US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer.

PURPOSE: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET). PATIENTS AND METHODS: Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2- advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator's choice of ET (n = 239). RESULTS: In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = .0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1-mut subgroup. PFS also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = .0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1-mut subgroup. More patients who received elacestrant experienced nausea, vomiting, and dyslipidemia. CONCLUSION: The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.

FDA Approval Summary: Pembrolizumab, Atezolizumab, and Cemiplimab-rwlc as Single Agents for First-Line Treatment of Advanced/Metastatic PD-L1-High NSCLC.

FDA's approval of cemiplimab-rwlc on February 22, 2021, follows prior approvals of pembrolizumab and atezolizumab for similar indications as first-line treatment for patients with programmed death ligand-1 (PD-L1)-high advanced non-small cell lung cancer (NSCLC). Approvals of these anti-PD-L1 agents were supported by statistically significant and clinically meaningful improvements in overall survival (OS) in international, multicenter, active-controlled randomized trials. In KEYNOTE-024, the OS HR was 0.60 [95% confidence interval (CI), 0.41-0.89; P = 0.005] favoring pembrolizumab over platinum-doublet chemotherapy. In IMpower110, the OS HR was 0.59 (95% CI, 0.40-0.89; P = 0.0106) favoring atezolizumab over platinum-doublet chemotherapy. In Study 1624, the OS HR was 0.68 (95% CI, 0.53-0.87; P = 0.0022) favoring cemiplimab-rwlc over platinum-doublet chemotherapy. The progression-free survival (PFS) effect sizes for these anti-PD-L1 antibodies were also comparable across their respective registrational trials, and their safety profiles were consistent with the anti-PD-L1 class adverse event profile. The consistent survival benefits and manageable toxicity profiles of these single-agent anti-PD-L1 antibodies have established them as important treatment options in the PD-L1-high NSCLC treatment landscape. FDA approvals of these anti-PD-L1 antibodies, based on their favorable benefit-risk profiles, present effective chemotherapy-free therapeutic options for patients with advanced PD-L1-high NSCLC in the United States.

Functional status predicts major complications and death after endovascular repair of abdominal aortic aneurysms.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is considered a lower risk option for treating abdominal aortic aneurysms and is of particular utility in patients with poor functional status who may be poor candidates for open repair. However, the specific contribution of preoperative functional status to EVAR outcomes remains poorly defined. We hypothesized that impaired functional status, based simply on the ability of patients to perform activities of daily living, is associated with worse outcomes after EVAR. METHODS: Patients undergoing nonemergent EVAR for abdominal aortic aneurysm between 2010 and 2014 were identified in the National Surgical Quality Improvement Program (NSQIP) database. The primary outcomes were 30-day mortality and major operative and systemic complications. Secondary outcomes were inpatient length of stay, need for reoperation, and discharge disposition. Using the NSQIP-defined preoperative functional status, patients were stratified as independent or dependent (either partial or totally dependent) and compared by univariate and multivariable analyses. RESULTS: Of 13,432 patients undergoing EVAR between 2010 and 2014, 13,043 were independent (97%) and 389 were dependent (3%) before surgery. Dependent patients were older and more frequently minorities; had higher rates of chronic pulmonary, heart, and kidney disease; and were more likely to have an American Society of Anesthesiologists score of 4 or 5. On multivariable analysis, preoperative dependent status was an independent risk factor for operative complications (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.5-3.9), systemic complications (OR, 2.8; 95% CI, 2.0-3.9), and 30-day mortality (OR, 3.4; 95% CI, 2.1-5.6). Secondary outcomes were worse among dependent patients. CONCLUSIONS: Although EVAR is a minimally invasive procedure with substantially less physiologic stress than in open aortic repair, preoperative functional status is a critical determinant of adverse outcomes after EVAR in spite of the minimally invasive nature of the procedure. Functional status, as measured by performance of activities of daily living, can be used as a valuable marker of increased perioperative risk and may identify patients who may benefit from preoperative conditioning and specialized perioperative care.

