OBJECTIVE:In the phase 3, multi-national, open-label, randomized innovaTV 301/ENGOT-cx12/GOG-3057 trial (NCT04697628), tisotumab vedotin as second- or third-line therapy significantly improved survival versus chemotherapy in patients with recurrent or metastatic cervical cancer. We report a post hoc analysis of patient-reported outcomes on health-related quality of life from innovaTV 301. METHODS:Patients were randomized 1:1 to tisotumab vedotin or investigator's choice of chemotherapy. Pre-specified secondary end points included assessment of health-related quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cervical Cancer Module, and EuroQol 5-Dimension 5-Level. This post hoc analysis assessed change from baseline to cycle 13 using a mixed model for repeated measures and time to clinically meaningful deterioration (≥10-point change) or disease progression/death using a Cox proportional hazards model in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module subscales, both adjusted for baseline factors. Proportion of patients with ≥10-point change from baseline in subscales were compared between arms. RESULTS:Mean compliance rates across patient-reported outcome instruments were high (>82%) from baseline to cycle 13. Mixed model for repeated measures analyses showed that patient-reported health-related quality of life, functioning, and symptoms were maintained with tisotumab vedotin therapy over the course of treatment, with no differences by arm. The proportion of patients reporting clinically meaningful (≥10-point) improvement was greater with tisotumab vedotin versus chemotherapy for most European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module subscales. In patients who showed deterioration, time to clinically meaningful deterioration was slower with tisotumab vedotin versus chemotherapy for most European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module subscales, most notably nausea/vomiting, pain, dyspnea, insomnia, symptom experience, and lymphedema. CONCLUSIONS:Results suggest tisotumab vedotin maintained health-related quality of life in patients with previously treated recurrent or metastatic cervical cancer and, together with clinical outcomes with innovaTV 301, support tisotumab vedotin as a treatment option in this setting. TRIAL REGISTRATION NUMBER:NCT04697628.

Pembrolizumab plus chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in the phase 3 randomized KEYNOTE-355 study in participants with previously untreated, advanced triple-negative breast cancer (TNBC) with PD-L1 combined positive score (CPS) ≥ 10. Among participants with clinical benefit from pembrolizumab plus chemotherapy, discontinuation of chemotherapy before pembrolizumab for any reason was associated with similar median PFS and OS to that in the overall population. Additionally, we further characterized immune-mediated adverse events (AEs) in KEYNOTE-355. Most immune-mediated AEs were manageable with treatment interruption and supportive care. In participants treated with pembrolizumab plus chemotherapy with immune-mediated AEs, there appeared to be numerical improvement in efficacy. This analysis provides additional information on the use of pembrolizumab plus chemotherapy as standard-of-care therapy in patients with previously untreated, advanced TNBC with PD-L1 CPS ≥ 10. This trial is registered at ClinicalTrials.gov (NCT02819518; registration date, June 28, 2016).

PURPOSE:Patients with platinum-resistant/platinum-refractory high-grade serous ovarian cancer (HGSOC) without a BRCA mutation have poor prognosis and limited treatment options. We report efficacy and biomarker data from EPIK-O, which investigated alpelisib + olaparib versus single-agent chemotherapy in these patients. PATIENTS AND METHODS:EPIK-O was an open-label, phase III trial that randomly assigned patients with platinum-resistant/platinum-refractory HGSOC with no germline or known somatic BRCA mutation 1:1 to alpelisib 200 mg once daily + olaparib 200 mg twice daily or treatment of physician's choice (TPC; paclitaxel 80 mg/m2 once weekly or pegylated liposomal doxorubicin 40-50 mg/m2 once every 28 days). Patients had 1-3 previous systemic therapies. Previous bevacizumab was required (unless contraindicated); previous poly(adenosine diphosphate-ribose) polymerase inhibitors were allowed. Primary end point was progression-free survival (PFS) per RECIST 1.1 (blinded independent review committee [BIRC]). Secondary efficacy end points included overall response rate (ORR; per BIRC), duration of response (per BIRC), and overall survival (OS; key secondary end point). RESULTS:A total of 358 patients (alpelisib + olaparib [n = 180], TPC [n = 178]) were included. The median follow-up time was 9.3 months. At data cutoff (April 21, 2023), 33 (18.3%) and 30 (16.9%) patients remained on treatment with alpelisib + olaparib and TPC, respectively. The median PFS (BIRC) was 3.6 versus 3.9 months (hazard ratio [HR], 1.14 [95% CI, 0.88 to 1.48]; one-sided P = .84) for alpelisib + olaparib versus TPC. The ORR was 15.6% (95% CI, 10.6% to 21.7%) versus 13.5% (95% CI, 8.8% to 19.4%). The median OS was 10.0 versus 10.6 months (HR, 1.22; 95% CI, 0.87 to 1.71). The safety profile of alpelisib + olaparib was consistent with that observed for the individual agents. CONCLUSION:The primary objective, PFS improvement, was not met in EPIK-O. No new or unexpected adverse events were observed. Biomarker analyses provided new insights for responders to alpelisib + olaparib.

