title: Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience.
abstract: OBJECTIVE
  This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability.
  
  
  METHODS
  163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C).
  
  
  RESULTS
  RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7-11) (A), 10 months (95% CI 9-11) (B), and 5 months (95% CI 2-8) (C), p = 0.956. OS was 38 months (95% CI 24-38) (A), median not reached (B), and 13 months (95% CI 10-25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3-4), asthenia 46.0% (6.1% grade 3-4), hypercholesterolemia 46.0% (0.6% grade 3-4), and hyperglycemia 35.6% (5.5% grade 3-4). The main reason for discontinuation/interruption was grade 2-3 stomatitis.
  
  
  CONCLUSIONS
  No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy.
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy. m.ciccarese@libero.it.
authors.forename: Mariangela
authors.identifier: http://orcid.org/0000-0002-0273-5209
authors.initials: M
authors.lastname: Ciccarese
authors.affiliation: Department of Medical Oncology, "Regina Elena" National Cancer Institute, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Department of Oncology/Haemathology, University Hospital, Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Moscetti
authors.affiliation: Oncology Department, "AO S. Gerardo", Monza, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Cazzaniga
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Petrucelli
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Rosachiara
authors.initials: R
authors.lastname: Forcignanò
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Laura Isabella
authors.initials: LI
authors.lastname: Lupo
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Matteis
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Vincenzo Emanuele
authors.initials: VE
authors.lastname: Chiuri
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cairo
authors.affiliation: Medical Oncology Unit, "Sacro Cuore di Gesù Fatebenefratelli" Hospital, Benevento, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Febbraro
authors.affiliation: Medical Oncology Unit, "Sacro Cuore di Gesù Fatebenefratelli" Hospital, Benevento, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Giordano
authors.affiliation: Medical Oncology Unit, "S. Carlo" Hospital, Potenza, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Giampaglia
authors.affiliation: Medical Oncology Unit, "S. Carlo" Hospital, Potenza, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Bilancia
authors.affiliation: Department of Oncology, "ASST Fatebenefratelli Sacco", Milan, Italy.
authors.forename: Nicla
authors.initials: N
authors.lastname: La Verde
authors.affiliation: Department of Medical Oncology, "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy.
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.affiliation: Department of Medical Oncology, "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, FG, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Morritti
authors.affiliation: Department of Medical Oncology, "Giovanni Paolo II" Institute, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giotta
authors.affiliation: Department of Medical Oncology, "Giovanni Paolo II" Institute, Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.affiliation: Department of Medical Oncology, "Giovanni Paolo II" Institute, Bari, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Latorre
authors.affiliation: Medical Oncology Unit, "S. Cuore di Gesù" Hospital, Gallipoli, LE, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Scavelli
authors.affiliation: Oncology Unit, "Ospedali Riuniti" Hospital, Foggia, Italy.
authors.forename: Sante
authors.initials: S
authors.lastname: Romito
authors.affiliation: Oncology Unit, "Di Venere" Hospital, Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cusmai
authors.affiliation: Oncology Unit, "Di Venere" Hospital, Bari, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Palmiotti
authors.affiliation: Medical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
authors.forename: Giammarco
authors.initials: G
authors.lastname: Surico
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D000068338:Everolimus / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D013280:Stomatitis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology
chemical_list: D000730:Androstadienes; D000068338:Everolimus; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human; C056516:exemestane
keywords: Breast cancer; Dose intensity; Everolimus; Real-world population; Side effects