Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10760

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    P1.10-017 - Clinical activity of lurbinectedin (PM01183) in combination with gemcitabine (GEM) in non-small cell lung cancer (NSCLC) patients (pts): preliminary subgroup analysis of a phase Ib study. (ID 995)

    09:30 - 09:30  |  Author(s): I. Lopez Calderero
    • Abstract

    Background
    PM01183 is an inhibitor of transactivated transcription and also acts on the tumor microenvironment. It lacks cross-resistance with platinum (Pt) agents. Evidence of synergism with GEM has been observed preclinically. PM01183 is undergoing intensive clinical evaluation as single agent in phase II studies in pancreatic, ovarian, breast and NSCLC pts. Its primary side effects are reversible myelosuppression and high emetogenic potential.

    Methods
    Consenting adults with selected solid tumors (including NSCLC), age ≤ 75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, adequate major 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 when combined with GEM, both on Days 1 and 8 every three weeks (q3wk). Prior GEM was not allowed in the metastatic setting. Available results exclusively from the NSCLC population are described here.

    Results
    Recruitment was closed in December 2012. Overall, 22 of 45 treated pts (49%) had NSCLC. Of these, 73% were males. Median age was 65 years (r: 37-73). Patients received 1, 2 or 3 prior lines, in 64/27/9% of cases respectively. Non-squamous histology was reported in 91% of pts and 18% had known central nervous system (CNS) involvement. Five of 14 pts evaluable for efficacy by Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1, responded to therapy [4 PRs and 1 CR], reaching an overall response rate (ORR) of 36% [95% confidence interval (CI): 13-65] in the RECIST evaluable population. Median response duration was 31 weeks (r: 7-52+). Eight of 22 pts were not evaluated for efficacy, as this was not the primary endpoint of the phase Ib study. Nevertheless, on an intention-to treat basis the ORR was 23% (95%CI: 8-45). Severe myelosuppression, G3/4 neutropenia or thrombocytopenia, was observed in 67/42% of pts, respectively. Other toxicities, in ≥ 10% of pts, were generally mild and comprised anemia, ALT/AST or creatinine increases, fatigue, mucositis, nausea/vomiting and anorexia. No alopecia was reported. Serious adverse events included febrile neutropenia (FN), pneumonia, sepsis and shock, and resulted in two treatment-related deaths, both occurred at dose levels over the RD. The RD was established at PM01183 3.0 mg + GEM 800 mg/m[2] on Days 1 and 8 q3wk.

    Conclusion
    PM01183 and GEM combination resulted in relevant and durable clinical activity in NSCLC pts. Toxicity seems both manageable and predictable at the RD. The novel mechanism of action of PM01183, and particularly its lack of Pt cross-resistance are of special interest in this population. A randomized trial is ongoing to assess the role of this new CT combination in relapsed NSCLC.