The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Emibetuzumab
3.2. Onartuzumab
3.3. Tivantinib
3.4. Cabozantinib
3.5. Crizotinib
3.6. Capmatinib
4. Discussion
5. Conclusions
Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
NSCLC | Non-small cell lung cancer |
RTK | Receptor tyrosine kinase |
RAS | Rat sarcoma virus |
RAF | Serine/threonine-protein kinase |
KRAS | Kirsten rat sarcoma |
EGFR | Epidermal growth factor receptor |
BRAF | v-Raf murine sarcoma viral oncogene homolog B |
MET | Mesenchymal-epithelial transition |
PI3K | Phosphoinositide 3-kinase |
HGF | Hepatocyte growth factor |
MAPK | Mitogen-activated protein kinase |
FISH | Fluorescent in-situ hybridization |
TKI | Tyrosine-kinase inhibitors |
PFS | Progression-free survival |
OS | Overall survival |
ORR | Overall response rate |
HR | Hazard ratio |
CI | Confidence interval |
IV | Intravenous |
IHC | Immunohistochemistry |
DCR | Disease control rate |
DOR | Duration of response |
CNS | Central nervous system |
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Drugs | PFS (Median, Months) | OS (Median, Months) | DOR (Median, Months) | ORR (Median, %) | DCR (Median, %) | References |
---|---|---|---|---|---|---|
Emibetuzumab + erlotinib | 9.30 * | 34.40 * | 9.50 | 84.50 | 10,000% | [8] |
Erlotinib | 9.50 * | 25.40 * | 11.10 | 65.70 | 98.60 | [8] |
Onartuzumab + erlotinib (highest quartile) | 4.37 | ** | ** | ** | ** | [10] |
Placebo + erlotinib | 2.59 | ** | ** | ** | ** | [10] |
Onartuzumab + paclitaxel + carboplatin/cisplatin | 4.90 | 9.10 | ** | 40.00 * | ** | [11] |
Placebo + paclitaxel + carboplatin/cisplatin | 4.90 | 8.50 | ** | 43.40 * | ** | [11] |
Onartuzumab + bevacizumab-based chemotherapy | 5.00 | *** | ** | 51.50 * | ** | [12] |
Placebo + bevacizumab-based chemotherapy | 6.80 | 16.50 | ** | 44.80 * | ** | [12] |
Onartuzumab + pemetrexed-based chemotherapy | 4.90 | 8.50 | ** | 28.60 * | ** | [12] |
Placebo + pemetrexed-based chemotherapy | 5.10 | 13.70 | ** | 36.10 * | ** | [12] |
Onartuzumab + erlotinib | 2.70 * | 6.80 | ** | 8.40 | ** | [13] |
Placebo + erlotinib | 2.60 * | 9.10 | ** | 9.60 | ** | [13] |
Drugs | PFS (Median, Months) | OS (Median, Months) | DOR (Median, Months) | ORR (Median, %) | DCR (Median, %) | References |
---|---|---|---|---|---|---|
Tivantinib + erlotinib | 3.60 | 8.50 * | 10.10 | 10.30 | 45.80 | [17] |
Placebo + erlotinib | 1.90 | 7.80 * | 11.90 | 6.50 | 32.00 | [17] |
Tivantinib + erlotinib | 13.00 | 25.50 | 12.70 | 60.70 | ** | [18] |
Placebo + erlotinib | 7.50 | 20.30 | 9.80 | 43.30 | ** | [18] |
Tivantinib + erlotinib | 1.70 * | 6.80 | ** | 0 | 49.00 | [19] |
Single-agent chemotherapy | 4.30 * | 8.50 | ** | 4.40 | 62.20 | [19] |
Tivantinib + erlotinib | 2.90 | 12.70 | ** | ** | ** | [20] |
Placebo + erlotinib | 2.00 | 11.10 | ** | ** | ** | [20] |
Cabozantinib | 5.50 | 9.90 | 7.00 | 28.00 | ** | [22] |
Cabozantinib | 4.30 | 9.20 | ** | ** | ** | [23] |
Erlotinib | 1.80 | 5.10 | ** | ** | ** | [23] |
Cabozantinib + erlotinib | 4.70 | 13.30 | ** | ** | ** | [23] |
Cabozantinib | 2.40 * | ** | 6.90 | 10.00 | 38.30 | [24] |
Cabozantinib | 2.40 * | 7.70 | ** | 10.00 | 38.00 | [25] |
Crizotinib | 15.90 | 32.50 | 19.70 | 71.70 | 80.30 | [28] |
Crizotinib | 10.20 | 20.00 | 11.10 | ** | ** | [30] |
Alectinib | *** | 30.00 | ** | ** | ** | [30] |
Crizotinib | 10.90 | ** | ** | ** | ** | [31] |
Alectinib | 34.80 | ** | ** | ** | ** | [31] |
Capmatinib (cohort 4) | 5.42 | ** | 9.72 | 39.10 | ** | [33] |
Capmatinib (cohort 5b) | 9.13 | ** | 8.41 | 71.40 | ** | [33] |
Capmatinib + gefitinib (GCN ≥ 6) | 5.50 | ** | ** | 47.00 | ** | [35] |
Capmatinib + gefitinib (all patients) | 5.49 | ** | 5.60 | 29.00 | 73.00 | [35] |
