What is small-molecule targeted therapy?
Since the early 21st century, there has been an explosion of breakthrough cancer treatments designed to target specific mutations found in cancer cells. The global market for small-molecule targeted therapies is projected to grow from $77.3 billion in 2025 to $110.5 billion by 2029, driven by precision medicine and genomic integration. In the U.S., targeted small-molecule therapies are expected to reach $80 billion by 2033, reflecting strong adoption in oncology care.
Targeted therapies are a prime example of precision medicine in cancer care, and are often more effective and less toxic than the traditional approach of chemotherapy, which tends to damage both healthy and cancer cells.
However, targeted therapies do not work for every patient diagnosed with cancer. For example, with non-small cell lung cancer (NSCLC), the most prominent form of lung cancer, there are approximately a dozen cancer cell mutations, found in 20% of NSCLC patients, that have at least one corresponding targeted therapy drug treatment. These eligible lung cancer patients would greatly benefit from targeted therapy instead of chemotherapy and/or immunotherapy, which research suggests could lead to suboptimal outcomes. Fortunately, genomic testing for these particular mutations can identify NSCLC patients who are more likely to benefit from targeted therapies. The National Comprehensive Cancer Network (NCCN) now emphasizes comprehensive biomarker testing for all NSCLC patients, regardless of stage or histology. Testing has evolved from single-gene to multi-dimensional biomarker analysis (DNA, RNA, protein), reducing delays and improving precision. Recent FDA approvals, such as sevabertinib for HER2-mutated NSCLC, highlight the importance of upfront testing.
Despite inclusion of genomic testing in NCCN guidelines, low testing adherence had been an ongoing concern. According to a PubMed Central study, more than 50% of NSCLC treatment cases did not have genomic testing performed in accordance with the NCCN guidelines. While real-world adherence improved to 86.3% in 2025, gaps still remain for newly added biomakers.
This could be for a few reasons:
- Some oncologists may not be aware of the testing recommendations, given the challenge of keeping up with the rapid advancements of cancer treatments and updates to treatment guidelines.
- Others may not be willing to wait for the test results, which can take up to two weeks, before starting traditional chemotherapy and immunotherapy treatments, even though many patients with advanced NSCLC are not likely to experience much disease progression during this timeframe.
- Some likely believe that they can simply switch the patient to a targeted therapy if eligible at a later date, but studies indicate that in certain situations, starting immunotherapy before targeted therapy increases toxicity, including liver inflammation and failure. NCCN advises delaying immunotherapy until genomic results are available.
This missed opportunity to test for targeted therapies results in qualified patients receiving less effective treatment, and delaying the most appropriate treatment to a later time, which leads to poorer health outcomes and increased health care costs.
How to increase genomic testing through prior authorization
Evernorth’s Comprehensive Oncology Management helps close the genomic testing gap by leveraging prior authorization protocols to ensure that oncologists submit genomic test results prior to beginning first line therapy for advanced NSCLC. Oncologists who do not submit test results are immediately contacted for a peer-to-peer consultation, where they learn of the NCCN guidelines and the importance of postponing any immunotherapy until the genomic test results are known. If the patient has severe symptoms that need to be addressed urgently, the provider is directed to the NCCN recommendation to consider holding immunotherapy for the first cycle and using a chemotherapy regimen alone. If genomic testing returns negative, immunotherapy can be added with the next cycle of therapy. This approach helps avoid exposing patients with actionable mutations to immunotherapy, reducing the risk of serious toxicity.
Engaging oncologists to conduct genomic testing before beginning treatment enables them to direct cancer patients to the first-line therapy that is most effective for each individual. This helps improve the cancer care experience for patients as they undergo an already challenging treatment journey. It also leads to better health outcomes, which translates to lower downstream health care costs for plan sponsors.
Evernorth’s Comprehensive Oncology Management provides a real-time and dynamic clinical decision support tool to ensure that the most appropriate genomic testing is completed, and results are considered when choosing the NCCN-recommended treatment regimen. Peer to peer consultations with board certified medical oncologists provides additional support to ordering physicians as they make treatment choices.
Originally published on 7/26/2022 and updated on 1/15/2026.
Evernorth Comprehensive Oncology Management program integrates medical and radiation oncology, radiology, genomic laboratory utilization management, and claims payment integrity with our comprehensive oncology solution. Leveraging this collection of solutions supports patients and providers from cancer diagnosis throughout treatment.
