Author of

• 12648

  +

  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

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

  • 12685

    +

    P3.11-037 - A phase II study of sorafenib and metformin in patients with stage IV non-small cell lung cancer (NSCLC) with a KRAS mutation (ID 2701)

    09:30 - 09:30  |  Author(s): W.W. Mellema
    • Abstract

    Background
    Previously we reported a phase II study of sorafenib, a multi tyrosine kinase inhibitor, in advanced NSCLC patients with a KRAS mutation [1]. While sorafenib was found active in this group of patients, progression free survival (PFS) and overall survival (OS) were disappointing. Concurrent inhibition of multiple pathways may improve treatment outcome. Metformin is a save and well known antidiabetic drug. It has been described that metformin has inhibitory effects against mTOR, downstream of PI3K. An in vitro study of our group has shown synergistic effects of sorafenib and metformin which provided the rationale for this study [2]. In a post hoc analysis of the previous study, metformin users appeared to be among the longest survivors.

    Methods
    Patients with advanced NSCLC with a KRAS mutation, pretreated with platinum containing chemotherapy were included. Other inclusion criteria were: ECOG performance score (PS) 0-1, adequate organ reserve, creatinine clearance >60 ml/min and provided written informed consent according to local IRB regulations. A tumor biopsy was mandatory to confirm the presence of a KRAS mutation, prior to start of treatment. Treatment consisted of sorafenib 400 mg BID and metformin 1000 mg BID until disease progression or unacceptable toxicity. Dose reductions and discontinuations were specified per protocol in the face of CTC toxicities grade 3 and 4. Primary endpoint: disease control rate (DCR) at 6 weeks according to RECIST version 1.1. Secondary endpoints: duration of response, progression free survival (PFS), overall survival and treatment related toxicities. A 2-stage design was implemented (Simon's optimal design; p0=50%, p1=70%, alpha=0.05, beta=0.20) for a total of 45 evaluable patients.

    Results
    Fifty-five patients were included between 1[st] of July 2012 and 1[st] of June 2013. Median age was 60 (range 34-77) years, 28 female (51 %), ECOG PS 0/1/2 16/32/1, all patients had stage IV disease. Of 47 patients disease evaluation after 6 weeks was available (Fig. 1). Two patients had a partial response, 23 stable disease and 22 patients had progressive disease. DCR was 53%. Results of secondary endpoints will be available at time of the conference.

    Conclusion
    This preliminary analysis suggests that the addition of metformin did not improve DCR, compared to previous reported results of sorafenib monotherapy in pretreated stage IV NSCLC patients with a KRAS mutation. [1] Dingemans AM et al. Clin Cancer Res. 2013 Feb 1;19(3):743-51 [2] Groenendijk FH et al. EJC. 2012 Nov; 48 (suppl. 6): p 48 Figure 1