Patients with HR-positive, HER2-negative advanced or metastatic breast cancer who have had disease progression on or after prior adjuvant or metastatic endocrine therapy
The safety of IBRANCE (125 mg/day) plus fulvestrant (500 mg) versus placebo plus fulvestrant was evaluated in PALOMA-3. The data described below reflect exposure to IBRANCE in 345 out of 517 patients with HR-positive, HER2-negative advanced or metastatic breast cancer who received at least 1 dose of IBRANCE plus fulvestrant in PALOMA-3. The median duration of treatment for IBRANCE plus fulvestrant was 10.8 months while the median duration of treatment for placebo plus fulvestrant arm was 4.8 months.
Dose reductions due to an adverse reaction of any grade occurred in 36% of patients receiving IBRANCE plus fulvestrant. No dose reduction was allowed for fulvestrant in PALOMA-3.
Permanent discontinuation associated with an adverse reaction occurred in 19 of 345 (6%) patients receiving IBRANCE plus fulvestrant, and in 6 of 172 (3%) patients receiving placebo plus fulvestrant. Adverse reactions leading to discontinuation for those patients receiving IBRANCE plus fulvestrant included fatigue (0.6%), infections (0.6%), and thrombocytopenia (0.6%).
The most common adverse reactions (≥10%) of any grade reported in patients in the IBRANCE plus fulvestrant arm by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia.
The most frequently reported Grade ≥3 adverse reactions (≥5%) in patients receiving IBRANCE plus fulvestrant in descending frequency were neutropenia and leukopenia.
Adverse reactions (≥10%) reported in patients who received IBRANCE plus fulvestrant or placebo plus fulvestrant in PALOMA-3 are listed in Table 6.
Table 6. Adverse Reactions (≥10%) in PALOMA-3Adverse Reaction | IBRANCE plus Fulvestrant (N=345) | Placebo plus Fulvestrant (N=172) |
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All Grades | Grade 3 | Grade 4 | All Grades | Grade 3 | Grade 4 |
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% | % | % | % | % | % |
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Grading according to CTCAE 4.0. CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients; N/A=not applicable. |
|
Infections and infestations |
Infections* | 47† | 3 | 1 | 31 | 3 | 0 |
Blood and lymphatic system disorders |
Neutropenia | 83 | 55 | 11 | 4 | 1 | 0 |
Leukopenia | 53 | 30 | 1 | 5 | 1 | 1 |
Anemia | 30 | 4 | 0 | 13 | 2 | 0 |
Thrombocytopenia | 23 | 2 | 1 | 0 | 0 | 0 |
Metabolism and nutrition disorders |
Decreased appetite | 16 | 1 | 0 | 8 | 1 | 0 |
Gastrointestinal disorders |
Nausea | 34 | 0 | 0 | 28 | 1 | 0 |
Stomatitis‡ | 28 | 1 | 0 | 13 | 0 | 0 |
Diarrhea | 24 | 0 | 0 | 19 | 1 | 0 |
Vomiting | 19 | 1 | 0 | 15 | 1 | 0 |
Skin and subcutaneous tissue disorders |
Alopecia | 18§ | N/A | N/A | 6¶ | N/A | N/A |
Rash# | 17 | 1 | 0 | 6 | 0 | 0 |
General disorders and administration site conditions |
Fatigue | 41 | 2 | 0 | 29 | 1 | 0 |
Pyrexia | 13 | <1 | 0 | 5 | 0 | 0 |
Additional adverse reactions occurring at an overall incidence of <10.0% of patients receiving IBRANCE plus fulvestrant in PALOMA-3 included asthenia (7.5%), aspartate aminotransferase increased (7.5%), dysgeusia (6.7%), epistaxis (6.7%), lacrimation increased (6.4%), dry skin (6.1%), alanine aminotransferase increased (5.8%), vision blurred (5.8%), dry eye (3.8%), and febrile neutropenia (0.9%).
Table 7. Laboratory Abnormalities in PALOMA-3Laboratory Abnormality | IBRANCE plus Fulvestrant (N=345) | Placebo plus Fulvestrant (N=172) |
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All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % |
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N=number of patients; WBC=white blood cells. |
WBC decreased | 99 | 45 | 1 | 26 | 0 | 1 |
Neutrophils decreased | 96 | 56 | 11 | 14 | 0 | 1 |
Anemia | 78 | 3 | 0 | 40 | 2 | 0 |
Platelets decreased | 62 | 2 | 1 | 10 | 0 | 0 |
Aspartate aminotransferase increased | 43 | 4 | 0 | 48 | 4 | 0 |
Alanine aminotransferase increased | 36 | 2 | 0 | 34 | 0 | 0 |