Background: Breast cancer (BC) is the most common type of cancer among women in Latin America. Evidence shows that delays in starting treatment, i.e. neoadjuvant chemotherapy or surgery, for early BC are associated with increased rates of relapse and mortality. Several factors have been associated with treatment delays such as socioeconomic status, health insurance type, age, racial/ethnic groups, educational level and rural residence among others. This study aimed to evaluate median days between diagnosis to first treatment and factors associated with delays in treatment initiation in patients diagnosed with early BC in Latin America. Methods: This sub-analysis included patients with stage I-III BC from the LATINA Breast (NCT04158258), a prospective, observational study that included patients diagnosed with BC between February 2020 to August 2022 in 31 centers from 10 countries in Latin America. Time interval was calculated from the BC biopsy date to the date of the first treatment administered, i.e. surgery or neoadjuvant chemotherapy or endocrine therapy. A multivariable logistic regression model was applied to evaluate factors associated with treatment delays of > 60 days after diagnosis. Results: From a total of 3275 patients included in the LATINA Breast registry, 2768 (84.5%) were diagnosed with stage I-III BC and were included in this sub-analysis. A total of 2516 patients (90.8%) had available information on the date of the diagnostic biopsy and initial treatment. Overall, the median number of days from diagnosis to first oncologic treatment was 55 days (IQR 28-97) and of them 1159 (46.1%) patients had >60 days from diagnosis to first treatment. Time interval from biopsy to treatment according to clinical stage were 46 days (IQR 20-99) for stage I, 57 days (IQR 28-99) for stage II, and 56 days (IQR 32-91) for stage III, (p=0.1578). Time interval from diagnosis to treatment according to first treatment received were 58 days (IQR 34-92) for neoadjuvant treatment and 46 days (IQR 19-99) for surgery, (p =0.2300). Time interval from diagnosis to treatment per country were: Argentina 48 days (IQR 8-88), Brazil 87 days (IQR 50-130), Chile 34 days (IQR 19-63), Colombia 67 days (IQR 33-101), Cuba 14.5 days (IQR 6-18), Dominican Republic 77 days (IQR 58.5-105.5), Guatemala 20.5 days (IQR 12-56), Mexico 34 days (IQR 22-47), Peru 46 days (IQR 19-84) and Uruguay 27 days (IQR 0-37). The time interval from diagnosis to treatment was higher in women treated in the public health system, 60 days (IQR 30-104) versus the private system, 45 days (IQR 24-77), (p <0.0001). Factors significantly associated with delays of >60 days from diagnosis to treatment were age >50 years (OR 1.41, 95% CI 1.15-1.74, p=0.0011), Black or African American/Brown (OR 3.3, 95% CI 1.15-1.74, p=0.0011), educational level illiterate/incomplete school (OR 1.42, 95% CI 1.06-1.89, p=0.0011) and public health insurance (OR 2.18, 95% CI 1.66-2.86, p<.0001). Conclusion: This analysis of the LATINA Breast study demonstrates that the median time from diagnosis to first treatment of early BC in Latin America is 55 days. Time intervals are variable among different countries likely reflecting differences in access to fragmented health care systems. Although in many countries, patients seem to be treated within an acceptable timeframe (<60 days), there is still a large population with long delays. Older patients, Black/African Americans/Brown, those with lower educational level and those treated within the public health care system, not surprisingly, had the longest timelines potentially impacting disease outcomes in these populations. Citation Format: Gustavo Werutsky, Paula Cabrera-Galeana, Heloisa Resende, Henry L. Gomez, Rosa Vasallo Veras, Miriam Raimondo, Ricardo Elías Brugés Maya, Maria del Rosario Vidal, Cynthia Villarreal-Garza, Yeni