Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.

PURPOSE: Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma. METHODS: Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses. RESULTS: In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02. CONCLUSION: The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.

Expanded Access Study of Palbociclib Plus Letrozole for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer in Latin America for Whom Letrozole Therapy is Deemed Appropriate.

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.

This study was done to learn more about the safety of 2 medicines together for women with advanced breast cancer after menopause. All 130 women in the study had the most common kind of breast cancer and were from Argentina, Brazil, Colombia, and Mexico. Everyone took 2 oral medicines called palbociclib and letrozole during the study. The researchers looked for any side effects experienced by the women while taking these medicines together. Another goal of the study was to see how well the treatment worked. Blood tests showed 70.0% of women had a side effect where they had a lower number of a type of white blood cell called a neutrophil. In total, 34.6% of women had low levels of another white blood cell called a leukocyte. These blood test results can mean a person is more likely to get infections. Serious side effects were experienced by 24.6% of the women, which meant these were life-threatening, caused lasting problems, or they needed hospital care. To cope with their side effects, 22.3% of the women switched to a lower palbociclib dose; 24.8% of the women had an overall response, which meant they either had a decrease in their tumor size or all cancer signs disappeared from their body. The most common length of time in the study was 10.6 months and the longest time was 29.3 months. The results of this study support using palbociclib plus letrozole to treat women who live in Latin America with advanced breast cancer after menopause.

Tratamiento de Superficie utilizados en Microtornillos de Ortodoncia y su Efecto en la Estabilidad Primaria y Secundaria: Revisión Bibliográfica

Resumen: Los microtornillos de ortodoncia corresponden a dispositivos de anclaje temporal que sirven como coadyuvantes en el tratamiento ortodóncico y cuyo uso se ha ido incrementando en el último tiempo. Las fallas de los microtornillos tienden a ocurrir durante la primera semana de inserción por lo que mejorar la estabilidad es un paso importante para mejorar la confiabilidad del tratamiento. Una posible solución a esto es modificar la superficie del microtornillo. Objetivo: Identificar en la literatura actual los tratamientos de superficie más utilizados que favorezcan la estabilidad primaria y secundaria en el éxito de los microtornillos en ortodoncia. Material y método: Se realizó una búsqueda en Pubmed y EBSCO con los términos en idioma inglés "miniscrew"/"mini implant" AND "surface", "treatment" and "stability". Se incluyeron los estudios realizados in vivo con el objetivo de comparar y/o evaluar el efecto de los tratamientos realizados en la superficie del microtornillo en el éxito o estabilidad de éste, artículos disponibles en inglés y español. Se excluyeron estudios realizados en implantes dentales y/o médicos, in vitro, estudios clínicos sin grupo control. Resultados: 25 publicaciones fueron utilizadas en la revisión, habiendo 11 tipos de tratamiento de superficie estudiados. La generación de ma trices de nanotubos de óxido de titanio, fotofuncionalización mediada por rayos ultravioleta y anodizado de superficie evidenciaron aumento de la estabilidad de los microtornillos. El uso de técnicas convencionales: grabado ácido, arenado-grabado ácido, no es concluyente en cuanto a su efecto en la estabilidad. Conclusión: Hay escasa evidencia sobre los tratamientos de superficie realizados en microtornillos de ortodoncia para la mejora de su estabilidad. Técnicas pioneras como la generación de matrices de nanotubos de óxido de titanio, fotofuncionalización mediada por rayos ultravioleta y anodizado de superficie evidenciaron aumento de la estabilidad de los microtornillos, siendo necesaria la replicación de los estudios en humanos. La utilización de técnicas convencionales tales como grabado ácido y arenado-grabado ácido, no es concluyente en cuanto a su efecto en la estabilidad de los microtornillos.

Abstract: Orthodontic miniscrews are temporary anchoring devices that help as adjuvants in orthodontic treatment and whose use has increased in recent times. Miniscrew failures can happen during the first week of insertion, so improving stability is an important step to enhance treatment reliability. A possible solution to this issue is to modify the miniscrew surface. Objective: To identify in the current literature the most widely used surface treatments that favor the primary and secondary stability and success of orthodontic miniscrews. Material and method: A search was made in Pubmed and EBSCO with the English terms "miniscrew"/"mini implant" AND "surface", "treatment" and "stability". In vivo studies were included with the aim of comparing and/or evaluating the effect of the treatments performed on the miniscrew's surface and their success or stability, articles available in English and Spanish. Studies performed in dental and/or medical implants, in vitro, clinical studies without control group were excluded. Results: 25 publications were used in the review, with 11 types of surface treatment studied. The generation of titanium oxide nanotube matrices, ultraviolet-mediated photofunctionalization and surface anodizing showed an increase in the stability of the miniscrews. The use of conventional techniques: acid etching, sandblasting-acid etching, is inconclusive as to its effect on stability. Conclusion: There is little evidence of surface treatments performed on orthodontic miniscrews to improve their stability. Pioneering techniques such as the generation of titanium oxide nanotube matrices, ultraviolet-mediated photofunctionalization and surface anodizing showed increased stability of the miniscrews, and require their replication on human studies. The use of conventional techniques such as acid etching and acid sandblasting-etching is inconclusive as to its effect on the stability of the miniscrews.

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer.

BACKGROUND: In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. METHODS: Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1-16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. RESULTS: Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77-13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08-12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. CONCLUSIONS: Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.

Impact of hydronephrosis and kidney function on survival in newly diagnosed advanced cervical cancer.

OBJECTIVES: To assess the impact of hydronephrosis and kidney function in newly diagnosed advanced cervical cancer patients. METHODS: A retrospective cohort study of newly diagnosed cervical cancer stage IIIB to IVB was conducted in a tertiary hospital in Brazil. Data from clinical records between 2014 and 2018 were reviewed. RESULTS: A total of 285 women with advanced cervical cancer and no previous cancer treatment were included. 108 (37.9%) patients were diagnosed with hydronephrosis (HN) before or during the first treatment, 49 (17.2%) patients underwent ureteral obstruction relief, and emergency hemodialysis was performed in 17 patients due to uremia. The median overall survival (mOS) was 46.9 months for non-HN, 19.2 months for unilateral-HN, and 10.0 months for bilateral-HN (non-HN vs HN-groups, p = 0.0001). Patients with eGFR >= 60 mL/min/1.73 m2, before or during the first cancer treatment, had mOS of 46.9 months, 23.5 months, and 11.1 months for non-HN, unilateral-HN and bilateral-HN, respectively (non-HN vs bilateral-HN, p = 0.002). Patients with eGFR < 60 mL/min/1.73 m2 had mOS 23.4 months, 19.2 months, and 10.0 months for non-HN, unilateral-HN and bilateral-HN, respectively (non-HN vs bilateral-HN, p = 0.003). In the HN group, mOS was 11.2 months among those who underwent urinary diversion and 15.6 months among those who did not; p = 0.2. On multivariate analysis, cancer treatment, FIGO stage, and HN were prognostic factors for OS; however eGFR < 60 mL/min/1.73 m2 does not appear to be associated with worse survival by itself (p = 0.7). CONCLUSION: HN seems to have a negative effect on survival of patients with cervical cancer even after adjustment for FIGO stage and cancer treatment. The mOS does not appear to be worse in patients with HN who required urinary diversion compared to those who did not.

Survival with Cemiplimab in Recurrent Cervical Cancer.

BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.