3 years in clinical use:ZEPZELCA has an established safety profile

Most adverse reactions were1,2Grade 1 OR 2

  • 1.9% of patients (2 of 105) permanently discontinued due to adverse reactions1
    • Adverse reactions resulting in permanent discontinuation in ≥1% of patients included peripheral neuropathy and myelosuppression
  • Dose reductions due to an adverse reaction occurred in 25% of patients1
    • Adverse reactions requiring dosage reductions in ≥3% of patients included neutropenia, febrile neutropenia, and fatigue
  • Dose interruptions due to an adverse reaction occurred in 30.5% of patients1
    • Adverse reactions requiring dosage interruptions in ≥3% of patients included neutropenia and hypoalbuminemia

Adverse Reactions (≥10%) in Patients with SCLC1

Adverse reaction ZEPZELCA (N=105)
All
Gradesa,b
(%) 		Grades
3–4 (%)
General disorders
Fatigue7712
Pyrexia130
Chest pain100
Gastrointestinal disorders
Nausea 370
Constipation 310
Vomiting 220
Diarrhea 204
Abdominal painc111
Musculoskeletal and connective tissue disorders
Musculoskeletal paind334
Metabolism and nutrition disorders
Decreased appetite331
Respiratory, thoracic, and mediastinal disorders
Dyspnea316
Coughe200
Infections and infestations
Respiratory tract infectionf185
Pneumoniag107
Nervous system disorders
Peripheral neuropathyh111
Headache101

a Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (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.

  • Alopecia occurred in 1% of patients2

Select Laboratory Abnormalities (≥20%) Worsening From Baseline1

Laboratory abnormalities ZEPZELCA (N=105)
All
Gradesa,b
(%) 		Grades
3–4 (%)
Hematology
Decreased leukocytes 7929
Decreased lymphocytes 7943
Decreased hemoglobin 7410
Decreased neutrophils 7146
Decreased platelets 377
Chemistry
Increased creatinine 690
Increased alanine aminotransferase 664
Increased glucose 525
Decreased albumin 321
Decreased sodium 317
Increased aspartate aminotransferase 262
Decreased magnesium 220

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.

  • In the phase 2 study, 22% of patients received granulocyte colony-stimulating factor (G-CSF) for secondary prophylaxis or therapy for neutropenia, but primary prophylaxis was not allowed.1,3

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IMPORTANT SAFETY INFORMATION

Myelosuppression

ZEPZELCA can cause myelosuppression. In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA, Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients.

Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.

Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3.

Monitor blood counts including neutrophil count and platelet count prior to each administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

Hepatotoxicity

ZEPZELCA can cause hepatotoxicity. In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA, Grade 3 elevations of ALT and AST were observed in 6% and 3% of patients, respectively, and Grade 4 elevations of ALT and AST were observed in 0.4% and 0.5% of patients, respectively. The median time to onset of Grade ≥3 elevation in transaminases was 8 days (range: 3 to 49), with a median duration of 7 days.

Monitor liver function tests prior to initiating ZEPZELCA, periodically during treatment, and as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

Extravasation Resulting in Tissue Necrosis

Extravasation of ZEPZELCA resulting in skin and soft tissue injury, including necrosis requiring debridement, can occur. Consider use of a central venous catheter to reduce the risk of extravasation, particularly in patients with limited venous access. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion.

If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary.

Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation.

Rhabdomyolysis

Rhabdomyolysis has been reported in patients treated with ZEPZELCA.

Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity.

Embryo-Fetal Toxicity

ZEPZELCA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose.

Lactation

There are no data on the presence of ZEPZELCA in human milk, however, because of the potential for serious adverse reactions from ZEPZELCA in breastfed children, advise women not to breastfeed during treatment with ZEPZELCA and for 2 weeks after the last dose.

MOST COMMON ADVERSE REACTIONS

The most common adverse reactions, including laboratory abnormalities, (≥20%) are leukopenia (79%), lymphopenia (79%), fatigue (77%), anemia (74%), neutropenia (71%), increased creatinine (69%), increased alanine aminotransferase (66%), increased glucose (52%), thrombocytopenia (37%), nausea (37%), decreased appetite (33%), musculoskeletal pain (33%), decreased albumin (32%), constipation (31%), dyspnea (31%), decreased sodium (31%), increased aspartate aminotransferase (26%), vomiting (22%), decreased magnesium (22%), cough (20%), and diarrhea (20%).

DRUG INTERACTIONS

Effect of CYP3A Inhibitors and Inducers

Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and Seville oranges) as this increases lurbinectedin systemic exposure which may increase the incidence and severity of adverse reactions to ZEPZELCA. If coadministration cannot be avoided, reduce the ZEPZELCA dose as appropriate.

Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.

GERIATRIC USE

Of the 105 patients with SCLC administered ZEPZELCA in clinical studies, 37 (35%) patients were 65 years of age and older, while 9 (9%) patients were 75 years of age and older. No overall difference in effectiveness was observed between patients aged 65 and older and younger patients.

There was a higher incidence of serious adverse reactions in patients ≥65 years of age than in patients <65 years of age (49% vs 26%, respectively). The serious adverse reactions most frequently reported in patients ≥65 years of age were related to myelosuppression and consisted of febrile neutropenia (11%), neutropenia (11%), thrombocytopenia (8%), and anemia (8%).

Please see accompanying full Prescribing Information.

INDICATION

ZEPZELCA® (lurbinectedin) is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Myelosuppression

ZEPZELCA can cause myelosuppression. In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA, Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients.

Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.

Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3.

Monitor blood counts including neutrophil count and platelet count prior to each administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

References: 1. ZEPZELCA (lurbinectedin) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2. Data on file. LUR-2020-003. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 3. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645–654.