Nerón, Ana María Donoso, Fernanda B. Damian, José d'Oliveira Couto Filho, Felipe Cruz, Isabel Alonso, José Bines, Victoria Costanzo, Tomás Reinert, Juan Manuel Donaire, Adriana Elizabeth Borello, Eduardo Cronemberger, Luis Enrique Fein, Marcela Urrego, Enrique Alanya, Jorge Luis Soriano García, Saul Campos-Gomez, Eduardo A. Richardet, Hugo Castro-Salguero, Diego Gómez, Angel Hernández, Carlos Farfan, Ronald Rodríguez, Rafaela Gomes de Jesus, Carlos Barrios. Time Interval Between Diagnosis and Treatment of Early Breast Cancer and the Impact of Health Insurance Coverage in Latin America: A Sub Analysis of the LATINA Breast Study (LACOG 0615 / MO39485) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-08-07.

Importance:Ribociclib, 600 mg showed substantial survival benefits in patients with hormone receptor-positive (HR+)/ERRB2-negative (ERBB2-; formerly HER2) advanced breast cancer (ABC) in the phase 3 MONALEESA trials but was associated with dose-dependent adverse events (AEs) that were manageable with dose reductions. Objective:To investigate whether a 400-mg ribociclib starting dose could reduce the incidence of AEs while maintaining efficacy in ABC. Design, Setting, and Participants:The AMALEE phase 2, multicenter, randomized, open-label, interventional noninferiority study was conducted between June 18, 2019, and December 8, 2020, and included pre- and postmenopausal women with newly diagnosed HR+/ERBB2- ABC. The study was conducted across 107 sites in 23 countries (across Europe and Australia, Latin America, North America, and Asia). The data were analyzed at the final data cutoff (August 30, 2024). Interventions:Randomization 1:1 to ribociclib, 400 mg + a nonsteroidal aromatase inhibitor or ribociclib, 600 mg + a nonsteroidal aromatase inhibitor (premenopausal patients also received goserelin). Main Outcomes and Measures:Overall response rate (ORR; primary end point); ΔFridericia-corrected QT interval (QTcF) from baseline to cycle 1 day 15, 2 hours postdose (ΔQTcF; secondary end point); duration of response (DOR); time to response (TTR); progression-free survival (PFS); pharmacokinetics; and safety. Final analysis results are reported. Results:Baseline characteristics and prior anticancer therapy were balanced among the 376 patients (median [range] age, 58.0 [27-96] years). Median (range) follow-up from randomization was 53.5 (36.0-64.0) months (final data cutoff: August 30, 2024). The absolute ORR difference between ribociclib, 400 mg and ribociclib, 600 mg was -7.2% (ORR ratio, 0.87; 90% CI, 0.74-1.03). With ribociclib, 400 mg vs ribociclib, 600 mg, median PFS (26.9 vs 25.1 months) and DOR (26.5 vs 28.8 months) were similar; TTR was longer (13.1 vs 9.0 months). The maximal plasma concentration after dose and the 24-hour area under the curve (measured at the primary data cutoff) were 28.0% and 42.7% lower, respectively, with ribociclib, 400 mg than ribociclib, 600 mg. Ribociclib, 400 mg had a shorter ΔQTcF (12.5 vs 19.7 milliseconds at cycle 1 day 15, 2 hours postdose), lower grade 3 or4 neutropenia rate (41.0% vs 58.5%), and fewer patients who required dose reduction due to AEs (29 patients [15.4%] vs 69 patients [36.9%]). Liver-related AEs, kidney toxic effects, interstitial lung disease or pneumonitis, and AE-prompted discontinuation rates were similar between arms. Conclusions and Relevance:The AMALEE randomized clinical trial did not demonstrate ORR noninferiority of ribociclib, 400 mg vs ribociclib, 600 mg, with comparable DOR and PFS between doses. Ribociclib, 400 mg had longer TTR, lower pharmacokinetic exposure, and lower rates of QTcF prolongation and neutropenia. The final results confirmed the standard ribociclib, 600 mg starting dose in HR+/ERBB2- ABC while supporting dose reduction to manage dose-dependent AEs. Trial Registration:ClinicalTrials.gov Identifier: NCT03822468.

