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 [see Clinical Studies (14)]. 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 3 summarizes the adverse reactions in the SCLC cohort of Study B-005.
Clinically relevant adverse reactions in < 10% of patients who received ZEPZELCA include dysgeusia, febrile neutropenia and pneumonitis.
Table 4 summarizes the laboratory abnormalities in Study B-005.