Articles related to CLINICAL TRIALS

To date, FDA has approved three next-generation AR inhibitors for nonmetastatic CRPC: apalutamide, enzalutamide, and darolutamide. All three agents improve metastasis-free survival and overall survival. Selection of treatment can be guided by factors such as the patient’s overall health and frailty, potential drug-drug interactions, and the safety profile associated with each agent. This review summarizes the data from the practice-changing SPARTAN, PROSPER, and ARAMIS trials and provides insights on implementation in practice and promotes early intervention with AR inhibitors as standard of care for patients with high-risk nonmetastatic CRPC.

In patients with NETs with distant metastasis, 90Y radioembolization (90Y RE) might be an important treatment option; however, data to support clinical benefits are scarce. The authors purposed to analyze the use of 90Y RE in NET patients with hepatic metastases in an international, multicenter retrospective analysis. In reviewing response data, they conclude that 90Y RE could be an important alternative to peptide receptor radionuclide therapy as second-line treatment in patients with progressive liver-dominant disease pretreated with somatostatin analogs.

Following treatment of the 40 study patients with bevacizumab and atezolizumab, OS was observed in 4 patients with pNETs (20%) and 3 patients with epNETs (15%). The PFS was 14.9 months and 14.2 months in these cohorts, respectively. The findings suggest that clinical responses in patients with NET may follow treatment with the combination of bevacizumab and atezolizumab, with a PFS consistent with effective therapies.

The authors investigated expression of PD-L1 and V-domain Ig-containing suppressor of T cell activation (VISTA) in ACC and their associations with clinicopathological features and survival outcomes. They report that a higher VISTA expression intensity, a larger area, and a higher immunoscore were associated with increased risks of disease progression and overall mortality. However, PD-L1 expression in tumor cells or tumor-infiltrating immune cells was not associated with OS or DFS. The study points to the potential value of VISTA, in addition to PD-L1, as an immunotherapeutic target in ACC.

In the study,155 FDA-approved drugs with 136 potentially targetable genes were identified.One-hundred forty-six (94%) of the drugs showed no or low genetically predicted drug response. Although ATC-carrying BRAF mutations can benefit from BRAF inhibitors and this effect might be enhanced by a combined strategy including PIK3CA inhibitors in some of the patients, alterations in BRAFWT ATC are not directly targeted by currently FDA-approved options.

Hutchmed’s submission was based primarily on two phase 3 trials conducted in China. Even though a bridging study conducted in the US that suggested safety and efficacy similar to that observed in the Chinese study population, FDA responded that a multiregional clinical trial “more representative of the US patient population and in accordance with US medical practice will be required” for resubmission.