The University of Texas Southwestern Medical Center

THURSDAY, Feb. 6, 2025 -- For patients with high-risk, early-stage estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer (BC), adding nivolumab to neoadjuvant chemotherapy increases pathological complete response (pCR) rates, according to a study published online Jan. 21 in Nature Medicine . Sherene Loi, M.B.B.S., Ph.D., from the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues examined the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10 percent) ER-positive/HER2-negative primary BC in a randomized, multicenter, phase 3 trial involving 510 patients. Participants were randomly allocated to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo. The researchers found that compared with placebo, the nivolumab arm had a significantly higher primary end point of pCR (24.5 versus 13.8 percent), with greater benefit seen for those with programmed death ligand 1-positive tumors (44.3 versus 20.2 percent). No new safety signals were identified. Five deaths occurred in the nivolumab arm, two of which were related to study drug toxicity, while there were no deaths reported in the placebo arm. "We hope that these results inform treatment decisions and, in turn, improve outcomes for patients with breast cancer, ultimately improving cure rates," coauthor Heather McArthur, M.D., M.P.H., from the University of Texas Southwestern Medical Center in Dallas, said in a statement. Several authors disclosed ties to pharmaceutical companies, including Bristol Myers Squibb, which manufactures nivolumab and funded the study. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

THURSDAY, Dec. 5, 2024 -- The impact of socioeconomic factors on disease activity in rheumatoid arthritis (RA) varies by academic or safety net hospital setting, according to a study published online Oct. 18 in ACR Open Rheumatology. Joseph Kim, M.D., from the University of Texas Southwestern Medical Center in Dallas, and colleagues analyzed the impact of the Area Deprivation Index (ADI) on disease activity and cardiovascular comorbidity in RA. The analysis included data from 542 patients seen at an academic practice and 496 treated at a safety net hospital. The researchers found that in the academic cohort, compared with those with low ADI scores (<3, less deprivation), those with high ADI scores (>8, more deprivation) had higher RA disease activity scores, as measured by the Routine Assessment of Patient Index and the Clinical Disease Activity Index, and more functional impairment, as measured by the Multidimensional Health Assessment Questionnaire, lower MyChart use, and different smoking history. The only significant difference seen in the safety net cohort was for smoking status. "The absence of differences in RA disease activity and functional impairment in patients suggests that the ADI may not be as effective at predicting RA disease activity specifically in a safety net health care context," the authors write. "Identifying the discrepancies between the two systems may elucidate areas of improvement for patient care." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

For the second time in five years, an FDA advisory committee voted against endorsing the benefit-risk profile of Lexicon’s drug sotagliflozin. The Endocrinologic and Metabolic Drugs Advisory Committee voted 11-3 against the drug, an SGLT2 inhibitor the company has proposed as an adjunct to insulin to improve glycemic control in adults with type 1 diabetes and chronic kidney disease. The same adcomm in January 2019 voted 8-8 on the benefit-risk profile of sotagliflozin in type 1 diabetes, and the FDA rejected the application about three months later, saying it found an unacceptable level of risk of diabetic ketoacidosis (DKA) compared with the drug’s benefit. Kicking off the meeting, Lexicon CMO Craig Granowitz explained that the indication the company is seeking is a slight tweak from the last time around, this time for a “high-risk population where the benefit-risk assessment is different” than type 1 diabetics. FDA’s Justin Penzenstadler presented part of the agency’s side, discussing how the available data “do not provide reassurance that the magnitude of the DKA risk observed” in the clinical trial program applies to patients with type 1 diabetes and chronic kidney disease. Committee members voting against Lexicon questioned whether there were enough new data. Panelist Prabir Roy-Chaudhury, co-director of the University of North Carolina Kidney Center, was one of three votes in favor of sotagliflozin because he said he thinks “it’s important to live in a big bubble, and I do believe risk mitigation strategies will work.” Earlier in the day, following the FDA’s and Lexicon’s presentations, committee members’ discussions generally expressed uncertainties on DKA risks and the magnitude of clinical benefit. Committee panelist Thomas Wang of the University of Texas Southwestern Medical Center said he didn’t see enough new prospective data from Lexicon. There’s an unmet clinical need but there’s so much uncertainty on the benefit and risk side, he said. The FDA in its briefing documents similarly raised repeat safety and efficacy questions , questioning the use of post-hoc analyses from three Phase 3 clinical trials. Since the rejection five years ago, the FDA and Lexicon have gone back and forth over a path forward in type 1 diabetes. In May 2022, the drug was approved for use in adults with type 2 diabetes who have chronic kidney disease and other cardiovascular risk factors, to reduce the risk of cardiovascular death, hospitalization for heart failure and urgent heart failure visits. It’s sold under the brand name Inpefa. In December, the FDA told Lexicon that for the new indication it needed to provide a rationale for its proposed chronic kidney disease population, “with statistically and clinically meaningful evidence of glycemic control.” The FDA often follows the advice of its adcomms although it isn’t required to.