Why test for biomarkers in mNSCLC?
Nearly 1 in 2 patients with mNSCLC may have an actionable mutation that can be treated with a targeted therapy7-15*
PD-L1 IS AN IMMUNE CHECKPOINT PROTEIN, NOT AN ACTIONABLE MUTATION16
- METex14 has a prevalence of ~3%, representing ~4,000-5,000 patients with mNSCLC per year in the United States17,18†
- Patients with METex14 in mNSCLC face a poor prognosis19-21
- 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 intervention22
- 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 test23,24
Single-gene testing for multiple biomarkers sequentially may:
- Result in longer turnaround times and increase the risk of tissue exhaustion, potentially necessitating a rebiopsy25,26
- Fail to identify clinically relevant genomic alterations, narrowing the treatment options for patients27
ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; 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.28
- 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)28‡
Blood-based FoundationOne®Liquid CDx
FoundationOne®Liquid CDx analyzes DNA extracted from plasma.29
- 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-130,§,||
- Negative percentage agreement was 100% (72/72)¶
- Foundation Medicine results have a typical turnaround time of ≤12 days (FoundationOne®CDx) and ≤10 days (FoundationOne®Liquid CDx) from receipt of specimen31,32
- FoundationOne®CDx and FoundationOne®Liquid CDx are covered by Original Medicare and Medicare Advantage for qualifying beneficiaries33
- Foundation Medicine offers in-home blood draw with mobile phlebotomy to support broader access to FoundationOne®Liquid CDx at no additional cost34
Reflex to an FDA-approved tissue test in the event of negative findings on blood-based test results, if feasible2
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.3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed July 11, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. 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. 2. Tabrecta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 3. Data on file. Study CINC280A2201, August 2021. Novartis Pharmaceuticals Corp; 2021. 4. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2019. 5. Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14–mutated or MET-amplified non–small-cell lung cancer. N Engl J Med. 2020;383(10):944-957. 6. Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14–mutated or MET-amplified non–small-cell lung cancer. Supplementary Appendix. N Engl J Med (suppl). doi:10.1056/NEJMoa2002787. 7. Shea M, Costa DB, Rangachari D. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Ther Adv Respir Dis. 2016;10(2):113-129. 8. Awad MM, Oxnard GR, Jackman DM, et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 2016;34(7):721-730. 9. Nadal E, Chen G, Prensner J, et al. KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma. J Thorac Oncol. 2014;9(10):1513-1522. 10. Scheffler M, Ihle MA, Hein R, et al. K-ras mutation subtypes in NSCLC and associated co-occuring mutations in other oncogenic pathways. J Thorac Oncol. 2019;14(4):606-616. 11. Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. 12. Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-229. 13. Brustugun OT, Khattak AM, Trømborg AK, et al. BRAF-mutations in non-small cell lung cancer. Lung Cancer. 2014;84(1):36-38. 14. Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469-1472. 15. D’Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol. 2011;29(15):2066-2070. 16. NCI Dictionary of Cancer Terms. PD-L1. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pd-l1. Accessed July 11, 2022. 17. Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer – a systematic review and meta-analysis. Lung Cancer. 2018;123:76-82. 18. Data on file. Novartis Calculation. Kantar Health. CancerMPact: lung (non-small cell) metastatic stage IV incidence and newly recurrent. Updated December 15, 2018. my.khapps.com. 19. Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T, Ho C. Patterns of spread and prognostic implications of lung cancer metastasis in an era of driver mutations. Curr Oncol. 2017;24(4):228-233. 20. Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer. 2019;133:96-102. 21. Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Supplementary Table 2. Lung Cancer (suppl). doi.org/10.1016/j.lungcan.2019.05.011. 22. Kim EK, Kim KA, Lee CY, et al. Molecular diagnostic assays and clinicopathologic implications of MET exon 14 skipping mutation in non–small-cell lung cancer. Clin Lung Cancer. 2019;20(1):e123-e132. doi:10.1016/j.cllc.2018.10.004. 23. Hinrichs JW, van Blokland WT, Moons MJ, et al. Comparison of next-generation sequencing and mutation-specific platforms in clinical practice. Am J Clin Pathol. 2015;143(4):573-578. 24. Yu TM, Morrison C, Gold EJ, Tradonsky A, Layton AJ. Multiple biomarker testing tissue consumption and completion rates with single-gene tests and investigational use of Oncomine Dx Target Test for advanced non–small-cell lung cancer: a single-center analysis. Clin Lung Cancer. 2019;20(1):20-29. 25. Pennell NA, Mutebi A, Zhou Z-Y. 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. doi:10.1200/PO.18.00356. 26. Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture–based next-generation sequencing identiļ¬es actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res. 2015;21(16):3631-3639. 27. Ali SM, Hensing T, Schrock AB, et al. Comprehensive genomic profiling identifies a subset of crizotinib-responsive ALK-rearranged non-small cell lung cancer not detected by fluorescence in situ hybridization. Oncologist. 2016;21(6):762-770. 28. Foundation Medicine, Inc. FoundationOne®CDx Technical Information. Cambridge, MA: Foundation Medicine, Inc. 29. Foundation Medicine, Inc. FoundationOne®Liquid CDx Technical Information. Cambridge, MA: Foundation Medicine, Inc. 30. Data on file. Study CINC280A2201, Plasma CDx. Novartis Pharmaceuticals Corp; 2021. 31. Foundation Medicine, Inc. What is FoundationOne CDx? https://www.foundationmedicine.com/test/foundationone-cdx. Accessed July 11, 2022. 32. Foundation Medicine, Inc. What is FoundationOne®Liquid CDx? https://www.foundationmedicine.com/test/foundationone-liquid-cdx. Accessed July 11, 2022. 33. Foundation Medicine, Inc. Billing and financial assistance. https://www.foundationmedicine.com/resource/billing-and-financial-assistance. Accessed July 11, 2022. 34. Foundation Medicine, Inc. Foundation Medicine mobile phlebotomy. https://assets.ctfassets.net/w98cd481qyp0/4jVqxTjDfcHxzGmzwyKZCb/ec459c0296895b15101ac1a21e066f94/Mobile_Phlebotomy_Overview_HCP.pdf. Accessed July 11, 2022. 35. 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 drug reaction, temporarily withhold, dose reduce, 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.
