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V. Moreno

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    MA 01 - SCLC: Research Perspectives (ID 650)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MA 01.05 - Activity and Safety of the Combination of PM01183 and Doxorubicin in Relapsed SCLC. Final Results of a Phase Ib Trial (ID 9249)

      11:00 - 12:30  |  Author(s): V. Moreno

      • Abstract
      • Presentation
      • Slides

      Lurbinectedin (PM01183) is a new anticancer drug that binds to DNA, inhibits transactivated transcription and modulates tumor microenvironment. Preclinical evidence of synergism was observed for PM01183 in combination with doxorubicin (DOX).

      Multicenter, phase I clinical trial to determine the recommended dose (RD) of the combination of PM01183 and DOX. An expansion cohort was recruited after finding striking activity in second-line small cell lung cancer (SCLC) patients. Due to hematological toxicity, the trial was amended to use a lower DOX dose and thus improve safety of the combination in selected indications. SCLC patients <75 years with ECOG performance status (PS) 0-1 and pretreated with no more than one chemotherapy line were included. Stable brain metastases were allowed. DOX was interrupted after 10 cycles and PM01183 could be continued as single-agent. Primary G-CSF prophylaxis was not mandatory.

      48 patients were treated: 21 in Cohort A (PM01183 3-5 mg flat dose [FD] Day (D)1 + DOX 50 mg/m2 D1 every 21 days [q21d]), and 27 in Cohort B (PM01183 2 mg/m2 D1 + DOX 40 mg/m2 D1 q21d). Males: 74%; median age: 64 (48-77) years, ECOG 0-1: 37%-63%; known central nervous system (CNS) involvement: 10%; bulky disease (>50 mm): 67%. 85% responded to first line, including 4% with complete response (CR). Median chemotherapy free interval (CTFI): 3.4 months. Refractory (CTFI<30 days) 23%; resistant (CTFI 30-90 days) 34%; sensitive (CTFI>90 days) 43%. RD: PM01183 4 mg FD (or 2 mg/m2) + DOX 50 mg/m2 D1 q21d. Confirmed ORR: 50% (95CI: 35-65%) with 6% CR in both cohorts; ORR=69% (95CI: 49-85%) with 10% CR in sensitive patients. Cohort A: ORR=67% (95%CI: 43-85%) with 10% CR; ORR=92% (95%CI: 62-100%) in sensitive patients. Cohort B: ORR=37% (95%CI: 19-58%) with 4% CR; ORR=53% (95%CI: 28-77%) in sensitive patients. Median PFS (mPFS) 4.6 months (95%CI: 3.1-5.8), with mPFS 1.5 months (95%CI: 1.2-3.8) in resistant patients and 5.8 months (95%CI: 3.6-7.9) in sensitive patients. In both cohorts, grade 4 neutropenia/anemia/thrombocytopenia appeared in 73%/4%/15% of patients and febrile neutropenia in 21% (11% at RD). Non-hematological toxicity was mainly fatigue (G3=14%) and nausea (G3=5%).

      PM01183/DOX combination showed remarkable activity as second line in SCLC, especially in patients with CTFI>90 days, regardless of dose. Activity is higher than reported for CAV or topotecan in this setting. Reversible myelosuppression was the most frequent and expected side effect. A phase III trial with this combination in relapsed SCLC is ongoing.

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