Why test for biomarkers in mNSCLC?
~1 in 2 patients with mNSCLC may have an actionable mutation that can be treated with a targeted therapy7-16*
PD-L1 IS AN IMMUNE CHECKPOINT PROTEIN, NOT AN ACTIONABLE MUTATION17
- METex14 has a prevalence of ~3%, representing ~4,000-5,000 patients with mNSCLC per year in the United States18,19†
- Patients with METex14 in mNSCLC face a poor prognosis20-22
- Many of these patients may have bone, liver, and brain metastases, which are associated with poor outcomes
Capmatinib (TABRECTA® tablets) is an NCCN Guidelines® CATEGORY 2A (PREFERRED) FIRST-LINE TREATMENT option for patients with METex14-positive mNSCLC1‡
When to test
To inform up-front treatment planning, test every patient with mNSCLC at diagnosis
According to the NCCN Guidelines for NSCLC, clinicians should obtain biomarker test results in appropriate patients at diagnosis of mNSCLC, prior to administering a first-line therapy, if feasible.1
- Accurate detection of mutations leading to METex14 in mNSCLC could facilitate timely intervention23
- Identifying METex14 in mNSCLC may unlock the option for first-line targeted therapy with TABRECTA2
How to test
Comprehensive genomic profiling may identify a wide range of actionable mutations with 1 test24,25
Single-gene testing for multiple biomarkers sequentially may:
- Result in longer turnaround times and increase the risk of tissue exhaustion, potentially necessitating a rebiopsy26,27
- Fail to identify clinically relevant genomic alterations, narrowing the treatment options for patients28
ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; ERBB2, v-erb-b2 avian erythroblastic oncogene homolog 2; HER2, human epidermal growth factor receptor 2; KRAS, Kirsten rat sarcoma; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping; mNSCLC, metastatic non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase;
RET, rearranged during transfection; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application.
*Prevalence rates are in accordance with those from The Cancer Genome Atlas (TCGA) Research Network, a joint effort between the National Cancer Institute and the National Human Genome Research Institute. To access the latest TCGA data, please visit: cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.
†This calculation is based on a 3% prevalence rate and mNSCLC-specific incidence and recurrence data from Kantar Health.
‡See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other options.
§The NCCN Guidelines for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.
FoundationOne®CDx and FoundationOne®Liquid CDx are the FDA-approved companion diagnostics for TABRECTA® (capmatinib) tablets
Tissue-based FoundationOne®CDx
FoundationOne®CDx analyzes DNA isolated from FFPE tumor tissue specimens.29
- In a retrospective analysis, FoundationOne®CDx demonstrated a 99% positive percentage agreement (n=72/73) with the RNA-based RT-PCR clinical trial assay (CTA) that confirmed METex14 in patients taking TABRECTA® (capmatinib) tablets in GEOMETRY mono-12,*,†
- Negative percentage agreement was 100% (125/125)29‡
Blood-based FoundationOne®Liquid CDx
FoundationOne®Liquid CDx analyzes DNA extracted from plasma.30
- In a retrospective analysis, FoundationOne®Liquid CDx demonstrated a 71% positive percentage agreement (n=55/78) with the CTA that confirmed METex14 in patients taking TABRECTA® (capmatinib) tablets in GEOMETRY mono-131,§,||
- Negative percentage agreement was 100% (72/72)¶
- Foundation Medicine results have a typical turnaround time of 8.8 days (FoundationOne®CDx) and 7.8 days (FoundationOne®Liquid CDx) from receipt of specimen32,33
- FoundationOne®CDx and FoundationOne®Liquid CDx are covered by Original Medicare and Medicare Advantage for qualifying beneficiaries34
- Foundation Medicine offers in-home blood draw with mobile phlebotomy to support broader access to FoundationOne®Liquid CDx at no additional cost35
Reflex to an FDA-approved tissue test in the event of negative findings on blood-based test results, if feasible2
FoundationOne®CDx and FoundationOne®Liquid CDx are qualitative next-generation sequencing based in vitro diagnostic tests for advanced cancer patients with solid tumors and are for prescription use only. FoundationOne CDx utilizes FFPE tissue and analyzes 324 genes as well as genomic signatures. FoundationOne Liquid CDx analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes. The tests are companion diagnostics to identify patients who may benefit from treatment with specific therapies in accordance with the therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the tests does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy for testing with FoundationOne CDx when archival tissue is not available which may pose a risk. When considering eligibility for certain therapies for which FoundationOne Liquid CDx is a companion diagnostic, testing of plasma is only appropriate where tumor tissue is not available. Patients who are tested with FoundationOne Liquid CDx and are negative for other companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible.
