A phase II study of sorafenib in patients with platinum pretreated, advanced (stage IIIb or IV) non-small cell lung cancer with a KRAS mutation
Mené sur 57 patients atteints d'un cancer du poumon non à petites cellules de stade IIIb ou IV présentant des mutations du gène KRAS, cet essai de phase II évalue, du point de vue du taux de contrôle de la maladie à 6 semaines, le sorafenib après l'échec d'un traitement aux sels de platine
Purpose. Sorafenib inhibits the Ras-Raf pathway, which is overactive in patients with a KRAS mutation. We hypothesized that NSCLC patients with KRAS mutation will benefit from treatment with sorafenib. Methods: In this phase II study, patients with KRAS mutated, stage IIIb or IV NSCLC that progressed after at least 1 platinum containing regimen were treated with sorafenib. Treatment consisted of sorafenib 400 mg BID until disease progression or unacceptable toxicity. Pretreatment serum from each patient was obtained to predict outcome using a proteomic assay (VeriStrat). Primary endpoint: Disease control rate (DCR) at 6 weeks. Results: 59 patients were entered between May 2010 and February 2011. 57 patients started sorafinib. Mean age was 58.5 (SD ± 8.1) years, 16 Male / 41 Female, ECOG PS 0/1/2 24/30/3. At 6 weeks 5 partial response, 25 stable disease, 27 progressive disease were observed; DCR was 52.6%. Median duration of treatment was 9 weeks. The median PFS was 2.3 months, median OS was 5.3 months. Patients with a prediction of good prognosis according to Veristrat serum proteomics assay showed a significant superior PFS (HR= 1.4; 95% CI. 1.0-1.9), but not OS (HR= 1.3; 95% CI. 0.9-1.7). Sorafenib related grade 3-4 toxicity was reported in 10 patients (17.5%), all but 1 patient experienced grade 3 skin toxicity (14.0%) or grade 3 gastrointestinal toxicity (8.8%). Conclusion: Treatment with sorafenib has relevant clinical activity in NSCLC patients harboring KRAS mutations. Further randomized study with this agent is warranted as single agent or combination therapy.