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Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience. We retrospectively reviewed all patients with HR + HER2- ABC treated with a palbociclib-based therapy as first or second line for ABC, with an initial prescription from November 2016 to December 2018. Clinical, laboratory and imaging data were retrieved from electronic records. Data lock was December 31st, 2019. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. We included 310 consecutive patients. Median age was 61.8 years old. Palbociclib was prescribed in first line in 225 patients (72.6%). Before palbociclib-based therapy initiation, 122 patients (39.3%) were endocrine naive, 96 (31.0%) endocrine sensitive and 92 (29.7%) endocrine resistant. Median follow-up was 20.7 months. Median progression free survival (PFS) was 23.4 months (95%CI: 21.6-NR) in endocrine naive patients, 22.7 months (95%CI: 14.7-NR) in endocrine sensitive, and 13.4 months (95%CI: 10.7–20.8) in endocrine resistant. At 12 months from the initiation of palbociclib, 94.5% of patients were alive. By multivariate analysis, poor prognosis factors for PFS were identified in the endocrine naive/sensitive population: initial ECOG status 2, previous endocrine therapy for ABC, 3 metastatic sites or more. Toxicity profile was similar to previously published data. In a non-selected population of patients with HR + HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported. • Efficacy of palbociclib in advanced breast cancer in real-life is very close to that from the pivotal trials. • Long-term follow-up of patients treated with palbociclib show no cumulative adverse events. [ABSTRACT FROM AUTHOR]

Approximately 40% of pts with HR+, HER2– ABC have mutations (mut) in PIK3CA, which encodes α-PI3K and leads to PI3K pathway hyperactivation and potentially ET resistance. ALP is a selective inhibitor of α-PI3K that, in combination with fulvestrant (FUL), significantly improved median progression-free survival (PFS) vs placebo + FUL in pts with PIK3CA-mut, HR+ HER2– ABC in the phase 3 SOLAR-1 trial (11.0 vs 5.7 mo, respectively; HR 0.65; 95% CI, 0.50-0.85; P < 0.001). BYLieve is an ongoing phase 2, multicenter, open-label, noncomparative study assessing ALP + ET (FUL or letrozole [LET]) in pts with PIK3CA-mut HR+, HER2– ABC who progressed on/after prior treatments (tx). BYLieve includes women (any menopausal status) and men with PIK3CA-mut, HR+, HER2– ABC and evidence of tumor progression on prior tx. Cohorts A and B comprise pts who received a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET as their last tx. With the adoption of Amendment 3, a new cohort (C) enrolls pts who had systemic chemotherapy or ET as last prior tx and who failed aromatase inhibitor (AI) in the adjuvant or metastatic setting. In the advanced setting, ≤2 anticancer tx (including ≤1 chemotherapy) are allowed. Pts must have ≥1 measurable lesion per RECIST criteria or ≥ 1 predominantly lytic bone lesion. Key exclusion criteria include prior PI3Ki tx and type 1 or uncontrolled type 2 diabetes. Study tx comprises: Cohort A (prior CDK 4/6i + AI), ALP 300 mg once daily (qd) + FUL 500 mg Q28d + C1d15; Cohort B (prior CDK 4/6i + FUL), ALP 300 mg qd + LET 2.5 mg qd; Cohort C, ALP 300 mg qd + FUL 500 mg Q28d + C1d15. The primary endpoint is the proportion of pts free of progression at 6 mo per local investigator assessment for each cohort. Secondary endpoints include PFS, PFS2, ORR, and CBR. Safety and tolerability will also be assessed, including fasted or random blood glucose levels (non-fasted). Tumor tissue and circulating tumor DNA are collected for biomarker assessments. The study is ongoing and currently recruiting pts, with increase in planned overall enrollment from 160 to 340 pts. NCT03056755. Medical editorial assistance was provided by Joe Hodgson of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation. Novartis Pharmaceuticals Corporation. Novartis Pharmaceuticals Corporation. E. Ciruelos: Advisory / Consultancy, Speaker and consultant fee: Novartis, Roche, Pfzier, Lilly. T. Bachelot: Research grant / Funding (self), Research grant: Novartis; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Pfzier. S. Chia: Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Pfzier. D. Juric: Advisory / Consultancy, Scientific Advisory Board: Novartis, Genentech, Eisai, Ipsen, EMD Serono. N. Turner: Advisory / Consultancy: AstraZeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche/Genentech, Tesaro, Bicycle Therapeutics; Research grant / Funding (self): AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Guardant Health. A. Ridolfi: Full / Part-time employment: Novartis. N. Sophos: Full / Part-time employment: Novartis. B. Cooper: Full / Part-time employment: Novartis. A. Thuerigen: Full / Part-time employment: Novartis. H.S. Rugo: Research grant / Funding (institution): Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics and Macrogenics; Travel / Accommodation / Expenses: Lilly, Mylan, Pfizer, Amgen, Merck and Puma. