Targeted Therapy in Non-Small Cell Lung Cancer

*Please note: This slide show is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always consult your doctor about any questions you may have regarding a medical condition.

What is targeted therapy?

Targeted therapy is a cancer treatment directed towards specific mutations that drive cancer to grow and spread. Targeted therapies interrupt the growth and function of cancer cells, while avoiding healthy cells. So there can be fewer side effects than with standard chemotherapy.

What is targeted therapy?

You may qualify for targeted therapy based on the results of biomarker testing that looks for all known mutations driving non-small-cell lung cancer (NSCLC). The tests look for specific molecular signs and substances that reveal a cancer's mutations.

What difference can targeted therapy make?

Experts recommend that everyone diagnosed with NSCLC have testing for the presence of driver mutations in the tumor as soon as possible.¹ This testing allows the doctor to prescribe treatment that is tailored to your individual cancer.

Targeted therapy offers hope for people with NSCLC. Many people live longer with targeted therapy.² It may also cause fewer side effects.

Why is biomarker testing so important?

Biomarker testing for Stage I, II, and III

Experts recommend biomarker testing for the driver mutations EGFR, ALK, KRAS, ROS1, cMET, RET, NTRK and BRAF V600E, as well as for levels of the protein, PD-L1, when you are first diagnosed with non-small cell lung cancer.⁴

Biomarker testing in Stage IV and other situations

Doctors also recommend testing for biomarkers if you have Stage IV NSCLC, your cancer spreads or returns after treatment, or you did not have biomarker testing at diagnosis.

Biomarker testing in Stage IV and other situations

Experts are also studying new drugs based on other biomarkers. You may be able to join a clinical trial for a new medicine not yet available to the public.

Why is biomarker testing important for certain groups?

Biomarker testing is important for everyone, including people from certain groups, such as African Americans. In the past, lung cancer rates have been significantly higher in this group.

For example, African American men had higher rates of lung cancer than white men and were much more likely to die of it up until the recent past.³ This is changing, but the death rate and rate of new cancers is still higher in the African American community.

Importance of biomarker testing and targeted therapy for African Americans and other minorities

African Americans tend to be diagnosed at later stages of NSCLC and wait longer for treatment. This and other factors lead to lower survival rates than for white Americans.⁵ This is especially true for African American men. Biomarker testing can help more African Americans receive targeted therapies, which improves survival.

Some other minorities also tend to have higher lung cancer rates and receive less treatment. If you are American Indian, Alaska Native, or a Pacific Islander, be sure to ask your doctor about comprehensive biomarker testing.⁶

Targeted therapy for people with the EGFR mutation

Targeted therapies for specific mutations can be used as the first treatment, or first-line treatment, for NSCLC. They can also be used later as a second treatment, or second-line treatment.

Targeted therapy for the ALK mutation

For the ALK mutation, first-line treatments are alectinib, lorlatinib, or brigatinib.

Ceritinib or any of the drugs not used in first-line treatment are second-line options. It is important to repeat testing for driver mutations if the first-line treatment does not work, because the second-line treatment depends on the cancer's mutation profile at the time that it progresses.

Targeted therapy for the ROS1 mutation

Entrectinib is the preferred first-line treatment for people with a ROS1 mutation, especially if the cancer has spread to the central nervous system.

Targeted therapy for the BRAF mutation

People with a mutation called BRAF V600E can receive a combination of two drugs, dabrafenib and trametinib. This may be a first- and second-line treatment.

Immunotherapy for people with PD-L1

Immunotherapy is used when there are changes in the protein PD-L1. It includes nivolumab,⁷ pembrolizumab,⁸ and atezolizumab. Durvalumab is also an immune therapy drug that is approved for patients with stage 3 NSCLC after receiving chemotherapy and radiation. Immunotherapy allows the immune system to better attack cancer cells.

Immunotherapy for people with PD-L1

These drugs may be a first-line treatment when cancer has metastasized or a second-line treatment if chemotherapy does not work well and certain mutations are present.

Targeted therapy offers hope for NSCLC

If your doctor suspects lung cancer, ask about comprehensive biomarker testing. Experts recommend it for everyone with NSCLC.⁹

If you did not receive it, talk with your doctor about doing the tests now. Targeted therapy can make an important difference in your health outcomes.

References

1. Califf RM. Biomarker definitions and their applications. Exp Biol Med (Maywood). 2018;243(3):213-221. doi:10.1177/1535370217750088
2. Barlesi F, Mazières J, Merlio J-P, et al. Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients. Lancet, Elsevier, 2016, 287 (10026), pp.1415-1426. ⟨10.1016/S0140-6736(16)00004-0⟩. ⟨hal-01259217⟩
3. Centers for Disease Control and Prevention. Leading cancer cases and deaths, all races/ethnicities, male and female, 2017. Available at https://gis.cdc.gov/cancer/uscs/dataviz.html. Accessed February 1, 2021.
4. Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018;142(3):321–346. doi: https://doi.org/10.5858/arpa.2017-0388-CP.
5. American Cancer Society. Cancer facts & figures for African Americans 2019-2021. Atlanta, GA: American Cancer Society, 2019.
6. Ryan BM. Lung cancer health disparities. Carcinogenesis 2018;39(6):741-751. doi: 10.1093/carcin/bgy047. PMID: 29547922; PMCID: PMC5972630.
7. National Cancer Institute. Nivolumab. Available at https://www.cancer.gov/about-cancer/treatment/drugs/nivolumab. Accessed February 2, 2021.
8. National Cancer Institute. Pembrolizumab. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pembrolizumab. Accessed February 2, 2021.
9. Garrido P, Conde E, de Castro J, et al. Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: A National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol. 2020;22(7):989-1003. doi:10.1007/s12094-019-02218-4