Table 1.
Trials on MEK 1/2 Inhibitors
| Author, Year | Drug tested | Study design | Population | N | Outcome |
|---|---|---|---|---|---|
| Phase 1 trials | |||||
| Adjei, et al 2011 [26] | Refametinib + sorafenib | Dose escalation | HCC/non-HCC | 62 (4 PDAC) | MTD; DCR†=65.8 % |
| Infante, et al 2012[25] | Trametinib | Dose escalation | Advanced cancer | 206 (26 PDAC) | MTD, RP2D; DCR=50% |
| Bedard, et al 2015[27] | Trametinib + buparlisib | Dose escalation | RAS-/BRAF-mutant advanced cancer | 113 (24 PDAC) | MTD, RP2D; PFS=2 mo; mOS=5 mo |
| Weekes, et al 2017[28] | Cobimetinib + GDC-0994 | Dose escalation | Advanced cancer with limited options | 23 (7 PDAC) | MTD; BOR (SD+PR) = 55% |
| Phase 2 trials | |||||
| Infante, et al 2014[17] | Trametinib + Gem | Placebo controlled multicenter RCT | Untreated metastatic PDAC | 160 | mOS=8.4 Vs 6.7 mo; p= 0.453 |
| Bodoky, et al 2011[20] | Selumetinib Vs Capecitabine | Multicenter RCT | Metastatic PDAC | 70 | mOS=5.4 Vs 5.0 mo; p= 0.92 |
| Van Cutsem, et al 2018[18] | Pimasertib + Gem | Double blind multicenter RCT | Metastatic PDAC | 88 | PFS 3.7 Vs 2.8 mo; p= 0.68 |
| Van Laethem, et al 2016[19] | Refametinib + Gem | Single arm non-randomized trial | Advanced PDAC | 60 | ORR 23% |
| Ko, et al 2016[21] | Selumetinib + Erlotinib | Single arm non-randomized study | Inoperable PDAC | 46 | 24-week OS¶=58% |
| Chung, et al 2017[22] | Selumetinib + MK-2206 | Open-label RCT | Metastatic PDAC (Failed Gem) | 137 | OS: 3.9 Vs 6.7 mo; HR 1.37, p=0.15 |
†
Secondary outcome;
¶
24-week OS rate of at least 43.5% was a pre-specified indicator of “Positive response”.
HCC hepatocellular carcinoma; RCT randomized controlled trial; MTD maximum tolerated dose; DCR disease control rate; RP2D recommended phase 2 dose; PFS progression free survival; mo month; mOS median overall survival; Vs versus; BOR Best overall response; SD stable disease; PR partial response; Gem gemcitabine; ORR objective response rate; HR hazard ratio.