For the complete label, including companion diagnostic indications and important risk information, please visit www.F1CDxLabel.com and www.F1LCDxLabel.com.
Clinical Utility Data
References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.2.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed March 28, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. Tabrecta. Prescribing information. Novartis Pharmaceuticals Corp. 3. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2021. 4. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2019. 5. Wolf J, Seto T, Han J-Y, et al. N Engl J Med. 2020;383(10):944-957. 6. Wolf J, Seto T, Han J-Y, et al. N Engl J Med (suppl). doi:10.1056/NEJMoa2002787 7. Shea M, Costa DB, Rangachari D. Ther Adv Respir Dis. 2016;10(2):113-129. 8. Awad MM, Oxnard GR, Jackman DM, et al. J Clin Oncol. 2016;34(7):721-730. 9. Nadal E, Chen G, Prensner J, et al. J Thorac Oncol. 2014;9(10):1513-1522. 10. Scheffler M, Ihle MA, Hein R, et al. J Thorac Oncol. 2019;14(4):606-616. 11. Oxnard GR, Lo PC, Nishino M, et al. J Thorac Oncol. 2013;8(2):179-184. 12. Arcila ME, Nafa K, Chaft JE, et al. Mol Cancer Ther. 2013;12(2):220-229. 13. Brustugun OT, Khattak AM, Trømborg AK, et al. Lung Cancer. 2014;84(1):36-38. 14. Vaishnavi A, Capelletti M, Le AT, et al. Nat Med. 2013;19(11):1469-1472. 15. D’Angelo SP, Pietanza MC, Johnson ML, et al. J Clin Oncol. 2011;29(15):2066-2070. 16. Pillai RN, Behera M, Berry LD, et al. Cancer. 2017;123(21):4099-4105. 17. NCI Dictionary of Cancer Terms. PD-L1. Accessed March 28, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pd-l1 18. Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Lung Cancer. 2018;123:76-82. 19. Data on file. Novartis Calculation. Kantar Health. Updated December 15, 2018. My.khapps.com 20. Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T, Ho C. Curr Oncol. 2017;24(4):228-233. 21. Awad MM, Leonardi GC, Kravets S, et al. Lung Cancer. 2019;133:96-102. 22. Awad MM, Leonardi GC, Kravets S, et al. Lung Cancer (suppl). doi.org/10.1016/j.lungcan.2019.05.011 23. Kim EK, Kim KA, Lee CY, et al. Clin Lung Cancer. 2019;20(1):e123-e132. 24. Hinrichs JW, van Blokland WT, Moons MJ, et al. Am J Clin Pathol. 2015;143(4):573-578. 25. Yu TM, Morrison C, Gold EJ, Tradonsky A, Layton AJ. Clin Lung Cancer. 2019;20(1):20-29. 26. Pennell NA, Mutebi A, Zhou Z-Y. JCO Precis Oncol. 2019. 27. Drilon A, Wang L, Arcila ME, et al. Clin Cancer Res. 2015;21(16):3631-3639. 28. Ali SM, Hensing T, Schrock AB, et al. Oncologist. 2016;21(6):762-770. 29. Foundation Medicine, Inc. FoundationOne®CDx technical information. Accessed March 28, 2023. https://assets.ctfassets.net/w98cd481qyp0/41rJj28gFwtxCwHQxopaEb/70c6c95b4edfe8c18c27c2e2461e5c28/FoundationOne_CDx_Label_Technical_Info.pdf 30. Foundation Medicine, Inc. FoundationOne®Liquid CDx technical information. Accessed March 28, 2023. https://assets.ctfassets.net/w98cd481qyp0/3a8jFw3KUjIU3RWPdcT9Ax/52303a23af6cfbb7a899c90fcb4c22df/FoundationOne_Liquid_CDx_Label_Technical_Info.pdf 31. Data on file. Study CINC280A2201, Plasma CDx. Novartis Pharmaceuticals Corp; 2021. 32. Foundation Medicine, Inc. What is FoundationOne CDx? Accessed March 28, 2023. https://www.foundationmedicine.com/test/foundationone-cdx 33. Foundation Medicine, Inc. What is FoundationOne®Liquid CDx? Accessed March 28, 2023. https://www.foundationmedicine.com/test/foundationone-liquid-cdx 34. Foundation Medicine, Inc. Billing and financial assistance. Accessed March 28, 2023. https://www.foundationmedicine.com/resource/billing-and-financial-assistance 35. Foundation Medicine, Inc. Foundation Medicine mobile phlebotomy. Accessed March 28, 2023. https://assets.ctfassets.net/w98cd481qyp0/4jVqxTjDfcHxzGmzwyKZCb/ec459c0296895b15101ac1a21e066f94/Mobile_Phlebotomy_Overview_HCP.pdf 36. Data on file. Study CINC280A2201, Statistical Analysis Results - Efficacy Analysis on F1LCDx Positive Patients for ASCO2021. Novartis Pharmaceuticals Corp; 2021.
