Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer.

Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with AKT1, CTNNB1 and ESR1 hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414.

Trends in adolescent COVID-19 vaccination receipt and parental intent to vaccinate their adolescent children, United States, July to October, 2021.

INTRODUCTION: There was a five-fold increase in COVID-19 hospitalization case counts among children and adolescents between June and October 2021. However, polls suggest that adolescent COVID-19 vaccination coverage has plateaued in the United States. METHODS: Using the Census Bureau's Household Pulse Survey, we assessed trends in COVID-19 vaccination among adolescents ages 12-17 years, parents' intention to vaccinate their adolescent children, and their reasons for not intending to vaccinate their children from July to October 2021 using a large, nationally representative survey of U.S. households (n = 59,424). Trends in COVID-19 adolescent vaccination coverage, nationally and by sociodemographic characteristics, factors associated with adolescent vaccination status and parental intent to vaccinate their adolescent children, as well as changes in reasons for non-vaccination were examined using regression models. RESULTS: Receipt of ≥1 dose of a COVID-19 vaccine among adolescents ages 12-17 years increased five percentage points, from 56% (July) to 61% (October), with significant increases across most sociodemographic variables. However, there were no significant changes in parental intention to vaccinate their adolescent children during the same time period. Approximately one-quarter of parents were unsure about or reluctant to vaccinate their children, which remained consistent from July to October. Among those who had not vaccinated their children, lack of trust in the government and vaccines, and the belief that the COVID-19 vaccine is not needed or effective, was higher in October compared to July. CONCLUSIONS: Parental intention to vaccinate their children has remained relatively stable throughout the late summer and early fall of 2021. Encouraging paediatricians to discuss the importance and safety of COVID-19 vaccines, addressing concerns and misinformation, as well as recommending and offering vaccines are important for increasing parental confidence in vaccines as well as vaccination uptake among adolescents.KEY MESSAGEReceipt of ≥1 dose of a COVID-19 vaccine among adolescents ages 12-17 years increased five percentage points, from 56% (July) to 61% (October), with significant increases across most sociodemographic variables.Approximately one quarter of parents were unsure about or reluctant to vaccinate their children, which remained consistent from July to October.Encouraging paediatricians to discuss the importance and safety of COVID-19 vaccines, addressing concerns and misinformation, as well as recommending and offering vaccines is important for increasing parental confidence in vaccines as well as vaccination uptake among adolescents.

Trends in COVID-19 vaccination receipt and intention to vaccinate, United States, April to August, 2021.

To assess trends in and factors associated with COVID-19 vaccination coverage, data from the Household Pulse Survey were analyzed. From April to August 2021, vaccination coverage with at least 1 dose increased from 70%-82%, while vaccination intent increased from 82%-86%, with the highest increase among the most vulnerable groups. More efforts are needed to boost confidence in vaccines and to encourage all eligible people to be fully vaccinated.