Study Title | Status | Condition | Intervention | Phase | Locations | Enrollment | Start | End |
---|---|---|---|---|---|---|---|---|
Phase 1 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET | R | Advanced solid tumors, metastatic solid tumors, MET gene alterations | TPX-0022 | 1 | UC Irvine Chao Family Comprehensive Center (CA, US) UC San Diego Moores Cancer Center (CA, US) Sarah Connor Research Institute at HealthONE (CO, US) and 5 more | 120 | Aug 2019 | Nov 2023 |
Study of Crizotinib for ROS1 and MET Activated Lung Cancer | NYR | Non-squamous NSCLC, stage IV NSCLC, ROS1 gene rearrangement, MET activating mutation, MET amplification | Crizotinib | 2 | Princess Margaret Cancer Centre (Toronto, ON, Canada) | 50 | Dec 2019 | Jun 2025 |
Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (SAVANNAH) | R | Carcinoma | Osimertinib Savolitinib | 2 | La Jolla, CA, US Los Angeles, CA, US) Sacramento, CA, US and 97 more | 192 | Jan 2019 | Jul 2022 |
A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor | R | Malignant NSCLC stage IV | Capmatinib | 2 | Massachusetts General Hospital (Boston, MA, US) | 20 | May 2016 | Dec 2020 |
Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer | R | NSCLC carcinoma | Capmatinib | 2 | UAMS (Little Rock, AR, US) Pacific Shores Medical Group (Long Beach, CA, US) Los Angeles Hematology/Oncology Medical Group (CA, US) and 153 more | 373 | Jun 2015 | Sep 2022 |
Capmatinib in Patients With Non-small Cell Lung Cancer Harboring cMET exon14 Skipping Mutation | R | Metastatic NSCLC MET gene mutation | Capmatinib | Asan Medical Center (Seoul, Republic of Korea) | 27 | Oct 2018 | Jun 2022 | |
Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterations (VISION) | R | Stage IIIB/IV NSCLC with METex14 skipping alterations or MET amplification | Tepotinib | 2 | City of Hope Cancer Center (Duarte, CA, US) Torrance Health Association (Redondo Beach, CA, US) and 95 more | 280 | Sep 2016 | Feb 2023 |
A Study of Tepotinib Plus Osimertinib in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Relapsed Mesenchymal-epithelial Transition Factor (MET) Amplified Non-small Cell Lung Cancer (NSCLC) | R | NSCLC | Tepotinib Osimertinib | 2 | Compassionate Care Research Group Inc (Fountain Valley, CA, US) St. Louis Cancer Care (Bridgeton, MO, US) Tennessee Oncology (Nashville, TN, US) | 90 | Sep 2019 | Mar 2022 |
CABozantinib in Non-Small Cell Lung Cancer (NSCLC) Patients With MET Deregulation (CABinMET) | R | NSCLC | Cabozantinib | 2 | AOS Giuseppe Moscati (Avellino, AV, Italy) IRCCS Oncologico Giovanni Paolo II (Bari, BA, Italy) AOU Careggi (Firenze, FI, Italy) and 17 more | 25 | Sep 2018 | Sep 2020 |
Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer | R | NSCLC | Crizotinib | 2 | University of Colorado Denver (Aurora, CO, US) | 18 | Dec 2017 | Oct 2021 |
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De Mello, R.A.; Neves, N.M.; Amaral, G.A.; Lippo, E.G.; Castelo-Branco, P.; Pozza, D.H.; Tajima, C.C.; Antoniou, G. The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer. J. Clin. Med. 2020, 9, 1918. https://doi.org/10.3390/jcm9061918
De Mello RA, Neves NM, Amaral GA, Lippo EG, Castelo-Branco P, Pozza DH, Tajima CC, Antoniou G. The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer. Journal of Clinical Medicine. 2020; 9(6):1918. https://doi.org/10.3390/jcm9061918
Chicago/Turabian StyleDe Mello, Ramon Andrade, Nathália Moisés Neves, Giovanna Araújo Amaral, Estela Gudin Lippo, Pedro Castelo-Branco, Daniel Humberto Pozza, Carla Chizuru Tajima, and Georgios Antoniou. 2020. "The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer" Journal of Clinical Medicine 9, no. 6: 1918. https://doi.org/10.3390/jcm9061918