Steps to Take After a RET-Positive Lung Cancer Diagnosis

Understanding Your RET Diagnosis

What is RET-Positive Lung Cancer?

RET-positive non-small cell lung cancer (NSCLC) is caused by an abnormal re-arrangement or fusion of the RET gene with other fusion gene partners leading to constitutive activation of the RET kinase which produces uncontrolled cell growth and cancer. This alteration basically results in the RET molecule “on-off” switch to get stuck in the “on” position and causing tumor growth (1). RET fusion NSCLC seem to be more prevalent in younger patients who have never or rarely smoked (2-4).

The only way to detect cancer drivers like RET is to perform comprehensive cancer biomarker testing by sending a tissue sample from a tumor biopsy, or by sending a blood sample for a liquid biopsy test to a laboratory, to check for specific genetic alterations. If the test result is positive for a RET mutation or abnormal rearrangement of the RET gene, this information can help to identify effective treatment and clinical trial options.

Stay Informed

Learn about your cancer type, diagnosis and treatment options. Do not be afraid to ask questions to your doctor or medical care team. Being knowledgeable about your cancer and speaking up about things that are important to you is key to receiving the best care. Reach out to other patients, advocates (sometimes family members of patients), or support groups to connect with others in the RET-positive lung cancer community.

The American Cancer Society Personal Health Manager can help cancer patients keep track of all the information about their diagnosis and treatment. The application can help to answer questions about cancer types and treatments; manage and track medications and side effects; track appointments, test results, and questions for the doctor; and more.

Share your cancer experience with others: The American Cancer Society offers the Cancer Survivors Network (CSN), a tool to connect with others who share similar interests and experiences. Also, CaringBridge helps patients share their personal journey and health updates with loved ones.

What to do After Cancer Diagnosis?

Finding the Right Oncologist for your Cancer Treatment

Finding the right oncologist and medical care team can be one of the most important decisions in the cancer journey. For RET lung cancer, it is critical that the lung oncologist that you choose is aware of the latest research treatment options and is able to work with you through your new cancer diagnosis and treatment.

To find an oncologist, ask the doctor who found your cancer to suggest an oncologist with expertise in RET cancers. You can look for an oncologist in one of the NCI-designated cancer centers that deliver the latest cancer treatments to patients in communities across the United States. It may be better to select an oncologist from these NCI centers who has experience treating patients with RET lung cancer. Your primary care doctor should be able to provide a referral.

Some oncologists who are recognized RET experts:

• Dr. John Heymach at MD Anderson Cancer Center
• Dr. Justin Gainor at Massachusetts General Hospital
• Dr. Alex Drilon at Sloan Kettering Cancer Center
• Dr. Marc Ladanyi at Memorial Sloan Kettering Cancer Center
• Dr. Jessica Lin at Massachusetts General Hospital
• Dr. David Carbone at James Thoracic Oncology Center
• Dr. Vivek Subbiah at Sarah Cannon Research Institute
• Dr. Tejas Patil at UCHealth Lung Cancer Clinic – Anschutz Medical Campus
• More information about some of the RET lung cancer experts

Seek Treatment: Understanding Your RET Treatment Options

Targeted Therapy

First-line treatment for RET-Positive stage IV lung cancer patients are targeted therapies including the FDA-approved selective RET inhibitors that specifically target or inhibit the RET molecule: selpercatinib (Retevmo) and pralsetinib (Gavreto). These RET inhibitors specifically target the RET fusion protein and showed great benefit in RET fusion positive non-small cell lung cancer patients and a high intracranial response rate in RET patients with brain metastases (5-7). The difference between selective RET inhibitors and older RET multi-kinase inhibitors, is that the new compounds are able to target only RET and not other molecules, being more effective and reducing the likelihood of side effects. Specific RET inhibitors showed enhanced tolerability and they are the preferred therapeutic option when compared with other cancer therapies such as multikinase inhibitors, chemotherapy, or immunotherapies based on immune checkpoint inhibitors. Learn more about current RET lung cancer treatment options.

