Table 1 |.
Companion diagnostics currently approved by the FDA
| Drug (brand name) | Indication | Biomarker | Technology (year PMA first approved) |
|---|---|---|---|
| Afatinib(Cilotrif) | NSCLC | ECFR exon 19 deletions or exon 21 (L858R) substitution mutations | RT-PCR(2013) |
| Cetuximab (Erbitux) and panitumumab (Vectibix) | Colorectal cancer | KRAS mutation negative or KRAS and NRAS* mutation negative | IHC (2004); RT-PCR (2012); NGS* (2017) |
| Crizotinib (Xalkori) | NSCLC | ALK overexpression or gene fusion | FISH (2011); IHC (2015) |
| Crizotinib(Xalkori) | NSCLC | ROS1 fusions | NGS(2017) |
| Dabrafenib (Tafinlar) and trametinib (Mekinist) | Melanoma | BRAFV600E or BRAFV600K mutations | RT-PCR(2013);NGS (2017) |
| Dabrafenib (Tafinlar) and trametinib (Mekinist) | NSCLC | BRAFV600E or BRAFV600K mutations | NGS(2017) |
| Deferasirox (Exjade) | Non-transfusion-dependent thalassaemia | Liver iron concentration | MRI(2013) |
| Enasidenib(ldhifa) | AML | IDH2 mutation positive | PCR(2017) |
| Erlotinib(Tarceva) | NSCLC | EGFR exon 19 deletions or exon 21 (L858R) substitution mutations | RT-PCR(2013) |
| Cefitinib(lressa) | NSCLC | EGFR exon 19 deletions or exon 21 (L858R) substitution mutations | RT-PCR(2O15);NGS (2017) |
| Imatinib(Cleevec) | Gastrointestinal stromal tumours | KIT expression | IHC (2005) |
| Midostaurin (Rydapt) | AML | FLT3 mutation-positive | PCR(2017) |
| Olaparib (Lynparza) | Ovarian cancer | BRCA1 or BRCA2 mutation | PCR and Sanger sequencing (2014) |
| Osimertinib (Tagrisso) | NSCLC | EGFRT790M mutation | RT-PCR(2016) |
| Pembrolizumab (Keytruda) | NSCLC | PDL1 expression | IHC (2016) |
| Rucaparib (Rubraca) | Ovarian cancer | BRCA1 or BRCA2 mutation | NGS(2016) |
| Trastuzumab (Herceptin) | Breast cancer | HER2 expression and/or ERBB2 amplification | ISH (2011); CISH (2011); IHC (2012) |
| Trastuzumab (Herceptin); pertuzumab (Perjeta) and ado-trastuzumab emtansine (Kadcyla) | Breast cancer, gastric cancer | ERBB2 amplification | FISH (2005); ICC (1998) |
| Vemurafenib (Zelboraf) | Melanoma | BRAfV600E mutations | RT-PCR(2011) |
| Venetoctax (Venclexta) | B cell chronic lymphocytic leukaemia | Deletion of 17p (which contains TP53) | FISH (2016) |
All FDA-cleared or FDA-approved companion diagnostic devices on 14 August 2017, not including humanitarian device exemptions. The FDA describes a companion diagnostic as an “in vitro diagnostic device that provides information that is essential for the safe and efficacious use of the corresponding therapeutic product” (see the FDA website). Thus, the number of approvals of companion diagnostics is a measure of progress in the approval of new precision medicines. Notably, all but two companion diagnostics were approved after 2005, and all but one were developed for oncology indications. AML, acute myelogenous leukaemia; CISH, chromogenic in situ hybridization; EGFR, epidermal growth factor receptor; FISH, fluorescence in situ hybridization; HER2, receptor tyrosine-protein kinase erbB-2; IHC, immunohistochemistry; ISH, in situ hybridization; KIT, mast/stem cell growth factor receptor KIT; MRI, magnetic resonance imaging; NSCLC, non-small-cell lung cancer; NGS, next-generation sequencing; PDL1, programmed cell death 1 ligand 1; PMA, premarket approval application; RT-PCR, real-time PCR.
Panitumumab only.