Ribociclib, 600 mg showed substantial survival benefits in patients with hormone receptor–positive (HR + )/ ERRB2 –negative ( ERBB2 − ; formerly HER2 ) advanced breast cancer (ABC) in the phase 3 MONALEESA trials but was associated with dose-dependent adverse events (AEs) that were manageable with dose reductions. To investigate whether a 400-mg ribociclib starting dose could reduce the incidence of AEs while maintaining efficacy in ABC. The AMALEE phase 2, multicenter, randomized, open-label, interventional noninferiority study was conducted between June 18, 2019, and December 8, 2020, and included pre- and postmenopausal women with newly diagnosed HR + / ERBB2 − ABC. The study was conducted across 107 sites in 23 countries (across Europe and Australia, Latin America, North America, and Asia). The data were analyzed at the final data cutoff (August 30, 2024). Randomization 1:1 to ribociclib, 400 mg + a nonsteroidal aromatase inhibitor or ribociclib, 600 mg + a nonsteroidal aromatase inhibitor (premenopausal patients also received goserelin). Overall response rate (ORR; primary end point); ΔFridericia-corrected QT interval (QTcF) from baseline to cycle 1 day 15, 2 hours postdose (ΔQTcF; secondary end point); duration of response (DOR); time to response (TTR); progression-free survival (PFS); pharmacokinetics; and safety. Final analysis results are reported. Baseline characteristics and prior anticancer therapy were balanced among the 376 patients (median [range] age, 58.0 [27-96] years). Median (range) follow-up from randomization was 53.5 (36.0-64.0) months (final data cutoff: August 30, 2024). The absolute ORR difference between ribociclib, 400 mg and ribociclib, 600 mg was −7.2% (ORR ratio, 0.87; 90% CI, 0.74-1.03). With ribociclib, 400 mg vs ribociclib, 600 mg, median PFS (26.9 vs 25.1 months) and DOR (26.5 vs 28.8 months) were similar; TTR was longer (13.1 vs 9.0 months). The maximal plasma concentration after dose and the 24-hour area under the curve (measured at the primary data cutoff) were 28.0% and 42.7% lower, respectively, with ribociclib, 400 mg than ribociclib, 600 mg. Ribociclib, 400 mg had a shorter ΔQTcF (12.5 vs 19.7 milliseconds at cycle 1 day 15, 2 hours postdose), lower grade 3 or4 neutropenia rate (41.0% vs 58.5%), and fewer patients who required dose reduction due to AEs (29 patients [15.4%] vs 69 patients [36.9%]). Liver-related AEs, kidney toxic effects, interstitial lung disease or pneumonitis, and AE-prompted discontinuation rates were similar between arms. The AMALEE randomized clinical trial did not demonstrate ORR noninferiority of ribociclib, 400 mg vs ribociclib, 600 mg, with comparable DOR and PFS between doses. Ribociclib, 400 mg had longer TTR, lower pharmacokinetic exposure, and lower rates of QTcF prolongation and neutropenia. The final results confirmed the standard ribociclib, 600 mg starting dose in HR + / ERBB2 − ABC while supporting dose reduction to manage dose-dependent AEs. ClinicalTrials.gov Identifier: NCT03822468

Bone health is central to the management of patients with metastatic castration-resistant prostate cancer (mCRPC). International guidelines recommend giving a bone-protecting agent (BPA) to patients with mCRPC and bone metastases. However, the data supporting these recommendations were generated before androgen receptor pathway inhibitors (ARPIs) were available. Here we publish for the first time fracture rates from an interim safety analysis of the international prospective phase 3 PEACE-3 trial comparing radium-223 (223Ra) combined with enzalutamide for first-line mCPRC to enzalutamide alone. After results from the ERA-223 trial (abiraterone ± 223Ra) showed a high fracture rate in both arms, the independent data monitoring committee of PEACE-3 mandated BPA use during the trial, which increased BPA use from 46.1% to 97%. For patients who received BPA therapy, fracture rates significantly decreased in both study arms. At 1 year, fractures decreased from 15.6% to 2.6% with a BPA in patients receiving enzalutamide monotherapy. The interim safety analysis of PEACE-3 underscores the high risk of fracture in patients with mCRPC and the necessity of complying with guidelines regarding BPA administration in the ARPI era.The EORTC GUCG-1333 PEACE-3 trial is registered on ClinicalTrials.gov as NCT02194842 and on EudraCT as 2014-001787-36.

