Table 2.
Selected Co-Alterations That Accompany MDM2 Amplification and Potential Targeted Therapies
| Co-Alteration | No. of. Patients |
% | Examples of Potential Targeted Therapies* |
|---|---|---|---|
| Tyrosine kinase–associated genes† | 1,385 | 37.9 | |
| EGFR | 462 | 12.7 | Afatinib and erlotinib |
| ERBB2 | 200 | 5.5 | Afatinib and lapatinib |
| ERBB3 | 262 | 7.2 | Afatinib |
| ERBB4 | 17 | 0.5 | Afatinib |
| FGFR1 | 274 | 7.5 | Lenvatinib |
| FGFR2 | 42 | 1.2 | Lenvatinib |
| FGFR3 | 110 | 3.0 | Lenvatinib |
| FGFR4 | 23 | 0.6 | Lenvatinib |
| JAK1 | 3 | 0.1 | Ruxolitinib |
| JAK2 | 44 | 1.2 | Ruxolitinib |
| JAK3 | 6 | 0.2 | Tofacitinib |
| KIT | 94 | 2.6 | Dasatinib, imatinib, or sunitinib |
| PDGFRA | 105 | 2.9 | Dasatinib, imatinib, or sunitinib |
| PDGFRB | 9 | 0.2 | Dasatinib, imatinib, or sunitinib |
| RET | 62 | 1.7 | Cabozantinib, lenvatinib, and vandetanib |
| MAPK signaling–associated genes† | 863 | 23.6 | |
| ARAF | 12 | 0.3 | Sorafenib |
| BRAF | 75 | 2.1 | Dabrafenib, vemurafenib, trametinib, and cobimetinib |
| HRAS | 11 | 0.3 | Trametinib and cobimetinib |
| KRAS | 431 | 11.8 | Trametinib and cobimetinib |
| NRAS | 39 | 1.1 | Trametinib and cobimetinib |
| NF1 | 128 | 3.5 | Trametinib and cobimetinib |
| GNAS | 220 | 6.0 | Trametinib and cobimetinib |
| MAP2K1 | 12 | 0.3 | Trametinib and cobimetinib |
| MAP2K2 | 15 | 0.4 | Trametinib and cobimetinib |
| MAPK1 | 2 | 0.1 | ERK inhibitor in clinical development |
| PTPN11 | 12 | 0.3 | Trametinib and cobimetinib |
| PI3K signaling–associated genes† | 926 | 25.4 | |
| PIK3CA | 392 | 10.7 | Everolimus and temsirolimus |
| PTEN | 268 | 7.3 | Everolimus and temsirolimus |
| AKT1 | 38 | 1.0 | Everolimus and temsirolimus |
| AKT2 | 65 | 1.8 | Everolimus and temsirolimus |
| AKT3 | 26 | 0.7 | Everolimus and temsirolimus |
| STK11 | 151 | 4.1 | Everolimus and temsirolimus |
| TSC1 | 45 | 1.2 | Everolimus and temsirolimus |
| TSC2 | 24 | 0.7 | Everolimus and temsirolimus |
| Cell cycle–associated genes† | 2,502 | 68.5 | |
| CDKN2A | 665 | 18.2 | Palbociclib, ribociclib, and abemaciclib |
| CDKN2B | 454 | 12.4 | Palbociclib, ribociclib, and abemaciclib |
| CCND1 | 457 | 12.5 | Palbociclib, ribociclib, and abemaciclib |
| CCND2 | 145 | 4.0 | Palbociclib, ribociclib, and abemaciclib |
| CCND3 | 90 | 2.5 | Palbociclib, ribociclib, and abemaciclib |
| CDK4 | 1,591 | 43.6 | Palbociclib, ribociclib, and abemaciclib |
| CDK6 | 89 | 2.4 | Palbociclib, ribociclib, and abemaciclib |
| CCNE1 | 128 | 3.5 | Bortezomib |
| TP53-associated genes† | 910 | 24.9 | |
| TP53 | 733 | 20.1 | Anti-VEGF, such as bevacizumab and pazopanib13–16 or WEE1 inhibitors |
| ATM | 154 | 4.2 | Olaparib and ATM inhibitors in development (M6620, M4344, or AZD6738) |
| MDM4 | 49 | 1.3 | No targeted agents available |
| Mismatch repair genes and PD-L1 amplification† |
79 | 2.2 | |
| CD274 (PD-L1) | 33 | 0.9 | Pembrolizumab and nivolumab |
| MLH1 | 10 | 0.3 | Pembrolizumab and nivolumab |
| MSH2 | 11 | 0.3 | Pembrolizumab and nivolumab |
| MSH6 | 20 | 0.5 | Pembrolizumab and nivolumab |
| PMS2 | 8 | 0.2 | Pembrolizumab and nivolumab |
NOTE. n = 3,650 patients.
Abbreviation: VEGF, vascular endothelial growth factor.
*
See the Data Supplement for the rationale for potential targeted therapies.
†
Some patients had more than one co-alteration, therefore subgroup totals will be greater than the total number of patients listed.