Secondary endpoint: progression-free survival (PFS)
CLICK THE TABS TO SEE INVESTIGATOR OR INDEPENDENT REVIEW COMMITTEE (IRC) ASSESSMENTS
Kaplan-Meier plot of PFS by Investigator Assessment1,2,a
| Overall | 105 | 69 | 43 | 27 | 14 | 7 | 5 | 4 | 2 | 1 | 0 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CTFI <90 | 45 | 22 | 12 | 7 | 3 | 2 | 1 | 1 | 1 | 1 | 0 |
| CTFI ≥90 | 60 | 47 | 31 | 20 | 11 | 5 | 4 | 3 | 1 | 0 | 0 |
| Time (months) | Overall | CTFI <90 | CTFI ≥90 |
|---|---|---|---|
| 0 | 105 | 45 | 60 |
| 2 | 69 | 22 | 47 |
| 4 | 43 | 12 | 31 |
| 6 | 27 | 7 | 20 |
| 8 | 14 | 3 | 11 |
| 10 | 7 | 2 | 5 |
| 12 | 5 | 1 | 4 |
| 14 | 4 | 1 | 3 |
| 16 | 2 | 1 | 1 |
| 18 | 1 | 1 | 0 |
| 20 | 0 | 0 | 0 |
Kaplan-Meier plot of PFS by IRC Assessment1,2,a
| Overall | 105 | 59 | 37 | 21 | 10 | 4 | 2 | 2 | 2 | 1 | 0 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CTFI <90 | 45 | 17 | 9 | 4 | 1 | 1 | 1 | 1 | 1 | 1 | 0 |
| CTFI ≥90 | 60 | 42 | 28 | 17 | 9 | 3 | 1 | 1 | 1 | 0 | 0 |
| Time (months) | Overall | CTFI <90 | CTFI ≥90 |
|---|---|---|---|
| 0 | 105 | 45 | 60 |
| 2 | 59 | 17 | 42 |
| 4 | 37 | 9 | 28 |
| 6 | 21 | 4 | 17 |
| 8 | 10 | 1 | 9 |
| 10 | 4 | 1 | 3 |
| 12 | 2 | 1 | 1 |
| 14 | 2 | 1 | 1 |
| 16 | 2 | 1 | 1 |
| 18 | 1 | 1 | 0 |
| 20 | 0 | 0 | 0 |
a PFS was defined as time from the date of first infusion to disease progression, death from any cause, or last tumor evaluation. At data cutoff (Jan 15, 2019), median follow-up was 17.1 months (IQR 6.5–25.3).
Limitations of Data
PFS was a secondary endpoint assessed in the phase 2, single-arm trial for ZEPZELCA that is not reflected in the full Prescribing Information and was not powered to assess PFS efficacy.
b This subgroup analysis was not powered to determine statistical significance. Results are descriptive only.
CTFI=chemotherapy-free interval; IQR=interquartile range.STUDY DESIGN1,3
The phase 2 study was a multicenter, open-label, multi-cohort trial evaluating ZEPZELCA as a single agent in 105 adult patients with advanced or metastatic SCLC with disease progression on or after platinum-based chemotherapy. Patients received ZEPZELCA 3.2 mg/m2 by intravenous infusion every 21 days (one cycle) for a median of 4 cycles (range: 1 to 24 cycles). The median age was 60 years (range: 40 to 83 years). Baseline ECOG PS was 0–1 in 92% of patients. The major efficacy outcome measure was confirmed investigator-assessed ORR. Additional efficacy outcome measures included duration of response and IRC-assessed ORR using Response Evaluation Criteria in Solid Tumors v1.1.
ECOG PS=Eastern Cooperative Oncology Group Performance Status; ORR=overall response rate; SCLC=small cell lung cancer.See Dr. Socinski explain the safety profile for ZEPZELCA
Secondary endpoint
VIEW OVERALL SURVIVALIMPORTANT 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.