Abstract Background: Breast cancer (BC) is the most common malignancy and one of the leading causes of cancer death in women in Latin America (LATAM). However, the region lacks a unified multinational initiative to investigate BC and to further understand regional disparities. Methods: LATINA (LACOG 0615/MO39485) is the first multinational prospective cohort study designed to describe clinicopathological characteristics, treatment patterns, and outcomes of patients with BC in LATAM. Patients aged ≥18 years diagnosed with primary or recurrent BC in the 12 months preceding site activation were included. Data were collected at enrollment and every 6 months for up to 5 years. We present here the results for clinicopathological and demographic characteristics at BC diagnosis. Multivariable logistic regression was performed to investigate characteristics associated with later diagnosis (stage II/III vs. stage I) and detection method (symptomatic vs. screening). Causal mediation analysis was performed to investigate the detection method as a mediator of the effect of health care provision (public or private) on stage at diagnosis. Results: Between February 2020 and August 2022, 3276 patients from 31 research sites in 10 LATAM countries were included. Most patients in this cohort (72.1%, N=2362) were treated in the public health system. Regarding ethnicity, most patients (91.8%, N=3008) self-identified as Latinos and were White (47.3%, N=1549), American Indian (21.0%, N=689), and Black or Brown (16.6%, N=544). The median age at diagnosis was 54 years (range 23–95), 41.8% (N=1368) were < 50 years of age at BC diagnosis, and 54.1% (N=375) of the American Indian patients were ≤50 years of age. BC subtype distribution was: 43.2% (N=1336) luminal A, 14.3% (N=433) luminal B, 22.9% (N=709) human epidermal growth factor receptor 2-positive (HER2+), and 15.4% (N=477) triple negative. In patients older than 50 years old, most cases were detected with symptoms, particularly in the public health system (63.2%, N=836) vs. 50.5% (N=232) in the private health system, p< 0.0001). This was also the case in Black/Brown (61.6%, N=178) and American Indian patients (89.5%, N=281) vs. White patients (45.6%, N=413) (p< 0.0001). In the public system, 37.7% (N=890) and 31.7% (N=748) of cases were diagnosed at stage II and III vs. 37.6% (N=343) and 26.6% (N=243) of cases in the private system, respectively (p< 0.0001). Users of the public health system had a significantly higher risk of being diagnosed with symptoms vs. screening (adjusted odds ratio [aOR] 3.54, 95% CI 2.17–5.76). Causal mediation analysis showed that the detection method (screening vs. symptomatic) mediated 21.8% (95% CI 1.7%–41.9%, p=0.034) of the effect of health care provision (public or private) on stage at diagnosis. Self-identifying as Black (aOR 2.11, 95% CI 1.29–3.45), age < 40 years (aOR 1.97, 95% CI 1.20–3.23), public health care provision (aOR 2.18, 95% CI 1.32–3.59), and a diagnosis of HER2+ (aOR 1.74, 95% CI 1.20–2.52) or triple-negative BC (aOR 2.34, 95% CI 1.47–3.71) were associated with an increased risk of being diagnosed at a later stage. Conclusions: A significant proportion of new BC diagnoses in LATAM is observed in patients < 50 years of age. Reflecting the low screening coverage throughout the region, most patients detect the disease with symptoms. Stage III BC accounted for 30.3% of new cases, being more common among users of the public health system. Differences in the stage at diagnosis related to health care provision (public or private), ethnicity, and country underscore significant disparities that need to be addressed. Further analyses of these data will help identify factors associated with late diagnosis and support the development of regional corrective health policies. Citation Format: Gustavo Werutsky, Cynthia Villarreal-Garza, Henry Gómez, Juan Manuel Donaire, José Bines, Luis Henrique Fein, Maria Clara Horsburgh, Paula Cabrera-Galeana, Heloísa Resende, Rosa Vasallo Veras, Miriam Raimondo, Ricardo Elías Brugés