title: Palbociclib and Letrozole in Advanced Breast Cancer.
abstract: A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication.
  
  
  
  In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety.
  
  
  
  The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group.
  
  
  
  Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib-letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427 .).
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Stephen
authors.initials: S
authors.lastname: Jones
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Lipatov
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Janice M
authors.initials: JM
authors.lastname: Walshe
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Stacy
authors.initials: S
authors.lastname: Moulder
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Eric
authors.initials: E
authors.lastname: Gauthier
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Dongrui R
authors.initials: DR
authors.lastname: Lu
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Sophia
authors.initials: S
authors.lastname: Randolph
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.affiliation: From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D017698:Postmenopause; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011960:Receptors, Estrogen / Q000032:analysis; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011960:Receptors, Estrogen; D014230:Triazoles; D000077289:Letrozole; D018844:Cyclin-Dependent Kinases; C500026:palbociclib