ZEPZELCA SIDE EFFECTS
- Generic Name: lurbinectedin for injection
- Brand Name: Zepzelca
- Drug Class: Antineoplastics, Alkylating
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Myelosuppression
- Hepatotoxicity
Clinical Trials Experience
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 pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to ZEPZELCA as a single agent at a dose of 3.2 mg/m2 intravenously every 21 days in 554 patients with advanced solid tumors. Among 554 patients who received ZEPZELCA, including 105 patients with small cell lung cancer (SCLC) in PM1183-B-005-14 (Study B-005), 24% were exposed for 6 months or longer and 5% were exposed for greater than one year.
Small Cell Lung Cancer (SCLC)
The safety of ZEPZELCA was evaluated in a cohort of 105 patients with previously treated SCLC in Study B-005. Patients received ZEPZELCA 3.2 mg/m2 intravenously every 21 days. All patients in this study received a pre-specified anti-emetic regimen consisting of a corticosteroid and serotonin antagonist. Patients could receive G-CSF for secondary prophylaxis (i.e., after patients had an initial decrease in WBC), but not primary prophylaxis. Among patients who received ZEPZELCA, 29% were exposed for 6 months or longer and 6% were exposed for greater than one year.
Serious adverse reactions occurred in 34% of patients who received ZEPZELCA. Serious adverse reactions in ≥ 3% of patients included pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anemia, dyspnea, and thrombocytopenia.
Permanent discontinuation due to an adverse reaction occurred in two patients (1.9%) who received ZEPZELCA. Adverse reactions resulting in permanent discontinuation in ≥ 1% of patients who received ZEPZELCA, which included peripheral neuropathy and myelosuppression.
Dosage interruptions due to an adverse reaction occurred in 30.5% of patients who received ZEPZELCA. Adverse reactions requiring dosage interruption in ≥ 3% of patients who received ZEPZELCA included neutropenia, and hypoalbuminemia.
Dose reductions due to an adverse reaction occurred in 25% of patients who received ZEPZELCA. Adverse reactions requiring dosage reductions in ≥ 3% of patients who received ZEPZELCA included neutropenia, febrile neutropenia and fatigue.
The most common adverse reactions, including laboratory abnormalities, (≥ 20%) were leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea.
Table 1 summarizes the adverse reactions in the SCLC cohort of Study B-005.
Table 1: Adverse Reactions (≥ 10%) in Patients With SCLC Who Received ZEPZELCA in Study B-005
| Adverse Reaction | ZEPZELCA (n=105) |
|
| All Gradesa,b (%) | Grades 3-4 (%) | |
| General disorders | ||
| Fatigue | 77 | 12 |
| Pyrexia | 13 | 0 |
| Chest pain | 10 | 0 |
| Gastrointestinal disorders | ||
| Nausea | 37 | 0 |
| Constipation | 31 | 0 |
| Vomiting | 22 | 0 |
| Diarrhea | 20 | 4 |
| Abdominal painc | 11 | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal paind | 33 | 4 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 33 | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 31 | 6 |
| Coughe | 20 | 0 |
| Infections and infestations | ||
| Respiratory tract infectionf | 18 | 5 |
| Pneumoniag | 10 | 7 |
| Nervous system disorders | ||
| Peripheral neuropathyh | 11 | 1 |
| Headache | 10 | 1 |
| a Graded per NCI CTCAE 4.0. b No grade 5 adverse reactions were reported. c Includes abdominal pain, abdominal pain upper and abdominal discomfort. d Includes musculoskeletal pain, back pain, arthralgia, pain in extremity, musculoskeletal chest pain, neck pain, bone pain and myalgia. e Includes cough and productive cough. f Includes upper respiratory tract infection, viral upper respiratory tract infection, respiratory tract infection and bronchitis. g Includes pneumonia and lung infection. h Includes neuropathy peripheral, neuralgia, paresthesia, peripheral sensory neuropathy, hypoesthesia, and hyperesthesia. |
||
Clinically relevant adverse reactions in < 10% of patients who received ZEPZELCA include dysgeusia, febrile neutropenia and pneumonitis.
Table 2 summarizes the laboratory abnormalities in Study B-005.
Table 2: Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline in Patients With SCLC Who Received ZEPZELCA in Study B-005
| Laboratory Abnormality | ZEPZELCAa (n=105) |
|
| All Gradesb (%) | Grades 3-4 (%) | |
| Hematology | ||
| Decreased leukocytes | 79 | 29 |
| Decreased lymphocytes | 79 | 43 |
| Decreased hemoglobin | 74 | 10 |
| Decreased neutrophils | 71 | 46 |
| Decreased platelets | 37 | 7 |
| Chemistry | ||
| Increased creatinine | 69 | 0 |
| Increased alanine aminotransferase | 66 | 4 |
| Increased glucose | 52 | 5 |
| Decreased albumin | 32 | 1 |
| Decreased sodium | 31 | 7 |
| Increased aspartate aminotransferase | 26 | 2 |
| Decreased magnesium | 22 | 0 |
| a The denominator used to calculate the rate varied from 95 to 105 based on the number of patients with a baseline value and at least one post-treatment value. b Graded per NCI CTCAE 4.0. |
||
SRC: NLM .