Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

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

  • 10842

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    P1.11-042 - SORAVE: Sorafenib and everolimus for patients with solid tumors and with KRAS mutated NSCLC - results of a phase I study. (ID 3068)

    09:30 - 09:30  |  Author(s): R. Schnell
    • Abstract

    Background
    Inhibition of signaling pathways interfering with cell proliferation and angiogenesis may increase anti-tumor efficacy. Sorafenib as well as mTOR inhibitors showed preliminary activity in KRAS mutated NSCLC.

    Methods
    In the dose escalation part, patients with relapsed solid tumors were treated with escalating doses of everolimus from 2.5-10.0 mg daily p.o. in a 14 days run-in phase followed by the combination with a fixed dose of sorafenib 400 mg bid p.o. The extension phase is currently recruiting patients with KRAS mutated NSCLC. The KRAS mutation status is determined by PCR based high resolution melting curve analysis (HRM) on DNA extracted from FFPE material and validated using Sanger sequencing. HRM has now been replaced by multiplex PCR. Pharmacokinetic (PK) analyses are performed during run-in and during the combination. Treatment outcome is validated with CT scans on day 57.

    Results
    In the dose escalation part, 19 patients were recruited. The dose limiting toxicity (DLT) was not reached. At everolimus dose level of 10 mg/day, increased rates of grade 3 thrombocytopenia (3 patients), leukocytopenia (2 patients) and anaemia (2 patients) occurred after the DLT interval of 29 days. Based on these observations, the dose level of 7.5 mg/day everolimus in combination with 400 mg sorafenib bid was defined as a maximal tolerated dose. The AUC and Cmax values of everolimus at all dose levels were comparable on days 5 and 14. On day 29, AUC and Cmax of everolimus showed a 20 - 40% reduction when co-administered with sorafenib. The best treatment outcome on day 57 was stable disease in 11 patients. Median PFS and OS were 3.7 and 5.5 months, respectively. The extension phase in KRAS mutated NSCLC is currently ongoing. Nine patients have been recruited so far. The CT response at day 57 compared to the baseline of four evaluable patients is ranging from -22% to +5% in the sum of the longest diameter of all targeted lesions.

    Conclusion
    Treatment of patients with relapsed solid tumors with the combination of 7.5 mg everolimus p.o. daily and 400 mg sorafenib p.o. bid is safe and feasible. Current results of an extension phase in KRAS mutated NSCLC patients show preliminary clinical activity in this patient group with an unfavorable prognosis.