Precision oncology helps Available targeted medicines—solid tumors Biomarker development is accelerating Targeted therapies may improve to improve patient outcomes Over the last 20 years the development of targeted therapies has accelerated, and a large number of such While it took almost 20 years for the first biomarkers to become targets of oncology precision treatments are currently available. Testing for relevant, actionable biomarkers to identify genetic alterations has medicines and to be routinely analyzed, there are many new candidates in late-stage clinical Non-small cell lung cancer (NSCLC) patients who have received biomarker‐driven therapy as the become a necessary and routine part of the oncology patient management process. trials, and we can expect the spectrum to grow rapidly. oncology patient outcomes first line have had even better survival.

Adapted from John A et al. Oncologist. 2020 Nov; 25(11):e1743–e1752. 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 2017 2018 2019 2020

Precision medicine is enabled by molecular profiling HER2 trastuzumab lapatinib pertuzumab ado-trastuzumab trastuzumab-pkrb fam-trastuzumab deruxtecan-nxki Today, drugs can be selected to directly target the biological pathways causing the disease, while HER2 KRAS ALK BRCA PIK3CA MET IDH1 MEK avoiding suboptimal therapies. Using patient-specific tumor molecular profiling, treatment plans can be Median overall survival emtansine trastuzumab and hyaluronidase-oysk uniquely tailored to help provide the best potential outcome. (Overall survival) EGFR gefitinib cetuximab erlotinib panitumumab erlotinib afatinib necitumumab afatinib atezolizumab (as maintenance therapy) osimertinib osimertinib dacomitinib ALK ROS1 1998 2019/2020 2022 Traditional therapies Precision medicine 1.0 crizotinib ceritinib entrectinib lorlatinib alectinib PF-0646392 21 years On the near horizon BRAF 0.8 vemurafenib dabrafenib brigatinib encorafenib binimetinib MEK EGFR EGFR BRAF ROS1 NTRK FGFR RET exon 20 cMET With CDx trametinib cobimetinib selumetinib 0.6 Without CDx encorafenib Molecular BRCA HRD profile olaparib veliparib niraparib niraparib 0.4 rucaparib talazoparib NTRK larotrectinib Survival probability 0.2 PIK3CA Response to therapy is unpredictable, alpelisib and might expose patients to 0.0 73% of medicines in oncology unnecessary side eects. FGFR 0 20 40 60 80 73% erdafitinib pemigatinib pipelines have associated biomarkers Survival time (months) RET Each patient is given an individualized selpercatinib treatment, specifically addressing an underlying genomic alteration. MET capmatinib

Gene translocations and fusions (e.g., NTRK3) Gene copy number variations (CNVs) (e.g., HER2) Insertions and deletions (indels) (e.g., EGFR exon 19) Single-nucleotide polymorphisms (SNPs) (e.g., BRAF V600E)

Native Insertion Deletion Before translocation After translocation AT AT AT Chromosome 15 Chromosome 15 Native C G C G C G Chromosome 12 Chromosome 12

C G G C

G C G C A T GC C G ETV6 C G C G C G G C A T SNP Normal NTRK3 and NTRK3 and ETV6 NTRK3-ETV6 Amplification Native G C A T ETV6 genes genes with breaks gene fusion A T C G T A G C G C

T A A T GC Deletion G C T A NTRK3 GC

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