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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., Competing Interests: Erica L. MayerConsulting or Advisory Role: Lilly, Novartis, AstraZeneca, Gilead SciencesResearch Funding: Pfizer (Inst) Christian FeslResearch Funding: Pfizer (Inst) Dominik HlauschekResearch Funding: Pfizer (Inst) Laura Garcia-EstevezConsulting or Advisory Role: Daiichi Sankyo/Astra Zeneca, Palex, Seattle GeneticsResearch Funding: Roche/Genentech (Inst) Nicholas ZdenkowskiHonoraria: Roche, Pfizer, EisaiConsulting or Advisory Role: Lilly, AstraZeneca, EisaiResearch Funding: Roche (Inst), Pfizer (Inst)Travel, Accommodations, Expenses: Roche, Amgen, Novartis Kathy D. MillerThis author is the Senior Deputy Editor of Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Merck, Genentech/Roche, Athenex, AstraZeneca, Bristol Myers Squibb/CelgeneResearch Funding: Taiho Pharmaceutical (Inst), Novartis (Inst), Seattle Genetics (Inst), Pfizer (Inst), Astex Pharmaceuticals (Inst), British Biotech (Inst), CytomX Therapeutics (Inst), Alphamab (Inst) Marija BalicConsulting or Advisory Role: Amgen, AstraZeneca, Daiichi Sankyo/Astra Zeneca, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, SamsungSpeakers' Bureau: Amgen, AstraZeneca, Daiichi Sankyo/Astra Zeneca, Lilly, Novartis, Pierre Fabre, Pfizer, Roche, Seattle GeneticsResearch Funding: Lilly (Inst), Novartis (Inst), Pfizer (Inst)Travel, Accommodations, Expenses: MSD Ingrid A. MayerConsulting or Advisory Role: Novartis, AstraZeneca, Lilly, Genentech, GlaxoSmithKline, Immunomedics, Macrogenics, Pfizer, AbbVie, Seattle Genetics, Puma Biotechnology, Cyclacel, Blueprint Medicines, SanofiResearch Funding: Novartis (Inst), Pfizer (Inst), Genentech (Inst) David CameronConsulting or Advisory Role: Lilly (Inst), Novartis (Inst), Novartis (Inst), Research Triangle Institute RTI Health Solutions (Inst), Daiichi Sankyo (Inst), Prima BioMed (Inst), Merck Sharp & Dohme (Inst), Zymeworks (Inst), Eisai (Inst), Puma Biotechnology (Inst), Pfizer (Inst), Oncolytics (Inst), Roche (Inst), Roche (Inst), Samsung Bioepis (Inst), Seattle Genetics (Inst), Synthon (Inst), Clarity Pharmaceuticals (Inst), Bexon/Zymeworks (Inst), Sanofi (Inst)Research Funding: Roche (Inst), Novartis (Inst), AstraZeneca (Inst) Eric P. WinerHonoraria: Genentech/Roche, Genomic HealthConsulting or Advisory Role: Leap Therapeutics, Seattle Genetics, Jounce Therapeutics, GlaxoSmithKline, Carrick Therapeutics, Lilly, G1 Therapeutics, Syros Pharmaceuticals, Genentech/Roche, Gilead Sciences, Zymeworks, AthenexResearch Funding: Genentech (Inst)Other Relationship: InfiniteMD José Juan Ponce LorenzoHonoraria: Seattle Genetics, Novartis, Pfizer, AstraZeneca/Daiichi Sankyo, Lilly, RocheConsulting or Advisory Role: Seattle Genetics, Novartis, AstraZeneca/Daiichi Sankyo, Roche Tufia C. HaddadResearch Funding: Takeda (Inst) Hiroji IwataHonoraria: Chugai Pharma, AstraZeneca, Eisai, Pfizer, Daiichi Sankyo, Lilly Japan, Kyowa Hakko Kirin, Taiho PharmaceuticalConsulting or Advisory Role: Chugai Pharma, Daiichi Sankyo, Pfizer, AstraZeneca, Lilly Japan, Kyowa Hakko Kirin, NovartisResearch Funding: MSD (Inst), AstraZeneca (Inst), Kyowa Hakko Kirin (Inst), Daiichi Sankyo (Inst), Chugai Pharma (Inst), Nihonkayaku (Inst), Lilly Japan (Inst), Novartis (Inst), Bayer (Inst), Pfizer (Inst), Boehringer Ingelheim (Inst), Sanofi (Inst) Matthew GoetzConsulting or Advisory Role: Lilly, bioTheranostics, Genomic Health, Novartis, Eisai, Sermonix Pharmaceuticals, Context Therapeutics, Pfizer, BiovicaResearch Funding: Lilly (Inst), Pfizer (Inst), Sermonix Pharmaceuticals (Inst)Patents, Royalties, Other Intellectual Property: Methods and Materials