Table 2.
Completed clinical trials of chemotherapy + MEK inhibitors in NSCLC
| Study | Study design | Intervention | Comparation | Patient population | Patients (n) | Median OS (months) | Median PFS (months) | ORR (%) |
|---|---|---|---|---|---|---|---|---|
| Jänne et al. [43] | Phase2 (NCT00890825) | Selumetinib + docetaxel | Placebo + docetaxel | KRAS-mutant advanced NSCLC | 87 (44 vs 43) | 9.4 vs 5.2 (HR:0.8, 80% CI = 0.56–1.14, P = 0.21) | 5.3 vs 2.1 (HR:0.58, 80%CI = 0.42–0.79, P = 0.014) | 37% vs 0 |
| Gandara et al. [46] | Phase1 (NCT01192165) | Trametinib + docetaxel | Trametinib + pemetrexed | NSCLC | 95 (49 vs 46) | NA |
KRAS wild-type:4.2 vs 5.8 KRAS-mutant type: 3.4 vs 4 |
KRAS wild-type:18% vs 11% KRAS-mutant type: 24% vs 17% |
| Jänne et al. [47] | Phase1 (NCT01933932) | Selumetinib + docetaxel | Placebo + docetaxel | KRAS-mutant NSCLC | 510 (251 VS 254) | 8.7 VS 7.9 (HR:1.05, 95% = 0.85–1.30, P = 0.64) | 3.9 VS 2.8 (HR:0.93, 95%CI = 0.77–1.12, P = 0.44) | 20.1% vs 13.7% (OR:1.61, 95%CI = 1–2.62, P = 0.05) |
| Soria et al. [49] | Phase2 (NCT01750281.) | Selumetinib + docetaxel | Placebo + docetaxel | NSCLC | 212 | 5.7 vs 7.7 vs 11.5 | 3 vs 4.2 vs 4.3 (HR = 1.12,0.92) | 33% vs 14% (OR:3.26, 95%CI = 1.47–7.95) |
| Greystoke et al. [50] | Phase1 (NCT01809210) | Selumetinib + gemcitabine/cisplatin or carboplatin | Selumetinib + pemetrexed/cisplatin or carboplatin | NSCLC | 55 | NA | NA | 36% vs 33% vs 19% vs 13% |
| Seto et al. [51] | Phase1 (NCT01605916) | Selumetinib + docetaxel | Selumetinib | Solid tumor of NSCLC | 25 | NA | NA | NA |
| Melosky et al. [44] | phase2 | Selumetinib + pemetrexed + cisplatin | No selumetinib | Non-squamous NSCLC | 62 | 10 vs 10.1 vs 15.3 (HR = 1.56,1.72)(P = 0.31,0.2) | 7.2 vs 6.9 vs 4 (HR = 0.82,0.77)(P = 0.56,0.44) | 35% vs 62% vs 24% |
NA, non-available; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival, PFS, progression-free survival; HR, hazard ratio