Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas.

BACKGROUND: To date, single-agent immune checkpoint inhibitor (CPI) therapy has proven to be ineffective against biomarker-unselected extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). The efficacy of CPI in combination with chemotherapy remains under investigation. METHODS: Patients with advanced, progressive EP-PDNECs were enrolled in a two-part study of pembrolizumab-based therapy. In Part A, patients received pembrolizumab alone. In Part B, patients received pembrolizumab plus chemotherapy. PRIMARY ENDPOINT: objective response rate (ORR). Secondary endpoints: safety, progression-free survival (PFS) and overall survival (OS). Tumours were profiled for programmed death-ligand 1 expression, microsatellite-high/mismatch repair deficient status, mutational burden (TMB), genomic correlates. Tumour growth rate was evaluated. RESULTS: Part A (N = 14): ORR (pembrolizumab alone) 7% (95% CI, 0.2-33.9%), median PFS 1.8 months (95% CI, 1.7-21.4), median OS 7.8 months (95% CI, 3.1-not reached); 14% of patients (N = 2) had grade 3/4 treatment-related adverse events (TRAEs). Part B (N = 22): ORR (pembrolizumab plus chemotherapy) 5% (95% CI, 0-22.8%), median PFS 2.0 months (95% CI, 1.9-3.4), median OS 4.8 months (95% CI, 4.1-8.2); 45% of patients (N = 10) had grade 3/4 TRAEs. The two patients with objective response had high-TMB tumours. DISCUSSION: Treatment with pembrolizumab alone and pembrolizumab plus chemotherapy was ineffective in advanced, progressive EP-PDNECs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03136055.

Parental Leave: What Do Physician Societies Provide for Their Employees?

Introduction: Parental leave yields significant health benefits for parents and children. While many medical associations endorse parental leave, it is unknown what parental leave they provide for their employees. Objective: To assess parental leave policies of national physician societies for their employees including paid versus unpaid and parity between birth mothers and non-birthing parents. Methods and Materials: A cross-sectional analysis in 2023 examined parental leave policies of national physician societies, including the American Medical Association (AMA), American Osteopathic Association (AOA), and six specialty societies: American College of Obstetricians and Gynecologists (ACOG), American College of Osteopathic Obstetricians and Gynecologists (ACOOG), American Academy of Pediatrics (AAP), American College of Osteopathic Pediatricians (ACOP), American Academy of Family Physicians (AAFP), and American College of Osteopathic Family Physicians (ACOFP). Examination of policies included: duration, whether paid or unpaid; qualifications before receiving benefit; and whether non-birthing, adoptive, and foster parents were covered. Results: Among the eight societies surveyed, two (25%) did not disclose their policies (ACOG, ACOP), and one (12.5%) lacked a policy (ACOOG). Of the remaining five, two (40%) offered paid leave (AMA, AAP), while three (60%) provided unpaid leave in line with legal requirements (AOA, AAFP, ACOFP). Benefits for non-birthing parents mirrored those for birth mothers, although the AMA offered birth mothers enhanced benefits. Conclusions: Only a minority of surveyed physician societies provide paid parental leave. Physician societies should consider providing paid parental leave for their employees and making their policies publicly available to promote and model the benefit of paid parental leave.