Maya, Vidal Maria Del Rosario, Yeni Nerón, Ana Maria Donoso, Fernanda B. Damian, José D'Oliveira, Couto Filho, Maria Isabel Alonso, Victoria Costanzo, Tomás Reinert, Adriana Elizabeth Borello, Eduardo Cronenberger, Luis Fein, Marcela Urrego, Enrique Alanya, Jorge Luis Soriano García, Saúl Campos-Gomez, Eduardo A. Richardet, Hugo Castro-Salguero, Felipe Cruz, Diego Gómez, Angel Hernández, Carlos Alberto Farfan Tello, Ronald Rodríguez, Rafaela Jesus, Gustavo Gössling, Carlos Barrios. Clinicopathological Characteristics and Factors Associated With Screening and Late-Stage Diagnosis in Patients With Breast Cancer in Latin America: The LATINA Study (LACOG 0615/MO39485) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-04.

Background Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment.Patients and Methods Patients with nmCRPC were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval-specific new and cumulative event rates were determined during the first 24 months of the double-blind period.Results Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and <= 2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months.Conclusion Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment-related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment.Trial number ClinicalTrials.gov identifier NCT02200614 This report examines darolutamide tolerability from extended follow-up for both the double-blind and open-label treatment periods of the phase III ARAMIS trial and characterizes the onset and occurrence over time of treatment-emergent adverse events of interest, including those commonly associated with androgen receptor inhibitor therapy and androgen-suppressive treatment.

Abstract Background: Breast cancer (BC) is the most common malignancy and one of the leading causes of cancer death in women in Latin America (LATAM). Studies have highlighted the importance of understanding contextual characteristics of each patient population to inform health policy-making. However, few data are available on women from LATAM, a region with marked inequalities. Methods: LATINA (LACOG 0615/MO39485) is a multicenter prospective cohort study designed to describe sociodemographic characteristics, diagnosis, treatment, and outcomes of patients with BC in LATAM. Female and male patients aged ≥18 years newly diagnosed (i.e., < 12 months from research site activation) histologically confirmed clinical stage I-IV BC were enrolled. Eligible patients provided informed consent and had data collected from medical records at diagnosis and every 6 months up to 5 years. Results: Between February 2020 and August 2022, 3276 patients with BC from 31 research sites in 10 LATAM countries were included. Median age was 54 years (range 23–95), 91.8% (N=3008) were Hispanic or Latinos, the majority (68%, N=2224) were diagnosed with stage II or III BC, and 73% (N=2362) were treated in the public health system. Age, stage and detection method stratified by education level, marital status and employment status are shown in Table 1. Overall, 38.8% (N=1149) of patients had not completed high school. These patients were more frequently diagnosed by symptoms and diagnosed at later stages than those who had completed high school or college. Half of the patients were married/in a civil partnership at BC diagnosis (50.5%, N=1497). Unmarried patients were more commonly diagnosed by symptoms (71.7%, N=835 vs. 64%, N=916, p< 0.001) and with stage II/III BC (71.4%, N=868 vs. 67.6%, N=1038, p< 0.001) than married patients. Most patients (54.1%, N=1603) were not employed at BC diagnosis. Patients not employed were more frequently diagnosed by symptoms (68.8%, N=1044) than employees/self-employed (61.6%, N=675). After adjusting for age, country, health care provision (public or private), stage, and BC subtype, being diagnosed by symptoms was associated with not being married (adjusted odds ratio [aOR] 1.41, 95% CI 1.11–1.82, p=0.004), being not employed (aOR 1.41, 95% CI 1.08–1.84, p=0.011), and not having completed high school (aOR 1.46, 95% CI 