Table 1.
Summary of phase II or III clinical trials investigating KRAS-related therapy in patients with pancreatic cancer.
| Target gene/pathway | Tested drug | n (subjects) | Treatment setting | Therapeutic scheme | Phase | Median OS | Median PFS | Ref |
|---|---|---|---|---|---|---|---|---|
| KRAS | Tipifarnib | 688 | Untreated advanced PDAC | Gem + tipifarnib vs gem + placebo | III | 193 vs 182 days, P = 0.75 | 112 days vs 109 days, P = 0.72 | [53] |
| Pelareorep | 73 | Untreated metastatic PA | Paclitaxel/carboplatin+ pelareorep vs paclitaxel/carboplatin | II | 7.3 months vs 8.8 months, P = 0.68 | 4.9 months vs 5.2 months, P = 0.6 | [56] | |
| Ras oncogene peptide vaccines | 23 | Resectable PDAC with surgery | Single or seven peptide vaccination | II | 27.5 months | – | [201] | |
| KRAS/RAF/MEK | Pimasertib | 88 | Metastatic PC | Gem + pimasertib vs gem + placebo | II | 7.26 months vs 7.59 months, P = 0.674 | 3.75 months vs 2.83 months, P = 0.681 | [202] |
| Selumetinib, erlotinib | 46 | Previously treated advanced PDAC | Combination of selumetinib and erlotinib | II | 7.3 months (95% CI, 5.2–8.0 months) | 1.9 months (95% CI, 1.4–3.3 months) | [203] | |
| Trametinib | 160 | Metastatic PDAC | Gem + trametinib vs gem + placebo | II | 8.4 months vs 6.7 months, P = 0.453 | 16.1 weeks vs 15.1 weeks, P = 0.349 | [204] | |
| Selumetinib | 70 | Metastatic PC with failed first-line gemcitabine therapy | Selumetinib vs capecitabine | II | 5.4 months vs 5.0 months, P = 0.92 | 2.1 months vs 2.2 months, P = 0.41 | [205] | |
| Refametinib | 80 | Advanced PDAC | Refametinib + gem | II | 8.4 months (95% CI, 6.4–11.6 months) | 5.4 months (95% CI, 4.0–7.1 months) | [206] | |
| CI1040 | 15 | Advanced PC | CI1040 | II | – | – | [207] | |
| Selumetinib, MK-2206 | 120 | Metastatic PC | Selumetinib + mk-2206 vs mFOLFOX | II | 3.9 months vs 6.7 months, P = 0.15 | 1.9 months vs 2.0 months, P = 0.02 | [199] | |
| KRAS/PI3K/AKT/mTOR | Temsirolimus | 55 | Metastatic PC | Gem + temsirolimus | II | 4.95 months (95% CI 3.54–6.85) | 2.69 months (95% CI 1.74–4.95) | [208] |
| Everolimus | 31 | Advanced PC | Capecitabine + everolimus | II | 8.9 months (95% CI 4.6–13.1 months) | 3.6 months (95% CI 1.9–5.3) | [209] | |
| Everolimus, cetuximab | 31 | Locally advanced or metastatic PDAC | Everolimus, cetuximab and capecitabine | II | 5.0 months (CI 3.1–6.8 months) | – | [210] | |
| Everolimus | 33 | Metastatic PDAC with a failure of the 1st gem-based chemotherapy | Everolimus | II | 4.5 months | 1.8 months | [211] | |
| Temsirolimus, everolimus, cetuximab |
A: 5 B: 16 |
Metastatic PDAC |
A: temsirolimus B: everolimus + erlotinib |
II |
A: 44 days B: 87 days |
A: 19 days B: 49 days |
[212] | |
| Rigosertib | 160 | Untreated metastatic PDAC | Rigosertib + gem vs gem | II/III | 6.1 months vs 6.4 months, HR = 1.24 (95% CI 0.85–1.81) | 3.4 months vs 3.4 months, HR = 0.96, 95% CI 0.68–1.36 | [213] | |
| KRAS/RAF/MEK/ERK | Sorafenib | 24 | Untreated locally advanced or metastatic PDAC | Oxaliplatin, capecitabine and sorafenib | II | 8.1 months (95% CI 3.5–10.9) | 6.0 months (95% CI 2.5–9.6) | [214] |
| Sorafenib | 102 | Untreated locally advanced or metastatic PDAC | Gem + sorafenib vs gem + placebo | III | 8 months and 9.2 months, P = 0.231 | 3.8 months and 5.7 months, P = 0.902 | [215] | |
| Sorafenib |
A: 15 B: 37 |
Metastatic PC |
A: sorafenib B: gem + sorafenib |
II |
A: 4.3 months (95% CI: 3.3–8.3) B: 6.5 months (95% CI: 5.5–8) |
A: 2.3 months (95% CI: 1.2–5.7) B: 2.9 months (95% CI: 2.1–4.3) |
[216] | |
| Sorafenib, erlotinib | 38 | Advanced PDAC | sorafenib + erlotinib | II | 99.5 days (95% CI: 71–188) | Eight-week PFS rate of 46% (95% CI: 0.32–0.67) | [217] | |
| EGFR | Erlotinib | 569 | Locally advanced or metastatic PDAC | Gem + erlotinib vs gem + placebo | III | 6.24 months v 5.91 months, P = 0.038 | 3.75 months v 3.55 months, P = 0.004 | [218] |
OS overall survival, PFS progression-free survival, gem gemcitabine, tipifarnib farnesyltransferase inhibitor, pelareorep oncolytic virus, pimasertib MEK1/2 inhibitor, selumetinib MEK1/2 inhibitor, erlotinib EGFR inhibitor, refametinib MEK1/2 inhibitor, trametinib MEK1/2 inhibitor, CI1040 MEK1/2 inhibitor, MK-2206 AKT inhibitor, temsirolimus mTOR inhibitor, everolimus mTOR inhibitor, cetuximab EGFR inhibitor, rigosertib PI3K/PLK1 inhibitor, sorafenib BARF inhibitor.