Table 1.
Summary of 4 successful and 16 unsuccessful comparisons explored for addition to the FOCUS4 platform.
| Cohort | Biomarker | BMincidence (%) | Intervention | Outcome |
|---|---|---|---|---|
| A1 | BRAF V600E mutation | 10 | BRAF I and MEKi | Science evolved |
| A2 | BRAF V600E mutation | 10 | Dabrafenib, trametinib+panitumumab | GSK sold oncology portfolioto Novartis. Novartis: insufficient activityto support. |
| B1 | PIK3CA mutant or PTEN loss on IHC | 22 | Dual PI3Ki/mTORi | Insufficient evidence of benefit |
| B2 | PIK3CA mutation | 12 | Aspirin | FOCUS4-B trial |
| C1 | KRAS/NRAS mutation | 45 | MEKi + PI3Ki | Found to be too toxic inearly studies |
| C2 | RAS mutation + HLA A-2 | 20 | IMA 190 peptide vaccine | Company did not commit |
| C3A | H3K36me3 loss | <2 | Wee-1 inhibitor AZD1775 | Biomarker: very low incidenceof loss |
| C3B | RAS + TP53 double mutation | 30 | Wee-1 inhibitor | FOCUS4-C trial |
| C3C | ATM loss | 6 | ATM inhibitor AZD 6738 | Company did not support concept |
| D1 | KRAS, NRAS and BRAF wildtype | 40 | Pan-HER inhibitor AZD8931 | FOCUS4-D trial |
| D2 | KRAS, NRAS and BRAF wildtype | 40 | MM151 | Company sold asset prior tocontract |
| D3 | Triple wildtype, HER2 negative | 25 | Cetuximab + CDK4/6i | Pending data from SCCHN |
| E1 | MMR deficient and POLE mutant | 4 | Avelumab | Company did not support concept |
| E2 | MMR deficient or TGFb activated | 30 | Bintrafusp-alfa | EME/CRUK did not extend grant |
| F | Axin 2 overexpressed | 9 | RXC004 porcupine inhibitor | EME/CRUK did not extend grant |
| G | HER-2 overexpressed | 2 | Trastuzumab + CDK4/6i | Biomarker incidence too low |
| H | ALK/ROS rearrangements | 2 | Crizotinib | Biomarker incidence too low |
| N1 | Non-stratified group | - | Capecitabine | FOCUS4-N trial |
| N2 | Non-stratified group | - | Add TAS-102 | Global company did not support concept |
| N3 | Non-stratified group | - | Metronomic cyclophosphamide | EME/CRUK did not extend grant |