Abstract P3-12-10: First 6-month report of the longitudinal PHACS study (<u>P</u>harmacology and <u>H</u>ormonotherapy (HT) for <u>A</u>djuvant breast <u>C</u>ancer (BC) <u>S</u>tudy, NCT01127295)
Authors: H Roché, L Venat-Bouvet, M Debled, W Jacot, E Suc, F Dalenc, D Molnar-Stanciu, N Dohollou, D Franck, C Ferrer, H Laharie-Mineur, S Lavau-Denes, C Massabeau, V Mauries, J Robert, F Pinguet, P Marquet, A Evrard, E Chatelut, T Filleron
Journal: Cancer Research (2018)

Abstract Background: BC is a hormone-dependent disease for 75% of pts. HT is used in both adjuvant and metastatic settings for hormone–receptor (HR) positive tumors. In adjuvant situation, a 5-year HT period at least is recommended. Side-effects (SE) frequently alter quality of life and compliance, reducing the well-known benefits in risks of relapses and specific deaths. Underlying mechanisms are well understood for estrogen deprivation-induced events such as hot flashes, but little is known on arthralgia under aromatase inhibitors (AI). So, pharmacogenomics (PG), pharmacokinetics (PK), potential medications interactions are of value to explain individual drugs exposures, possible related side-effects and compliance to treatment. Methods: We performed a prospective, multicenter, longitudinal study registering early clinical outcomes and SE during the first 3 years of adjuvant HT with tamoxifen (T) or AI. All tumors expressed at least one HR (&amp;gt;10%). The choice of HT molecule and one-drug or sequential treatment were left to the investigator. Pts were followed every 6 months with clinical examination by the referent oncologist and PK sampling each time. Biologic research consisted in PG investigations of different genes involved in the PK and pharmacodynamics of T and AI (95 SNPs) at baseline. SE, concurrent medications and compliance were registered by both the pts on a diary card and the physician. Evaluation was done only on new occurrence or increased grade of symptoms. Results: This first report focuses on characteristics of the population and the results after the 6 first months of treatment. Between June 2010 and October 2014, 23 centers recruited 2000 pts. 23 were excluded leaving 1977 fully evaluable women; 879 (44%) started with T, 1098 (55%) with AI (554 letrozole (L), 390 anastrozole (A), 154 exemestane (E)). 56% of them had previously received chemotherapy, 96% radiotherapy and 8% trastuzumab. Main characteristics were well balanced between the 2 classes of drugs; T was given mainly for pre- or perimenopausal pts. Most frequent co-morbidities were hypertension (8% T, 31% AI) and dyslipidemia or diabetes (T 11%, AI 26%). To note, almost 30% of pts described arthralgias at entrance and 37% had hot flashes. At 6 months, 122 pts (6%; 43 T, 79 AI) had stopped treatment mainly for toxicity (11 T; 12 AI), progression or death (7 T; 4 IA), personal reasons (15 T; 37AI); 4 asked for changing T and 52 AI (equally for the 3 drugs). All these events were significantly more frequent for AI pts (p=0.042) and with E within the AI class (p&amp;lt;0.001). Main changes in onset or increased intensity of symptoms concerned hot flushes with all drugs (30%), asthenia (20%), insomnia (20%), weight gain (17%), arthralgias (15% for T, 30% for AI), thrombotic events (24 of which 11 with T). 3 grade3 SAE HT-related were reported. Biological data are reported in 2 other abst. (M. White-Koning. abst.#850248, F. Thomas, abst.#851525). Conclusions: These preliminary data on the first 6-months exposure to HT on adjuvant setting in the real-life confirm early rates of withdraws and toxicities. Longer follow-up and subsequent PK analysis should help to understand persistent side-effects and reasons for non-compliance to adjuvant HT. Citation Format: Roché H, Venat-Bouvet L, Debled M, Jacot W, Suc E, Dalenc F, Molnar-Stanciu D, Dohollou N, Franck D, Ferrer C, Laharie-Mineur H, Lavau-Denes S, Massabeau C, Mauries V, Robert J, Pinguet F, Marquet P, Evrard A, Chatelut E, Filleron T. First 6-month report of the longitudinal PHACS study (Pharmacology and Hormonotherapy (HT) for Adjuvant breast Cancer (BC) Study, NCT01127295) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-10.