Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03).

PURPOSE: The PALLAS study investigated whether the addition of palbociclib, an oral CDK4/6 inhibitor, to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In this analysis, we evaluated palbociclib exposure and discontinuation in PALLAS. METHODS: Patients with stage II-III HR+, HER2- disease were randomly assigned to 2 years of palbociclib with adjuvant ET versus ET alone. The primary objective was to compare iDFS between arms. Continuous monitoring of toxicity, dose modifications, and early discontinuation was performed. Association of baseline covariates with time to palbociclib reduction and discontinuation was analyzed with multivariable competing risk models. Landmark and inverse probability weighted per-protocol analyses were performed to assess the impact of drug persistence and exposure on iDFS. RESULTS: Of the 5,743 patient analysis population (2,840 initiating palbociclib), 1,199 (42.2%) stopped palbociclib before 2 years, the majority (772, 27.2%) for adverse effects, most commonly neutropenia and fatigue. Discontinuation of ET did not differ between arms. Discontinuations for non-protocol-defined reasons were greater in the first 3 months of palbociclib, and in the first calendar year of accrual, and declined over time. No significant relationship was seen between longer palbociclib duration or ≥ 70% exposure intensity and improved iDFS. In the weighted per-protocol analysis, no improvement in iDFS was observed in patients receiving palbociclib versus not (hazard ratio 0.89; 95% CI, 0.72 to 1.11). CONCLUSION: Despite observed rates of discontinuation in PALLAS, analyses suggest that the lack of significant iDFS difference between arms was not directly related to inadequate palbociclib exposure. However, the discontinuation rate illustrates the challenge of introducing novel adjuvant treatments, and the need for interventions to improve persistence with oral cancer therapies.

Efficacy and side effects of five sampling methods for soil earthworms (Annelida, Lumbricidae).

In this study, carried out on an experimental meadow in Austria, in non calceric cambisol, five common methods for sampling earthworms were jointly compared for their efficacy (handsorting, formalin, and allyl isothiocyanate (AITC) application, heat extraction in Kempson apparatus, and electrical octet method). Additionally, short- and long-term effects of the non-destructive of these methods (formalin and AITC application, octet method) on soil organisms (microarthropod abundance, phospholipid fatty acids) and shoot and root biomass were analysed. The Kempson extraction yielded the greatest number of individuals, followed by the octet method and handsorting. Formalin and AITC showed lower efficacy, but expelled high numbers of adult earthworms. Whereas AITC scarcely had nontarget effects on soil organisms, formalin negatively affected soil microorganisms and vegetation on the treated plots. The octet method seems to be well applicable especially in protected areas, since it is efficient, non-destructive and does not adversely affect soil organisms. The recommendations for method application are given, depending strongly on the scope of studies, as well as on ecological conditions and legal study site limitations.