1.00–2.13, p=0.031). Conclusions: Patients with a lower level of education, unmarried and not employed, are more likely not to perform BC screening and to be diagnosed by symptoms. Socioeconomic characteristics impact the method of detection of BC in LATAM and are associated with diagnosis at later stages. Further analyses of the LATINA study will provide invaluable data for informing regional health policy-making in LATAM. Citation Format: Gustavo Werutsky, Cynthia Villarreal-Garza, Henry Gómez, Juan Manuel Donaire, José Bines, Luis Henrique Fein, Maria Clara Horsburgh, Paula Cabrera-Galeana, Heloísa Resende, Rosa Vasallo Veras, Miriam Raimondo, Ricardo Elías Brugés Maya, Vidal Maria Del Rosario, Yeni Nerón, Ana Maria Donoso, Fernanda B. Damian, José D'Oliveira, Couto Filho, Maria Isabel Alonso, Victoria Costanzo, Tomás Reinert, Adriana Elizabeth Borello, Eduardo Cronenberger, Luis Fein, Marcela Urrego, Enrique Alanya, Jorge Luis Soriano García, Saúl Campos-Gomez, Eduardo A. Richardet, Hugo Castro-Salguero, Felipe Cruz, Diego Gómez, Angel Hernández, Carlos Alberto Farfan Tello, Ronald Rodríguez, Rafaela Jesus, Gustavo Gössling, Carlos Barrios. The Impact of Socioeconomic Factors on Breast Cancer Diagnosis in Latin America: The LATINA study (LACOG 0615/MO39485) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-05.

ABSTRACT BACKGROUND: Patients with chronic renal disease and undergoing hemodialysis are at a high risk for developing several complications. Fatigue is a common, troubling symptom that affects such patients and can contribute to unfavorable outcomes and high mortality. OBJECTIVE: This cross-sectional study aimed to evaluate the prevalence of fatigue in Brazilian patients with chronic kidney disease undergoing hemodialysis and determine the predisposing factors for fatigue. DESIGN AND SETTING: An observational, cross-sectional, descriptive study was conducted in two renal replacement therapy centers in the Greater ABC region of São Paulo. METHODS: This study included 95 patients undergoing dialysis who were consecutively treated at two Brazilian renal replacement therapy centers between September 2019 and February 2020. The Chalder questionnaire was used to evaluate fatigue. Clinical, sociodemographic, and laboratory data of the patients were recorded, and the Short Form 36 Health Survey, Pittsburgh Sleep Quality Index, and Beck Depression Inventory were administered. RESULTS: The prevalence of fatigue in patients undergoing hemodialysis was 51.6%. Fatigue was independently associated with lower quality of life in terms of physical and general health. Patients with fatigue had a higher incidence of depression (65.9% vs. 34.1%, P = 0.001) and worse sleep quality (59.1% vs. 49.9%; P = 0.027) than those without fatigue. CONCLUSION: Prevalence of fatigue is high in patients undergoing hemodialysis and is directly related to physical and general health.

BACKGROUND In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival. METHODS We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability). RESULTS A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). CONCLUSIONS Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

Aim: Darolutamide significantly improved metastasis-free survival (MFS) and overall survival (OS) versus placebo in the phase III ARAMIS study. We evaluated outcomes in Black/African-American patients in ARAMIS. Materials & methods: Patients with nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554) plus androgen-deprivation therapy. The primary end point was MFS. Secondary end points included OS and safety. Results: In 52 (3.4%) Black/African-American patients, darolutamide improved MFS (median: not reached vs 12.4 months) and OS (3-year survival rates: 100 vs 71%) versus placebo. The safety profile of darolutamide in Black/African-American patients was consistent with that of all ARAMIS patients. Conclusion: In Black/African-American patients, darolutamide improved MFS and OS and was well tolerated, consistent with the overall ARAMIS population.