Is a mandatory intensive care unit stay needed after liver transplantation? Feasibility of fast-tracking to the surgical ward after liver transplantation.

The continuation of hemodynamic, respiratory, and metabolic support for a variable period after liver transplantation (LT) in the intensive care unit (ICU) is considered routine by many transplant programs. However, some LT recipients may be liberated from mechanical ventilation shortly after the discontinuation of anesthesia. These patients might be appropriately discharged from the postanesthesia care unit (PACU) to the surgical ward and bypass the ICU entirely. In 2002, our program started a fast-tracking program: select LT recipients are transferred from the operating room to the PACU for recovery and tracheal extubation with a subsequent transfer to the ward, and the ICU stay is completely eliminated. Between January 1, 2003 and December 31, 2007, 1045 patients underwent LT at our transplant program; 175 patients were excluded from the study. Five hundred twenty-three of the remaining 870 patients (60.10%) were fast-tracked to the surgical ward, and 347 (39.90%) were admitted to the ICU after LT. The failure rate after fast-tracking to the surgical ward was 1.90%. The groups were significantly different with respect to the recipient age, the raw Model for End-Stage Liver Disease (MELD) score at the time of LT, the recipient body mass index (BMI), the retransplantation status, the operative time, the warm ischemia time, and the intraoperative transfusion requirements. A multivariate logistic regression analysis revealed that the raw MELD score at the time of LT, the operative time, the intraoperative transfusion requirements, the recipient age, the recipient BMI, and the absence of hepatocellular cancer/cholangiocarcinoma were significant predictors of ICU admission. In conclusion, we are reporting the largest single-center experience demonstrating the feasibility of bypassing an ICU stay after LT.

Should donation after cardiac death liver grafts be used for retransplantation?

INTRODUCTION: Donation after cardiac death (DCD) donors provide an important source of livers that has been used to expand the donor pool. As a consequence of increased numbers of OLT, allograft failure due to early and late complications and disease recurrence are more commonly encountered. The only life saving treatment for patients with liver allograft failure is liver re-transplantation (LR). The use of DCD liver grafts for LR is controversial. MATERIAL AND METHODS: Between February 1998 and June 2008, 10 patients underwent LR with DCD allografts. Five (50%) patients had no post operative complications. The 30 day, 1 year, and 3 year patient survival are 80, 60, and 60%, respectively. When DCD grafts are used for sick patients with high MELD scores for LR, the patient and graft survivals are prohibitively low. CONCLUSION: We do not recommend utilization of DCD liver grafts for LR if a candidate recipient has moderate to high MELD score.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus.

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV(+) patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV(+) patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV(+) recipients. Seventy-seven HCV(+) patients who received DCD liver grafts were compared to 77 matched HCV(+) patients who received donation after brain death (DBD) liver grafts and 77 unmatched non-HCV patients who received DCD liver grafts. There were no differences in 1-, 3-, and 5-year patient or graft survival among the groups. Multivariate analysis showed that the Model for End-Stage Liver Disease score [hazard ratio (HR) = 1.037, 95% confidence interval (CI) = 1.006-1.069, P = 0.018] and posttransplant cytomegalovirus infection (HR = 3.367, 95% CI = 1.493-7.593, P = 0.003) were significant factors for graft loss. A comparison of the HCV(+) groups for fibrosis progression based on protocol biopsy samples up to 5 years post-transplant did not show any difference; in multivariate analysis, HCV genotype 1 was the only factor that affected progression to stage 2 fibrosis (genotype 1 versus non-1 genotypes: HR = 2.739, 95% CI = 1.047-7.143, P = 0.040). In conclusion, this match-controlled, retrospective analysis demonstrates that DCD liver graft utilization does not cause untoward effects on disease progression or patient and graft survival in comparison with DBD liver grafts in HCV(+) patients.