize this scenario in Brazil through real-world data, we performed a subanalysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973)., Methods: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2,950 women newly diagnosed with invasive BC in Brazil from January 2016 until March 2018 at 22 sites. Valid data were obtained from 2,888 patients regarding age at diagnosis and complete baseline information. To compare epidemiologic and clinicopathological features at the time of diagnosis, patients with BC were divided into two groups according to age: ≤ 40 years and > 40 years. Quantitative variables were described as means, and categorical variables were described as frequencies and percentages and compared using the Pearson's χ 2 test., Results: Of 2,888 women diagnosed with BC, 486 (17%) were ≤ 40 years old. Young women had higher educational level, most were employed and a significant number were married ( P < . 001 for all associations). Younger patients were more symptomatic at BC diagnosis ( P < . 001), and they also presented more frequently with stage III, T3/T4, grade 3 tumors, HER-2-positive, luminal B, and triple-negative subtypes., Conclusion: Brazilian women younger than age 40 years have unfavorable clinicopathological features of BC at diagnosis, with more aggressive subtypes and advanced stage when compared with older women. These differences are not explained by socioeconomic or ethnic imbalances. The causes of a higher prevalence of BC among young women in Brazil deserve additional investigation.