Acute Myeloid Leukemia
The safety of ONUREG was evaluated in QUAZAR [see Clinical Studies (14)]. Patients received ONUREG 300 mg (N=236) or placebo (N=233) orally once daily on Days 1 through 14 of each 28-day cycle. Among patients who received ONUREG, 71% were exposed for 6 months or longer, and 49% were exposed for greater than one year. The median duration of exposure to ONUREG was 11.6 months (range: 0.5 to 74.3 months) and the median number of cycles was 12 (range: 1 to 82 cycles).
Serious adverse reactions occurred in 15% of patients who received ONUREG. Serious adverse reactions in ≥ 2% of patients who received ONUREG were pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received ONUREG.
Permanent discontinuation of ONUREG due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ONUREG in > 1% of patients included nausea (2.1%), diarrhea (1.7%), and vomiting (1.3%). Interruptions of ONUREG due to an adverse reaction occurred in 35% of patients. Adverse reactions which required an interruption of ONUREG in > 5% of patients included neutropenia (20%), thrombocytopenia (8%), and nausea (6%).
Dose reductions of ONUREG due to an adverse reaction occurred in 14% of patients. Adverse reactions which required a dose reduction in > 1% of patients included neutropenia (6%), diarrhea (3.4%), thrombocytopenia (1.7%), and nausea (1.7%).
The most common (≥ 10%) adverse reactions were nausea, vomiting, diarrhea, fatigue/asthenia, constipation, upper respiratory tract infection, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, skin infection, and pain in extremity.
Table 2 summarizes the adverse reactions in QUAZAR.
Table 2: Adverse Reactions (≥ 5%) in Patients with AML Who Received ONUREG with a Difference Between Arms of > 2% Compared to Placebo in QUAZAR| Adverse Reaction | ONUREG (N=236) | Placebo (N=233) |
|---|
All Grades (%) | Grade 3 or 4 (%) | All Grades (%) | Grade 3 or 4 (%) |
|---|
a Grouped term includes abdominal pain, abdominal pain upper, abdominal discomfort, and gastrointestinal pain.
b Grouped term includes fatigue and asthenia.
c Broad scope term includes acute sinusitis, adenoviral upper respiratory infection, chronic tonsillitis, influenza, nasopharyngitis, pharyngitis, rhinitis, sinusitis, sinusitis fungal, tonsillitis, tracheitis, upper respiratory tract infection, upper respiratory tract infection bacterial, viral pharyngitis, viral rhinitis, viral upper respiratory tract infection. |
| d Broad scope term includes influenza, pneumonia, respiratory tract infection, respiratory tract infection viral, bronchopulmonary aspergillosis, lung infection, Staphylococcal infection, atypical pneumonia, lower respiratory tract infection, lung abscess, Pneumocystis jirovecii pneumonia, pneumonia bacterial, pneumonia fungal, Pseudomonas infection, hemoptysis, productive cough, pleural effusion, atelectasis, pleuritic pain, rales, Enterobacter test positive, and Hemophilus test positive. |
Gastrointestinal disorders |
Nausea | 65 | 3 | 24 | < 1 |
Vomiting | 60 | 3 | 10 | 0 |
Diarrhea | 50 | 5 | 21 | 1 |
Constipation | 39 | 1 | 24 | 0 |
Abdominal paina
| 22 | 2 | 13 | < 1 |
General disorders and administration site conditions |
Fatigue / astheniab
| 44 | 4 | 25 | 1 |
Infections |
Upper respiratory tract infectionc
| 34 | 2 | 28 | 0 |
Pneumoniad
| 27 | 9 | 17 | 5 |
Skin infectione
| 11 | 3 | 8 | 1 |
Sepsisf
| 6g
| 5 | 3 | 3 |
Musculoskeletal and connective tissue disorders |
Arthralgia | 14 | 1 | 10 | < 1 |
Pain in extremity | 11 | < 1 | 5 | 0 |
Metabolism and nutrition disorders |
Decreased appetite | 13 | 1 | 6 | 1 |
Blood and lymphatic disorders |
Febrile neutropenia | 12 | 11 | 8 | 8 |
Nervous system disorders |
Dizziness | 11 | 0 | 9 | 0 |
e Broad scope term includes cellulitis, erythema migrans, folliculitis, fungal skin infection, furuncle, herpes simplex, herpes zoster, nail bed infection, nail infection, onychomycosis, skin infection, staphylococcal skin infection.
f Grouped term includes: Sepsis, bacterial sepsis, neutropenic sepsis, device related sepsis, Klebsiella sepsis, Septic shock, Staphylococcal sepsis, and urosepsis.
g Includes 1 fatal adverse reaction.
Clinically relevant adverse reactions in less than 5% of patients who received ONUREG included
Investigations: Weight decreased
Neutropenia, thrombocytopenia, and anemia of any grade occurred in 74%, 65%, and 25% of patients who received ONUREG. Table 3 summarizes select Grades 3 or 4 hematological laboratory abnormalities in QUAZAR.
Table 3: Selected Hematological Laboratory Abnormalities That Worsened from Baseline in Patients Who Received ONUREG in QUAZAR | ONUREG | Placebo |
|---|
| Laboratory Abnormality | Baseline Grade 0-2 N | Post-Baseline Grade 3 or 4 n (%) | Baseline Grade 0-2 N | Post-Baseline Grade 3 or 4 n (%) |
|---|
Neutropenia | 223 | 109 (49) | 217 | 50 (23) |
Thrombocytopenia | 222 | 46 (21) | 212 | 22 (10) |
Anemia | 229 | 10 (4) | 223 | 7 (3) |