INDICATION
TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
Interstitial Lung Disease (ILD)/Pneumonitis. ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA. ILD/pneumonitis occurred in 4.8% of patients treated with TABRECTA in the GEOMETRY mono-1 study, with 1.9% of patients experiencing grade 3 ILD/pneumonitis and 1 patient experiencing death (0.3%). Nine patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis.
Indication
TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
Interstitial Lung Disease (ILD)/Pneumonitis. ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA. ILD/pneumonitis occurred in 4.8% of patients treated with TABRECTA in the GEOMETRY mono-1 study, with 1.9% of patients experiencing grade 3 ILD/pneumonitis and 1 patient experiencing death (0.3%). Nine patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis.
Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TABRECTA in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/ pneumonitis are identified.
Hepatotoxicity. Hepatotoxicity occurred in patients treated with TABRECTA. Increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) occurred in 15% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased ALT/AST occurred in 7% of patients. Three patients (0.8%) discontinued TABRECTA due to increased ALT/AST.
Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TABRECTA, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, reduce dose, or permanently discontinue TABRECTA.
Pancreatic Toxicity. Elevations in amylase and lipase levels have occurred in patients treated with TABRECTA. Increased amylase/lipase occurred in 14% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased amylase/lipase occurred in 7% and 1.9% of patients, respectively. Three patients (0.8%) discontinued TABRECTA due to increased amylase/lipase. Pancreatitis (grade 3) occurred in 1 patient (0.3%); TABRECTA was permanently discontinued for this event.
Monitor amylase and lipase at baseline and regularly during treatment with TABRECTA. Based on the severity of the adverse reaction, temporarily withhold, dose reduce, or permanently discontinue TABRECTA.
Hypersensitivity Reactions. Serious hypersensitivity reactions occurred in patients treated with TABRECTA in clinical trials other than GEOMETRY mono-1. Signs and symptoms of hypersensitivity included pyrexia, chills, pruritus, rash, decreased blood pressure, nausea, and vomiting. Based on the severity of the adverse reaction, temporarily withhold or permanently discontinue TABRECTA.
Risk of Photosensitivity. Based on findings from animal studies, there is a potential risk of photosensitivity reactions with TABRECTA. In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure, such as use of sunscreen or protective clothing, during treatment with TABRECTA. Advise patients to limit direct ultraviolet exposure during treatment with TABRECTA.
Embryo-Fetal Toxicity. Based on findings from animal studies and its mechanism of action, TABRECTA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose.
Most Common Adverse Reactions. The most common adverse reactions (≥20%) were edema (59%), nausea (46%), musculoskeletal pain (40%), fatigue (34%), vomiting (28%), dyspnea (25%), cough (21%), and decreased appetite (21%). The most common grade 3 adverse reactions (≥2%) were edema (13%), fatigue (8%), dyspnea (7%), pneumonia (6%), musculoskeletal pain (4.3%), nausea (2.4%), and vomiting (2.4%). Grade 4 dyspnea and pneumonia were reported in 0.5% of patients.
Clinically Relevant Adverse Reactions. Clinically relevant adverse reactions observed in <10% of patients were pruritus (including allergic pruritus), ILD/pneumonitis, cellulitis, acute kidney injury (including renal failure), urticaria, and acute pancreatitis.
Laboratory Abnormalities. Select laboratory abnormalities (≥20%) worsening from baseline in patients who received TABRECTA were decreased albumin (72%), increased creatinine (65%), decreased lymphocytes (45%), increased ALT (39%), increased amylase (34%), increased alkaline phosphatase (32%), increased gamma-glutamyltransferase (30%), increased lipase (29%), increased AST (28%), decreased phosphate (26%), decreased leukocytes (25%), increased potassium (25%), decreased hemoglobin (24%), decreased sodium (24%), and decreased glucose (23%).
Please see full Prescribing Information for TABRECTA.