Other Treatment Options

Chemotherapy

Chemotherapy drugs are used for the treatment of NSCLC with the most common combination being the platinum-doublet chemotherapy (a combination of platinum compounds such as carboplatin or cisplatin, and a second chemotherapy agent as pemetrexed, etoposide, gemcitabine, paclitaxel, docetaxel, or vinorelbine). Chemotherapy is a common treatment for NSCLC but as mentioned before, the treatment of stage IV RET lung cancer patients with specific RET inhibitors is encouraged. For early-stage RET NSCLC, chemotherapy after surgery (adjuvant chemotherapy) can help to lower the risk of the cancer coming back. Find more information about chemotherapy as a RET cancer treatment.

Immunotherapy

Immunotherapy is a treatment that uses a person’s immune system to destroy cancer cells. Checkpoint blockade inhibitors that act by taking off the ‘brakes’ of immune cells allowing them to effectively attack and destroy cancer cells, have shown great responses in NSCLC patients. But unfortunately, they have shown limited activity of these agents in RET lung cancer patients. Other therapeutic strategies should be considered before administering immunotherapy alone for the cancer treatment of patients with RET alterations. Find more information about immunotherapy.

Managing Side Effects

Treatment associated side effects are very common. Your doctor will discuss with you any side effects that the treatment may cause before starting the cancer treatment. Talk to your doctor or medical care team as soon as you have side effects to better manage your care. The American lung Association and American Cancer Society offer some resources to learn about common lung cancer side effects.

Getting a Second Opinion

Besides your doctor and your cancer care team, you may want to find another medical oncologist to discuss your cancer diagnosis and treatments. For rare cancers, you may want to ask for a second opinion, which can help you to have more information about your case or answer other questions that you may have. Talk with your doctor if you are considering getting a second opinion, and remember that it is very common for cancer patients to get a second opinion. Learn more about getting a 2nd opinion for your RET cancer.

Joining a Clinical Trial

Clinical trials are monitored scientific research studies that test new treatments or medical approaches in patients. Clinical trials allow you to access potential new cancer treatment options, specially when there are not any FDA-approved treatments available. For RET patients who progressed on RET targeted therapies, joining a clinical trial may allow these patients to have access to other treatments. Talk with your doctor and medical care team about the possibility of joining a RET lung cancer clinical trial. Find potential RET clinical trials using our clinical trials matching tool.

The Importance of Emotional Support for Newly Diagnosed Cancer Patients

The experience of being diagnosed with cancer can be intensely hard and stressful, and an emotional support system is important for most cancer patients during their cancer care journey. Being diagnosed with cancer and going through the diagnosis and treatment may cause a range of strong emotions. You can reach out to a family member and find emotional support resources through Cancer Research UK and the National Cancer Institute. The National Cancer Institute also offers information about emotional support for young people with cancer.

Managing Your Health and Well-being

Cancer patients often search for diet choices, physical activity, and dietary supplements that could improve their quality of life or survival during a serious illness. It is important that the information is based on scientific facts from multiple research studies. Also, it is critical that you talk with your doctor or your health care team when making any changes to diet or lifestyle. The American Cancer Society offers tips about nutrition and physical activity and general cancer care.

References and Resources

1. Drilon A. et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol 15, 151–167 (2018).
2. Lin C, Wang S, Xie W, Chang J, Gan Y. The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis. Cancer Biol Ther 2015;16:1019-28.
3. Qiu Z, Ye B, Wang K, et al. Unique Genetic Characteristics and Clinical Prognosis of Female Patients with Lung Cancer Harboring RET Fusion Gene. Sci Rep 2020;10:10387.
4. Hess, L.M., et al., Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States. BMC Cancer, 2021. 21(1): p. 28.
5. Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2020;383(9):813-824. doi:10.1056/NEJMoa2005653
6. Subbiah V, Gainor JF, Oxnard GR, et al. Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial. Clin Cancer Res. 2021;27(15):4160-4167. doi:10.1158/1078-0432.CCR-21-0800.
7. Gainor JF, Curigliano G, Kim DW, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study [published correction appears in Lancet Oncol. 2021 Aug;22(8):e347]. Lancet Oncol. 2021;22(7):959-969. doi:10.1016/S1470-2045(21)00247-3
8. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/living-with-lung-cancer/what-to-expect
9. https://www.cancer.gov/about-cancer/managing-care/finding-cancer-care
10. https://www.cancer.org/cancer/managing-cancer/finding-care/seeking-a-second-opinion.html

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