Figures
- FIGURE 1
Main genomic features of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS)-mutated nonsmall cell lung cancer (NSCLC). EGFR: epidermal growth factor receptor.
Tables
- TABLE 1
Clinical outcomes related to evaluated drugs in KRAS-mutated nonsmall cell lung cancer patients
Trial arm [ref.] Patients Previous lines ORR % DCR % Median PFS months Median OS months MAPK pathway Salirasib [24] 33 Any 0 33.3 Sorafenib [25] 10 ≥1 33.3 60 3 Sorafenib [26] 59 ≥1 8.5 50.8 2.3 5.3 Sorafenib 34 ≥2 2.9 44.1 2.6 6.4 versus placebo [27] 34 ≥2 0 7.6 1.7 (HR 0.46, 95% CI 0.25–0.82; p=0.007) 5.1 (HR 0.76, 95% CI 0.45–1.26; p=0.279) Sorafenib 14 ≥1 79 versus erlotinib 7 ≥1 14 versus erlotinib + bexarotene 3 ≥1 33 versus vandetanib [28] 14 ≥1 0 Selumetinib 9 ≥1 0 3.9 versus selumetinib + erlotinib [29] 30 ≥1 6.7 4.5 Selumetinib + docetaxel 44 ≥1 36.4 80 5.3 9.4 versus docetaxel + placebo [30] 43 ≥1 0 46.5 2.1 (HR 0.58, 95% CI 0.42–0.79; p=0.014) 5.2 (HR 0.8, 95% CI 0.56–1.14; p=0.21) Trametinib 86 1 11.6 90.7 3 8 versus docetaxel [31] 43 1 11.6 74.4 2.8 (HR 1.23, 95% CI 0.81–1.87; p=0.316) Unreached (HR 0.97, 95% CI 0.52–1.83; p=0.934) Trametinib + docetaxel [32] 22 ≥1 13.6 61 Trametinib + pemetrexed [33] 20 ≥1 75 65 mTOR inhibitors Ridaforolimus [34] 79 ≥1 35.4 Ridaforolimus 14 ≥1 sd
after 8 weeks ridaforolimus4 18 versus placebo [34] 14 ≥1 sd
after 8 weeks ridaforolimus2 (HR 0.36, p=0.013) 5 (HR 0.46, p=0.09) Hsp90 inhibitor Ganetespib [35] 17 ≥1 0 35 1.9 11.0 Data are presented as n, unless otherwise stated. ORR: objective response rate; DCR: disease control rate; PFS: progression-free survival; OS: overall survival; MAPK: mitogen-activated protein kinase; mTOR: mammalian target of rapamycin; Hsp90: heat shock protein 90; HR: hazard ratio.
- TABLE 2
Ongoing clinical trials performed in KRAS-mutated nonsmall cell lung (NSCLC) patients
clinicaltrials.gov identifier Phase Tumour type MEK inhibitors Selumetinib + docetaxel (versus docetaxel) NCT01933932 III NSCLC Trametinib + chemoradiation NCT01912625 I Unresectable NSCLC PD-0325901 + palbociclib NCT02022982 I/II NSCLC and other solid tumours MEK162 + BYL719 NCT01449058 Ib All solid tumours MEK162 NCT01885195 II All solid and haematological malignancies MEK162 + RAF265 NCT01352273 I All solid tumours MEK162 + erlotinib NCT01859026 I NSCLC PD-0325901 + dacomitinib NCT02039336 I NSCLC Other BIND-014 NCT02283320 II NSCLC Bortezomib NCT01833143 II NSCLC Retaspimycin HCI (IPI-504) + everolimus NCT01427946 Ib/II NSCLC VS-6063 (defactinib) NCT01951690 II NSCLC Wild-type reovirus + paclitaxel + carboplatin NCT00861627 II NSCLC Abemaciclib (LY2835219) NCT02152631 III NSCLC
Vol 25 Issue 139
Table of Contents
KRAS oncogene in lung cancer: focus on molecularly driven clinical trials
