Why comprehensive biomarker testing may be worth the wait5
Selectivity
Outcomes
Safety6,8,9,11
Confirming biomarker status before starting treatment could alter your treatment plan.9
RET+ NSCLC: identifying an underserved patient population
For decades we’ve known RET as an oncogenic driver that promotes uncontrolled cell growth.1 Now, RET is part of a growing list of biomarkers in NSCLC that demand our attention.2-4
RET is a known oncogenic driver in several tumor types.5 RET alterations—in the form of fusions—have been identified in non–small cell lung cancer (NSCLC), and up to 2% of patients with NSCLC have RET+ cancer.5-7
RET+=rearranged during transfection positive.
Not performing a broad molecular profiling test—or initiating treatment prior to receiving results—could lead to a missed opportunity.6,8-11
Test for RET and other biomarkers to potentially impact treatment decisions2
Without comprehensive biomarker testing, patients with metastatic non–small cell lung cancer (mNSCLC) who are candidates for targeted therapy could be missed.9,10 Therapies that don’t target active oncogenic drivers can translate into worse outcomes, including lower overall survival rates.9,10
That’s why testing is critical. To identify rare driver mutations, such as RET, in eligible patients with metastatic NSCLC who may be candidates for targeted therapy, the National Comprehensive Cancer Network® (NCCN®) NSCLC Panel recommends molecular testing for actionable biomarkers, including RET, and strongly advises broad molecular profiling.12
Identifying oncogenic drivers can shape the course of a patient’s treatment plan,5,9,10 but it’s important to acknowledge that there is a waiting period to receive NGS test results—typically about 2 weeks.13,14 With a diagnosis of mNSCLC, patients may feel anxious to receive treatment as soon as possible. However, waiting to receive NGS results to confirm biomarkers whenever possible before initiating treatment can have important and worthwhile benefits.5,9,10 In a clinical trial of patients with ALK+ NSCLC, targeted therapy resulted in a 5-year overall survival rate in 3 out of 5 patients.15
Those few weeks of waiting can mean a difference for your patients: a treatment approach based on targeting specific biomarkers can lead to improved patient outcomes. One study found a median increase in overall survival of about 5 months.9
Patients can see improvements in efficacy, safety, and tolerability when a highly selective targeted therapy is used rather than a less selective therapy like chemotherapy or multikinase inhibitors (MKIs).6,8,11 Patients with RET+ NSCLC and other specific biomarkers may also have poor outcomes with immunotherapy (IO) and are often excluded from IO clinical trials.16,17 In fact, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend patients, across all PD-L1 expression levels, are negative for actionable molecular markers before utilizing IO as a first-line treatment option.12
Use NGS to confirm whether your patient has a biomarker—like RET—and tailor your treatment plan in your pursuit of precision medicine for every patient with NSCLC.5
ALK+=anaplastic lymphoma kinase positive; NGS=next-generation sequencing; PD-L1=programmed death-ligand 1.
What’s your testing approach?
About 1 in 2 patients with mNSCLC have biomarkers with approved, emerging, or evolving therapeutics.2
Emerging Therapeutics=currently being studied in clinical trials; Evolving Therapeutics=either proof-of-concept studies or in a very early stage.
Blueprint Medicines: dedicated to developing targeted therapies for patients with mNSCLC
Blueprint Medicines is a precision therapy company focused on genomically defined cancers, rare diseases, and cancer immunotherapy. As part of our commitment to developing targeted therapies for patients, Blueprint Medicines is continuing to research various biomarkers, including RET, in NSCLC.
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.
References: 1. Takeuchi K. Discovery stories of RET fusions in lung cancer: a mini-review. Front Physiol. 2019;10:216.
2. VanderLaan PA, Rangachari D, Costa DB. The rapidly evolving landscape of biomarker testing in non–small cell lung cancer. Cancer Cytopathol. 2021;129(3):179-181.
3. Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013;18(7):865-875.
4. O’Leary C, Xu W, Pavlakis N, Richard D, O’Byrne K. Rearranged during transfection fusions in non-small cell lung cancer. Cancers (Basel). 2019;11(5):620.
5. Kato S, Subbiah V, Marchlik E, Elkin SK, Carter JL, Kurzrock R. RET aberrations in diverse cancers: next-generation sequencing of 4,871 patients. Clin Cancer Res. 2017;23(8):1988-1997.
6. Drilon A, Hu ZI, Lai GGY, Tan DSW. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167.
7. Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18(3):382-384.
8. Mayekar MK, Bivona TG. Current landscape of targeted therapy in lung cancer. Clin Pharmacol Ther. 2017;102(5):757-764.
9. Barlesi F, Mazieres J, Merlio JP, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016;387(10026):1415-1426.
10. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006.
11. Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA. 2019;322(8):764-774.
12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 18, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.
13. FoundationOne CDx™. Frequently asked questions about the first FDA-approved broad companion diagnostic (CDx) test for solid tumors. https://assets.ctfassets.net/vhribv12lmne/3kpybus0YU64E4uSi8CYYS/7845140a1e74fc7ae71d05769a55f192/F1CDx_FAQs.pdf. Accessed March 24, 2023.
14. Pennell NA, Mutebi A, Zhou ZY, et al. Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non–small-cell lung cancer using a decision analytic model. JCO Precis Oncol.2019;3:1-9.
15. Hotta K, Hida T, Nokihara H, et al. Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer. ESMO Open. 2022;7(4):100527.
16. Sabari JK, Offin MD, Wu SL, et al. RET-rearranged lung cancers: immunophenotype and response to immunotherapy. J Clin Oncol. 2018;36(suppl 15). Abstract 9034.
17. Offin M, Guo R, Wu SL, et al. Immunophenotype and response to immunotherapy of RET-rearranged lung cancers. JCO Precis Oncol.2019;3:PO.18.00386. doi:10.1200/PO.18.00386.