Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of LIFYORLI in combination with nab-paclitaxel was evaluated in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in ROSELLA [see Clinical Studies (14)].
Patients received LIFYORLI (150 mg orally on the day before, the day of, and the day after each administration of nab-paclitaxel 80 mg/m2 intravenous infusion on Days 1, 8 and 15 of each 28-day cycle (n=188) or nab-paclitaxel 100 mg/m2 intravenous infusion (n=190) until disease progression or unacceptable toxicity. LIFYORLI dosing was interrupted whenever nab-paclitaxel was interrupted. The median duration of LIFYORLI treatment was 4.7 months (range: 0.2 to 24).
Serious adverse reactions occurred in 35% of patients who received LIFYORLI in combination with nab-paclitaxel. Serious adverse reactions in ≥2% of patients were neutropenia (4%), pneumonia (3.2%), pleural effusion (3.2%), febrile neutropenia (2.1%), and fatigue (2.1%). Fatal adverse reactions occurred in 2.1% of patients who received LIFYORLI in combination with nab-paclitaxel including septic shock (0.5%), cardiac arrest (0.5%), ischemic stroke (0.5%), and intestinal perforation (0.5%).
Permanent discontinuation of LIFYORLI in combination with nab-paclitaxel due to adverse reactions occurred in 9% of patients. The adverse reaction which resulted in permanent discontinuation of LIFYORLI in >2% of patients was intestinal obstruction (2.6%).
Dosage interruptions of LIFYORLI due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruptions of LIFYORLI in combination with nab-paclitaxel in ≥5% of patients included neutropenia (44%), anemia (12%), and fatigue (7%).
Dose reductions of LIFYORLI due to an adverse reaction occurred in 7.4% of patients and dose reductions of nab-paclitaxel occurred in 48% of patients. Adverse reactions which required dose reductions of LIFYORLI included fatigue (1.6%), decreased appetite (1.2%), abdominal pain (0.5%), neutropenia (0.5%), edema (0.5%), and sciatica (0.5%).
The most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash, and decreased appetite.
Table 5 and 6 summarize adverse reactions and laboratory abnormalities, respectively, occurring in ≥10% of patients who received LIFYORLI in combination with nab-paclitaxel in ROSELLA.
Table 5: Adverse Reactions Occurring in ≥10% of Patients Who Received LIFYORLI in Combination with Nab-Paclitaxel in ROSELLA
|
| Adverse Reaction | LIFYORLI + Nab-Paclitaxel (n=188) | Nab-Paclitaxel (n=190) |
| All Grades (%) | Grades 3 or 4 (%) | All Grades (%) | Grades 3 or 4 (%) |
| General disorders |
| Fatiguea
| 54
| 9
| 45
| 1.6
|
| Edemaa
| 19
| 1.1
| 12
| 0.5
|
| Pyrexiaa
| 14
| 0.5
| 9
| 0
|
| Gastrointestinal disorders | | | | |
| Nausea
| 44
| 4
| 35
| 3
|
| Diarrheaa
| 40
| 3.7
| 27
| 1.6
|
| Stomatitisa
| 19
| 3.2
| 9
| 1.1
|
| Skin and subcutaneous tissue disorders |
| Rasha
| 24
| 3.7
| 10
| 0.5
|
| Nail disordersa
| 19
| 0
| 12
| 2
|
| Metabolism and nutrition disorders |
| Decreased appetite
| 22
| 1.6
| 12
| 0.5
|
| Respiratory disorders | | | | |
| Cougha
| 19
| 0.5
| 10
| 0
|
| Nervous system disorders |
| Dizzinessa
| 13
| 0.5
| 4
| 0.5
|
| Dysgeusiaa
| 13
| 0
| 5
| 0
|
Clinically relevant adverse reactions occurring in <10% of patients who received LIFYORLI in combination with nab-paclitaxel in ROSELLA included dry eye (8.5%), hypotension (8.5%), hypertension (4.8%), acute kidney injury (4.3%), febrile neutropenia (3.7%), and syncope (2.7%).
Table 6: Select Laboratory Abnormalities ≥10% for All Grades, in Patients Who Received LIFYORLI in Combination with Nab-Paclitaxel in ROSELLA
| Laboratory Abnormality | LIFYORLI + Nab-Paclitaxel (n=188) | Nab-Paclitaxel (n=190) |
All Grades (%) | Grades 3 or 4 (%) | All Grades (%) | Grades 3 or 4 (%) |
| Hemoglobin decreased
| 89
| 18
| 79
| 10
|
| Leukocytes decreased
| 82
| 25
| 77
| 16
|
| Neutrophils decreased
| 74
| 44
| 65
| 27
|
| Platelets decreased
| 28
| 2
| 14
| 1
|