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant hormone therapy (HT) promotes breast-conserving surgery (BCS) and minimizes treatment-related toxicities for oestrogen receptor (ER)-positive HER2 negative breast cancer (BC). We aimed to evaluate the response rates to an AI (anastrozole) or an antioestrogen (fulvestrant) and to identify specific biomarkers of sensitivity to both treatments. Patients and Methods: A phase II multicentre, open-label trial was conducted to evaluate the efficacy of anastrozole and fulvestrant. 116 postmenopausal patients (pts) with ER positive, HER2 negative, operable BC were recruited in 6 centers and randomly assigned to receive either neoadjuvant anastrozole (arm A; 1mg/day) or fulvestrant (arm B; 500mg, with a loading dose during first month then q4w) for 4 months (mo). Pts with a good clinical response estimated by the clinician at 4 mo were allowed to pursue treatment for 2 more mo (i.e. up to 6 mo). The primary endpoint was to evaluate the best clinical response (by palpation) by RECIST criteria at 6 mo (or 4 mo). US and MR imaging were performed at baseline, after 1 mo treatment, and before surgery. Pathological response was evaluated using Sataloff classification. Follow-up is planned for 5 yrs. Results: Between Oct 2007 and Apr 2011, 59 pts were randomized to arm A and 57 to arm B. Main baseline characteristics were well-balanced between the 2 arms: Median age was 68 yrs- old (53-91) in arm A and 74 yrs-old (51-88) in arm B. Histological grades were EE I-II in 53 pts (89 %) and 49 pts (86%) and median clinical size before treatment was 41.5 mm and 42.3 mm in arm A and B respectively. Neither SAE nor grade 3/4 toxicity was reported. The most common treatment-related AEs were grade1/2 hot flushes (27% and 12% of pts in arm A and B respectively), and musculoskeletal symptoms (20% and 21%). 35 pts in arm A and 29 pts in arm B continued assigned treatment up to 6 mo depending on the clinical response evaluated at 4 mo. Also, the clinical response rate was estimated at 4 mo orat 6 mo. 1 death post-surgery was reported in arm B with no proven relationship with treatment. Overall clinical response rates (CR + PR) at 4 or 6 mo were 62% (CI 95% [49-75]) in arm A and 46% (CI 95% [32-59]) in arm B. Clinical response rate amelioration at 6 mo was observed among 15% of pts in each arm. BCS was performed in 59% of pts in arm A and 49% in arm B. (1 pt from arm B refused surgery). Pathological response according to Sataloff classification: TA and TB tumor responses were observed in 17/59 pts (29%) in arm A vs 12/57 (21%) in arm B respectively. Conclusions: Both anastrozole and fulvestrant show excellent efficacy and tolerability as neoadjuvant therapy in post-menopausal pts with endocrine-dependent, HER2-negative BC. Objective response rates and improvement in surgical outcome seem to be more frequent with anastrozole. However disease stabilization and tolerability are in favour of fulvestrant. Our data suggest that neo-adjuvant HT improves surgical options for HR+ post-menopausal women. Correlation between clinical & pathological responses and outcome as well as the identification of markers of sensitivity to both treatments will be also studied. [ABSTRACT FROM AUTHOR]

Background In early breast cancer (BC), there has been a trend to escalate endocrine therapy (ET) and to de-escalate chemotherapy (CT). However, the impact of ET versus CT on the quality of life (QoL) of early BC patients is unknown. Here, we characterize the independent contribution of ET and CT on patient-reported outcomes (PROs) at 2 years after diagnosis. Patients and methods We prospectively collected PROs in 4262 eligible patients using the European Organization for Research and Treatment of Cancer QLQ-C30/BR23 questionnaires inside CANTO trial (NCT01993498). The primary outcome was the C30 summary score (C30-SumSc) at 2 years after diagnosis. Results From eligible patients, 37.2% were premenopausal and 62.8% postmenopausal; 81.9% received ET and 52.8% CT. In the overall cohort, QoL worsened by 2 years after diagnosis in multiple functions and symptoms; exceptions included emotional function and future perspective, which improved over time. ET (P int = 0.004), but not CT (P int = 0.924), had a persistent negative impact on the C30-SumSc. In addition, ET negatively impacted role and social function, pain, insomnia, systemic therapy side-effects, breast symptoms and further limited emotional function and future perspective recovery. Although CT had no impact on the C30-SumSc at 2-years it was associated with deteriorated physical and cognitive function, dyspnea, financial difficulties, body image and breast symptoms. We found a differential effect of treatment by menopausal status; in premenopausal patients, CT, despite only a non-significant trend for deteriorated C30-SumSc (P int = 0.100), was more frequently associated with QoL domains deterioration than ET, whereas in postmenopausal patients, ET was more frequently associated with QoL deterioration, namely using the C30-SumSc (P int = 0.004). Conclusion(s) QoL deterioration persisted at 2 years after diagnosis with different trajectories by treatment received. ET, but not CT, had a major detrimental impact on C30-SumSc, especially in postmenopausal women. These findings highlight the need to properly select patients for adjuvant ET escalation. [ABSTRACT FROM AUTHOR]