Nearly half (43%) of the 198 cancer drugs approved by the FDA between 1998 and 2022 rely on molecular biomarker tests to identify patients. The rate of these precision oncology (PO) approvals accelerated sharply after 2017, from an average of one a year from 1998-2017 to an average of eight a year from 2017-2022.1 Regulators are approving PO products, including gene and chimeric antigen receptor (CAR) T-cell therapies, at ever-earlier stages of development to get them to patients faster. For example, first-in-human Phase 1 cancer trials, which in the 1980s yielded a five percent overall response rate, today produce 15-30% response rates, with even higher rates for biomarker-targeted agents.2
Unfortunately, expedited clinical development and regulatory approval have not necessarily translated into expedited utilization of PO for patients. Health Technology Assessment (HTA) agencies, payers (national governments and private insurers), and prescribers still want a precise evidence-based profile of a new product's benefits and risks.
However, the development routes for PO therapies typically leave significant gaps in the scientific evidence that can delay reimbursement and market access. Pharmaceutical sponsors often utilize expedited regulatory pathways, resulting in less comprehensive comparative safety and efficacy data. Pivotal efficacy trials are frequently single-arm and open-label for ethical and practical reasons.3 They may use surrogate endpoints, including biomarkers of response, such as changes in circulating DNA (ctDNA) levels, rather than traditional clinical outcomes.
The explosion of molecular targets has fragmented once-large diagnostic categories, such as non-small cell lung cancer (NSCLC), into ever smaller subgroups defined by the presence or absence of actionable biomarkers such as PD-1, EGFR, ALK, BRAF, KRAS, and NTRK. As a result, randomized clinical trials (RCTs) have become less feasible and relevant.4 Real-world evidence (RWE)—derived from high-quality, real-world data (RWD)—has become an increasingly important means for developers, regulators, and payers to confirm efficacy and safety.
