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1.
Eur J Cancer ; 205: 114103, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729054

RESUMO

BACKGROUND: PTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel. METHODS: This double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥ 18 years with progressing mCRPC and performance status 0-2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160 mg orally, once daily) with capivasertib (400 mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥ 50 % PSA decrease from baseline, or circulating tumor cell count conversion (from ≥ 5 at baseline to < 5 cells/7.5 mL). Subgroup analyses by PTENIHC status were pre-planned. RESULTS: Overall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1 %) enzalutamide/capivasertib and 9/48 (18.8 %) enzalutamide/placebo (absolute difference 0.4 % 90 %CI -12.8 to 13.6, p = 0.58), with similar results in the PTENIHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTENIHC loss (10.1 months [95 %CI: 4.6-13.9] vs 14.8 months [95 %CI: 10.8-18]; p = 0.02). Most common treatment-emergent grade ≥ 3 adverse events for the combination were diarrhea (13 % vs 2 %) and fatigue (10 % vs 6 %). CONCLUSIONS: Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Docetaxel , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Pirimidinas , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Feniltioidantoína/administração & dosagem , Feniltioidantoína/uso terapêutico , Feniltioidantoína/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pessoa de Meia-Idade , Método Duplo-Cego , Pirimidinas/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Androstenos/uso terapêutico , Androstenos/administração & dosagem , Idoso de 80 Anos ou mais , Pirróis
2.
JCO Clin Cancer Inform ; 4: 657-665, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32716647

RESUMO

PURPOSE: While there are studies under way to characterize the direct effects of the COVID-19 pandemic on the care of patients with cancer, there have been few quantitative reports of the impact that efforts to control the pandemic have had on the normal course of cancer diagnosis and treatment encounters. METHODS: We used the TriNetX platform to analyze 20 health care institutions that have relevant, up-to-date encounter data. Using this COVID and Cancer Research Network (CCRN), we compared cancer cohorts identified by querying encounter data pre-COVID (January 2019-April 2019) and current (January 2020-April 2020). Cohorts were generated for all patients with neoplasms (malignant, benign, in situ, and of unspecified behavior), with new incidence neoplasms (first encounter), with exclusively malignant neoplasms, and with new incidence malignant neoplasms. Data from a UK institution were similarly analyzed. Additional analyses were performed on patients with selected cancers, as well as on those having had cancer screening. RESULTS: Clear trends were identified that suggest a significant decline in all current cohorts explored, with April 2020 displaying the largest decrease in the number of patients with cancer having encounters. Of the cancer types analyzed, lung, colorectal, and hematologic cancer cohorts exhibited smaller decreases in size in April 2020 versus 2019 (-39.1%, -39.9%, -39.1%, respectively) compared with cohort size decreases for breast cancer, prostate cancer, and melanoma (-47.7%, -49.1%, -51.8%, respectively). In addition, cancer screenings declined drastically, with breast cancer screenings dropping by -89.2% and colorectal cancer screenings by -84.5%. CONCLUSION: Trends seen in the CCRN clearly suggest a significant decrease in all cancer-related patient encounters as a result of the pandemic. The steep decreases in cancer screening and patients with a new incidence of cancer suggest the possibility of a future increase in patients with later-stage cancer being seen initially as well as an increased demand for cancer screening procedures as delayed tests are rescheduled.


Assuntos
Infecções por Coronavirus/epidemiologia , Detecção Precoce de Câncer/tendências , Neoplasias/classificação , Neoplasias/epidemiologia , Pneumonia Viral/epidemiologia , COVID-19 , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pandemias , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
3.
BMJ Case Rep ; 13(5)2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32430351

RESUMO

This is a case report of a 67-year-old patient with castration resistant metastatic prostate cancer who developed an immune-mediated large vessel vasculitis following treatment with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1).


Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/diagnóstico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Humanos , Ipilimumab/efeitos adversos , Masculino , Nivolumabe/efeitos adversos , Vasculite/tratamento farmacológico
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