PURPOSE For patients with metastatic hormone-sensitive prostate cancer, metastatic burden affects outcome. We examined efficacy and safety from the ARASENS trial for subgroups by disease volume and risk. METHODS Patients with metastatic hormone-sensitive prostate cancer were randomly assigned to darolutamide or placebo plus androgen-deprivation therapy and docetaxel. High-volume disease was defined as visceral metastases and/or ≥ 4 bone metastases with ≥ 1 beyond the vertebral column/pelvis. High-risk disease was defined as ≥ 2 risk factors: Gleason score ≥ 8, ≥ 3 bone lesions, and presence of measurable visceral metastases. RESULTS Of 1,305 patients, 1,005 (77%) had high-volume disease and 912 (70%) had high-risk disease. Darolutamide increased overall survival (OS) versus placebo in patients with high-volume (hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.82), high-risk (HR, 0.71; 95% CI, 0.58 to 0.86), and low-risk disease (HR, 0.62; 95% CI, 0.42 to 0.90), and in the smaller low-volume subgroup, the results were also suggestive of survival benefit (HR, 0.68; 95% CI, 0.41 to 1.13). Darolutamide improved clinically relevant secondary end points of time to castration-resistant prostate cancer and subsequent systemic antineoplastic therapy versus placebo in all disease volume and risk subgroups. Adverse events (AEs) were similar between treatment groups across subgroups. Grade 3 or 4 AEs occurred in 64.9% of darolutamide patients versus 64.2% of placebo patients in the high-volume subgroup and 70.1% versus 61.1% in the low-volume subgroup. Among the most common AEs, many were known toxicities related to docetaxel. CONCLUSION In patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel increased OS with a similar AE profile in the subgroups, consistent with the overall population. [Media: see text]

Objective To evaluate the prognostic impact of the parameters of myocardial deformation using three-dimensional speckle tracking echocardiography (3DSTE) in patients with breast cancer who underwent chemotherapy with low doses of anthracyclines. Background Chemotherapy-related cardiotoxicity has an important prognostic impact on cancer survivors. Three-dimensional STE has revealed more consistent data than two-dimensional techniques and may represent a more accurate tool in the evaluation of myocardial function in patients who underwent chemotherapy. Methods We evaluated patients with breast cancer who were treated with anthracyclines (associated or not with trastuzumab) in five stages: baseline, after cumulative doses of 120 and 240 mg/m2 of doxorubicin, and then, after 6 months and at least 1 year after anthracyclines. Ultrasensitive troponin I (US-TnI) and a standard echocardiography study were performed at each stage. We analyzed left ventricular ejection fraction (LVEF) by Simpson's method, two-dimensional speckle tracking (2DSTE) with longitudinal and radial strain values, and 3DSTE with longitudinal, radial, and circumferential strain as well as twist, torsion, rotation, and three-dimensional global area strain (3DGAS). Cardiotoxicity was defined as a decrease in LVEF by more than 10 percentage points to a value lower than 53%. Results We evaluated 51 female patients who were aged 50.6 ± 11 years. After the cumulative dose of 240 mg/m2 of doxorubicin, US-TnI was increased (>34 pg/ml) in 21 patients (45%, p > 0.001), LVEF remained unchanged (p = 0.178), while 2DSTE longitudinal strain was decreased (from −17.8% to −17.1%, p < 0.001) and 3DSTE detected changes in longitudinal, radial, circumferential, and area strain. After a lower cumulative dose of doxorubicin (120 mg/m2), 3DGAS (p < 0.001) was the only parameter that was changed. In the follow-up, 7 (13%) patients presented a decrease in LVEF. Three-dimensional GAS early changed to abnormal values was the only variable associated with a subsequent decrease in LVEF (definitive cardiotoxicity). Conclusion In patients with breast cancer, 3DSTE detected early changes in area strain after very low doses of doxorubicin. The 3DGAS early changed to abnormal values was associated with a subsequent decrease in LVEF, representing a promising technique to predict chemotherapy-induced cardiomyopathy.