Table 1 Selected Completed Clinical Trials in patients with KRAS mutant NSCLC
From: KRAS mutant lung cancer: progress thus far on an elusive therapeutic target
Agent | Mechanism of action | Number of patients | Setting | Study results | References |
|---|---|---|---|---|---|
Farnesyl transferase inhibitor (R1155777) | Farnesyl transferase inhibitor | 44 (mutation status unknown) | Second line and beyond | No objective responses Median survival of 7.7 months | [25] |
Salirasib | Prevents localization of RAS to the plasma membrane | 33 (30 KRAS mutant) | All-lines | No observed responses; 11 patients with stable disease at 10 weeks (7 previously treated and 4 previously untreated) Median overall survival not reached | [28] |
Sorafenib | Tyrosine Kinase Inhibitor | 27 KRAS mutant | Second line and beyond | KRAS/BRAF marker group who were treated with sorafenib had a 79 % disease control rate at 8 weeks | [30] |
Sorafenib | Tyrosine Kinase Inhibitor | 37 (11 KRAS mutant) | Second line and beyond | Disease control rate of 65 % Median PFS of 3.4 months Median OS of 11.6 months 20 patients had stable disease and 2 had partial response | [31] |
MEK inhibitor | Selumetinib and Docetaxel | 87 (All KRAS mutant) | Second line and beyond | Median OS of 9.4 months in the selumetinib group compared to 5.2 months in placebo Median PFS was 5.3 months in the selumetinib group and 2.1 months in placebo | [36] |
MEK inhibitor | Trametinib | 129 (All KRAS mutant) | Second line and beyond | Median OS was 8 months in trametinib arm and not reached docetaxel arm Median PFS 3 months in trametinib group and 2.75 months in the docetaxel group 10 partial responses in trametinib group and 5 in docetaxel group | [38] |
CDK Inhibitor | LY2835219 | 49 (26 KRAS mutant) | Second line and beyond | Overall disease control rate of 51 %. In KRAS mutant NSCLC, DCR of 54 % versus 37 % in KRAS wild type. Median duration of SD was 5.6 months Median PFS was 2.1 months | [46] |