for Assessing Chemotherapy Responsiveness and Treating Cancer, Methods and Materials for Using Butyrylcholinesterases to Treat Cancer, Development of Human Tumor Xenografts from Women with Breast Cancer Treated with Neoadjuvant Chemotherapy (Inst)Travel, Accommodations, Expenses: Lilly Fatima CardosoConsulting or Advisory Role: Roche, Novartis, Pfizer, AstraZeneca, Teva, Astellas Pharma, Merus, Celgene, Eisai, Daiichi Sankyo, Genentech, Merck Sharp & Dohme, Sanofi, Pierre Fabre, Macrogenics, Amgen, GE Healthcare, GlaxoSmithKline, Mylan, Mundipharma, Seattle Genetics, Samsung Bioepis, Medscape, Prime OncologyTravel, Accommodations, Expenses: Pfizer, Roche, AstraZeneca Tiffany A. TrainaConsulting or Advisory Role: Genentech/Roche, Pfizer, AstraZeneca, Merck, Puma Biotechnology, Athenex, Daiichi Sankyo, Ionis Pharmaceuticals, Seattle Genetics, Eisai, Exact Sciences, Foundation Medicine, Ayala Pharmaceuticals, Gilead Sciences, Blueprint Medicines, Ellipses Pharma, Fuji Pharma, ITeos Therapeutics, AgendiaResearch Funding: Eisai (Inst), Pfizer (Inst), Novartis (Inst), Innocrin Pharma (Inst), AstraZeneca (Inst), Astellas Pharma (Inst), Immunomedics (Inst), Genentech/Roche (Inst), Daiichi Sankyo (Inst), Carrick Pharm (Inst), Ayala Pharmaceuticals (Inst) Urs BreitensteinConsulting or Advisory Role: AstraZeneca (Inst), Elie Lilly (Inst), Novartis (Inst), Pierre Fabre (Inst), Roche (Inst) Kerstin AckerlResearch Funding: Pfizer (Inst) Otto Metzger FilhoHonoraria: Grupo Oncoclinicas, RocheResearch Funding: Susan G. Komen for the Cure (Inst), Pfizer (Inst), Roche/Genentech (Inst), Eisai (Inst), Cascadian Therapeutics (Inst), AbbVie (Inst)Travel, Accommodations, Expenses: Grupo Oncoclinicas Karin ZehetnerResearch Funding: Pfizer (Inst) Kadine SolomonEmployment: Alliance Foundation TrialsStock and Other Ownership Interests: Pfizer, Merck, Moderna Therapeutics Sarra El-AbedEmployment: Astellas Pharma (I), argenx (I)Research Funding: Novartis (Inst), Roche/Genentech (Inst), Pfizer (Inst) Kathy Puyana TheallEmployment: Pfizer (I)Stock and Other Ownership Interests: Pfizer (I)Honoraria: PfizerTravel, Accommodations, Expenses: Pfizer Dongrui Ray LuEmployment: PfizerStock and Other Ownership Interests: Pfizer Amylou DueckPatents, Royalties, Other Intellectual Property: Royalties from licensing fees for a patient symptom questionnaire (MPN-SAF) Michael GnantEmployment: Sandoz (I)Honoraria: Amgen, Novartis, AstraZeneca, LillyConsulting or Advisory Role: Daiichi-Sankyo, Veracyte, Tolmar, LifeBrain, Lilly Angela DeMicheleResearch Funding: Pfizer (Inst), Genentech (Inst), Calithera Biosciences (Inst), Novartis (Inst)No other potential conflicts of interest were reported.

In this study we tried to find out if fear can be detected from human body odours. Female subjects wore under-arm axillary pads while watching a terrifying film. Saliva cortisol samples were taken before and after the film presentation as a hormonal measure for the fear response. The fear experience itself was measured by Spielberger's State-Trait Anxiety Inventory. A "neutral" film, shown one day after the "fear" film, was used as a control in a repeated measures design. In part two of the experiment, the axillary pads were presented to female subjects in a triple forced choice test. Results show that subjects were able to discriminate between fear and non-fear axillary pads, suggesting that women are indeed able to detect "the scent of fear". A direct correlation between induced fear, changes in cortisol levels and smell ratings could not be established. Thus cortisol levels are probably not the inducer of the scent of fear and a hypothetical fear pheromone could have other origins.