Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

The role of payment and financing in achieving health equity

Objective

The aim was to identify healthcare payment and financing reforms to promote health equity and ways that the Agency for Healthcare Research and Quality (AHRQ) may promote those reforms.

Data Sources and Study Setting

AHRQ convened a payment and financing workgroup–the authors of this paper–as part of its Health Equity Summit held in July 2022. This workgroup drew from its collective experience with healthcare payment and financing reform, as well as feedback from participants in a session at the Health Equity Summit, to identify the evidence base and promising paths for reforms to promote health equity.

Study Design

The payment and financing workgroup developed an outline of reforms to promote health equity, presented the outline to participants in the payment and financing session of the July 2022 AHRQ Health Equity Summit, and integrated feedback from the participants.

Data Collection/Extraction Methods

This paper did not require novel data collection; the authors collected the data from the existing evidence base.

Principal Findings

The paper outlines root causes of health inequity and corresponding potential reforms in five domains: (1) the differential distribution of resources between healthcare providers serving different communities, (2) scarcity of financing for populations most in need, (3) lack of integration/accountability, (4) patient cost barriers to care, and (5) bias in provider behavior and diagnostic tools.

Conclusions

Additional research is necessary to determine whether the proposed reforms are effective in promoting health equity.