plus fulvestrant (n = 284) or placebo plus fulvestrant (n = 287).
Fulvestrant 500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each28-day cycle during treatment phase.
Two patients (0.7%) died while on treatment with PIQRAY plus fulvestrant due to causes other than theunderlying malignancy. Causes of death included one cardio-respiratory arrest and one second primarymalignancy. Neither was suspected to be related to study treatment.
Serious adverse reactions occurred in 35% of patients receiving PIQRAY plus fulvestrant. Serious adversereactions in > 2% of patients receiving PIQRAY plus fulvestrant included hyperglycemia (10%), rash (3.5%),diarrhea (2.8%), acute kidney injury (2.5%), abdominal pain (2.1%), and anemia (2.1%).
Osteonecrosis of the jaw (ONJ) was reported in 4.2% of patients (12/284) in the PIQRAY plus fulvestrant armcompared to 1.4% of patients (4/287) in the placebo arm. All patients experiencing ONJ had prior orconcomitant bisphosphonates or RANK-ligand inhibitor administration.
Among patients receiving PIQRAY plus fulvestrant, 4.6% permanently discontinued both PIQRAY andfulvestrant and 21% permanently discontinued PIQRAY alone, due to ARs. The most frequent ARs leading totreatment discontinuation of PIQRAY in > 2% patients receiving PIQRAY plus fulvestrant were hyperglycemia(6%), rash (4.2%), diarrhea (2.8%), and fatigue (2.5%).
Dose reductions due to ARs occurred in 55% of patients receiving PIQRAY plus fulvestrant. The most frequentARs leading to dose reduction in > 2% patients receiving PIQRAY plus fulvestrant were hyperglycemia (29%),rash (9%), diarrhea (6%), stomatitis (3.5%) and mucosal inflammation (2.1%).
The most common adverse reactions including laboratory abnormalities (all grades, incidence ≥ 20%) wereglucose increased, creatinine increased, diarrhea, rash, lymphocyte count decreased, GGT increased, nausea,ALT increased, fatigue, hemoglobin decreased, lipase increased, decreased appetite, stomatitis, vomiting,weight decreased, calcium decreased, glucose decreased, aPTT prolonged, and alopecia.
Adverse reactions and laboratory abnormalities are listed in Table 6 and Table 7, respectively.
Table 6: Adverse Reactions Occurring in ≥ 10% and ≥ 2% Higher than Placebo Arm in SOLAR-1
(All Grades)
PIQRAY plus fulvestrant
N = 284
Placebo plus fulvestrant
N = 287
Adverse reactions All Grades
%
Grade 3-4
%
All Grades
%
Grade 3-4
%
Gastrointestinal disorders
Diarrhea 58 7
* 16 0.3*
Nausea 45 2.5* 22 0.3*
Stomatitis1 30 2.5* 6 0
*
Vomiting 27 0.7* 10 0.3*
Abdominal pain2 17 1.4* 11 1
*
Dyspepsia 11 0
* 6 0
PIQRAY plus fulvestrant
N = 284
Placebo plus fulvestrant
N = 287
General disorders and administration site conditions
Fatigue3 42 5
* 29 1
*
Mucosal inflammation 19 2.1* 1 0
*Edema peripheral 15 0
* 5 0.3*
Pyrexia 14 0.7 4.9 0.3*
Mucosal dryness4 12 0.4* 4.2 0
*Infections and infestations
Urinary tract infection5 10 0.7* 5 1
*Investigations
Weight decreased 27 3.9* 2.1 0
*Metabolism and nutrition disorders
Decreased appetite 36 0.7* 10 0.3*
Nervous system disorders
Dysgeusia6 18 0.4* 3.5 0
*Headache 18 0.7* 13 0
*Skin and subcutaneous tissue disorders
Rash7 52 20* 7 0.3*
Alopecia 20 0
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