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C. Fernandez



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    P1.13 - Poster Session 1 - SCLC (ID 200)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.13-001 - Clinical activity of lurbinectedin (PM01183) in combination with doxorubicin (DOX) in small cell lung cancer (SCLC) patients (pts): preliminary results of a phase Ib study subpopulation analysis. (ID 954)

      09:30 - 09:30  |  Author(s): C. Fernandez

      • Abstract

      Background
      PM01183 is an inhibitor of transactivated transcription and also acts on the tumor microenvironment. It lacks cross-resistance with platinum (Pt) agents whereas strong synergism with DOX has been observed preclinically. Single agent PM01183 clinical evaluation in non-small cell lung cancer (NSCLC), pancreatic, ovarian and breast cancer patients (pts) is ongoing. Reversible myelosuppression and high emetogenic potential are common side effects.

      Methods
      Consenting adults with selected solid tumors, including SCLC, and ≤ 75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, adequate organ function and up to 2 prior chemotherapy-containing (CT) lines were included in successive cohorts aiming to primarily define the recommended dose (RD) of PM01183 and DOX (50 mg/m[2], fixed dose) combination every three weeks (q3wk). No prior DOX was allowed in the metastatic setting. DOX had to be discontinued once a maximal cumulative dose of 450 mg/m[2] during treatment was reached. Available results in the SCLC population are presented here.

      Results
      Recruitment was closed in December 2012; 13 of 43 enrolled/treated pts (30%) had SCLC diagnosis. Of these, 8 (62%) were males. Median age was 58 years (r: 48-73). Ten (77%) and 2 pts (15%) were chemo-refractory or had known central nervous system (CNS) involvement, respectively. Five of 12 pts evaluable for efficacy [Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1] were responders, for an overall response rate (ORR) of 42% [95% confidence interval (CI): 15-72]. No responses occurred in pts with >1 prior CT lines (n=5). In evaluable pts with 1 prior CT line (n=7), the ORR reached 71% (95%CI: 29-96). All chemosensitive pts (n=3) responded to treatment. Severe myelosuppression, G3/4 neutropenia or thrombocytopenia, was observed in 89/22% of pts, respectively. Other toxicities, in ≥ 10% of pts, were generally mild and included transaminase increases, fatigue, alopecia, mucositis, nausea/vomiting, diarrhea, anorexia and constipation. No cardiac toxicity was observed. Febrile neutropenia (FN) occurred in 11% of pts. Overall, 2 pts discontinued treatment due to toxicity (pneumonia; and repetitive myelosuppression despite successive dose adjustments, respectively). No treatment-related deaths occurred. The RD was defined as PM01183 4.0 mg and DOX 50 mg/m[2] q3wk.

      Conclusion
      PM01183 and DOX resulted in relevant activity in SCLC patients with less than 2 prior CT-lines. Toxicity with this combination seems both manageable and predictable. Despite the high level of myelosuppression, FN was relatively uncommon and colony-stimulating factors (CSFs) are not currently indicated. The novel mechanism of action, and particularly the lack of Pt cross-resistance, is of interest in this patient population. These results warrant further study of the potential role of this regimen in relapsed SCLC pts.