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Intracranial responses observed in patients with brain metastases1,2


Intracranial disease control

 

Systemic efficacy in patients with brain metastases at baseline (n=57)*
ORR BY BIRC

56.1%

(95% CI: 42.4, 69.3)

mDOR BY BIRC

9.0 months

(95% CI: 5.6, NE)

DCR

77.2%

(95% CI: 64.2, 87.3)

mPFS

8.5 months

(95% CI: 6.8, 19.4)

mOS

17.5 months

(95% CI: 10.3, 22.3)

Intracranial efficacy in patients with target brain lesions (n=15)
iORR

66.7%

(95% CI: 38.4, 88.2)

iDOR

NE

(0.9, NE)

NCCN

RECOMMENDS


Tepotinib is recommended by the NCCN Guidelines as a systemic therapy option for patients with brain metastases who have a METex14+ skipping alteration in metastatic NSCLC (category 2A)3¶§||

Limitations: For analysis of intracranial activity, brain imaging had no mandatory schedule and, as such, data for this retrospective, ad hoc exploratory analysis were incomplete, and confirmation of response was not required. Impact of prior radiotherapy on this analysis should be considered. Results are subject to change based upon updated analysis. For these reasons, results from these analyses should be interpreted with caution.

*Best overall response per RANO-BM is a composite of radiographic responses, corticosteroid use, and clinical status, giving a more comprehensive overview of the patient compared to RECIST. ORR according to RECIST v1.1 as evaluated by BIRC. Intracranial disease control: defined as CR/PR/SD or non-CR/non-PD. Category 2A definition: based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. §See the NCCN Guidelines for detailed recommendations, including other preferred options. ||The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

BIRC=Blinded Independent Review Committee; CR=complete response; DCR=disease control rate; iDOR=intracranial duration of response; iORR=intracranial overall response rate; mDOR=median duration of response; mOS=median overall survival; mPFS=median progression-free survival; NCCN=National Comprehensive Cancer Network®  (NCCN®); NE=not evaluable; ORR=overall response rate; PD=progressive disease; PR=partial response; RANO-BM=Response Assessment in Neuro-Oncology Brain Metastases; RECIST=Response Evaluation Criteria in Solid Tumors; SD=stable disease.

IMPORTANT SAFETY INFORMATION

TEPMETKO can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ILD/pneumonitis occurred in 2% of patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death.

TEPMETKO can cause hepatotoxicity, which can be fatal. Monitor liver function tests (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], and total bilirubin) prior to the start of TEPMETKO, 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 total bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TEPMETKO. Increased ALT/increased AST occurred in 18% of patients treated with TEPMETKO. Grade 3 or 4 increased ALT/AST occurred in 4.7% of patients. A fatal adverse reaction of hepatic failure occurred in one patient (0.2%). The median time-to-onset of Grade 3 or higher increased ALT/AST was 47 days (range 1 to 262).

TEPMETKO can cause pancreatic toxicity in the form of elevations in amylase and lipase levels. Increased amylase and/or lipase occurred in 13% of patients, with Grade 3 and 4 increases occurring in 5% and 1.2% of patients, respectively. Monitor amylase and lipase levels at baseline and regularly during treatment with TEPMETKO and temporarily withhold, dose reduce, or permanently discontinue based on severity of the adverse event.

TEPMETKO can cause embryo-fetal toxicity. Based on findings in animal studies and its mechanism of action, TEPMETKO 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 or males with female partners of reproductive potential to use effective contraception during treatment with TEPMETKO and for one week after the last dose.

Avoid concomitant use of TEPMETKO with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

Fatal adverse reactions occurred in one patient (0.3%) due to pneumonitis, one patient (0.3%) due to hepatic failure, one patient (0.3%) due to dyspnea from fluid overload, one patient (0.3%) due to pneumonia, one patient (0.3%) due to sepsis, and one patient (0.3%) from unknown cause.

Serious adverse reactions occurred in 51% of patients who received TEPMETKO. Serious adverse reactions in >2% of patients included pleural effusion (6%), pneumonia (6%), edema (5%), general health deterioration (3.8%), dyspnea (3.5%), musculoskeletal pain (2.9%), and pulmonary embolism (2.2%).

The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema (81%), nausea (31%), fatigue (30%), musculoskeletal pain (30%), diarrhea (29%), dyspnea (24%), rash (21%), and decreased appetite (21%).

Clinically relevant adverse reactions in <10% of patients who received TEPMETKO included ILD/pneumonitis, fever, dizziness, pruritus, and headache.

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (81%), increased creatinine (60%), decreased lymphocytes (57%), increased alkaline phosphatase (ALP) (52%), increased ALT (50%), increased AST (40%), decreased sodium (36%), decreased hemoglobin (31%), increased gamma-glutamyltransferase (GGT) (29%), increased potassium (26%), increased amylase (25%), decreased leukocytes (25%), decreased platelets (24%), and increased lipase (21%).

The most common Grade 3-4 laboratory abnormalities (≥2%) in descending order were: decreased lymphocytes (15%), decreased albumin (9%), decreased sodium (9%), increased GGT (6%), increased amylase (5%), increased lipase (5%), increased ALT (4.9%), increased AST (3.6%), and decreased hemoglobin (3.6%).

INDICATION

TEPMETKO is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Please see the full Prescribing Information for TEPMETKO.

 

References: 1. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14–skipping non–small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;9(9):1260-1266. doi:10.1001/jamaoncol.2023.1962 2. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14–skipping non–small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;9(9)(suppl 2):1-15. doi:10.1001/jamaoncol.2023.1962 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2023 © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed February 27, 2024. To view the most recent and complete version of the guidelines, 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.