Liquid Biopsy in EGFR-Mutated Advanced NSCLC from T790M to MET Amplification: Clinical Implications and Possibilities in the Resistance Setting
Abstract
:1. Current State of the Art for the Treatment of EGFR-Mutated Advanced NSCLC: The Role of Osimertinib
2. Current State of the Art for the Treatment of EGFR-Mutated Advanced NSCLC: The Role of Liquid Biopsy
3. Challenges and Opportunities Ahead
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Singh, N.; Temin, S.; Baker, S.; Blanchard, E.; Brahmer, J.R.; Celano, P.; Duma, N.; Ellis, P.M.; Elkins, I.B.; Haddad, R.Y.; et al. Therapy for Stage IV Non–Small-Cell Lung Cancer with Driver Alterations: ASCO Living Guideline. J. Clin. Oncol. 2022, 40, 3310–3322. [Google Scholar] [CrossRef] [PubMed]
- Planchard, D.; Popat, S.; Kerr, K.; Novello, S.; Smit, E.F.; Faivre-Finn, C.; Mok, T.S.; Reck, M.; Van Schil, P.E.; Hellmann, M.D.; et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018, 29 (Suppl. S4), iv192–iv237. Available online: https://www.esmo.org/content/download/347819/6934778/1/ESMO-CPG-mNSCLC-15SEPT2020.pdf (accessed on 19 November 2022). [CrossRef] [PubMed]
- Roeper, J.; Lueers, A.; Falk, M.; Schatz, S.; Tiemann, M.; Wesseler, C.; Wiest, G.; Sackmann, S.; Ukena, D.; Heukamp, L.; et al. Risk of not receiving second-line therapy is high in EGFR mt+ patients: Real-world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients. Ann. Oncol. 2019, 30 (Suppl. S2), ii48. [Google Scholar] [CrossRef]
- Nieva, J.; Reckamp, K.L.; Potter, D.; Taylor, A.; Sun, P. Retrospective Analysis of Real-World Management of EGFR-Mutated Advanced NSCLC, After First-Line EGFR-TKI Treatment: US Treatment Patterns, Attrition, and Survival Data. Drugs-Real World Outcomes 2022, 9, 333–345. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Wang, J.; Zhang, G.; Li, Y.; Lin, L.; Yang, H.; Zhou, J.; Zhang, L.; Lv, D. Detection of plasma T790M mutation after the first generation EGFR-TKI resistance of non-small cell lung cancer in the real world. J. Thorac. Dis. 2020, 12, 550–557. [Google Scholar] [CrossRef] [PubMed]
- Ko, R.; Kenmotsu, H.; Serizawa, M.; Koh, Y.; Wakuda, K.; Ono, A.; Taira, T.; Naito, T.; Murakami, H.; Isaka, M.; et al. Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients. BMC Cancer 2016, 16, 864. [Google Scholar] [CrossRef] [PubMed]
- Pereira, I.; Gaspar, C.; Pina, M.; Azevedo, I.; Rodrigues, A. Real-World T790M Mutation Frequency and Impact of Rebiopsy in Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer. Cureus 2020, 12, e12128. [Google Scholar] [CrossRef] [PubMed]
- Del Re, M.; Petrini, I.; Mazzoni, F.; Valleggi, S.; Gianfilippo, G.; Pozzessere, D.; Chella, A.; Crucitta, S.; Rofi, E.; Restante, G.; et al. Incidence of T790M in Patients with NSCLC Progressed to Gefitinib, Erlotinib, and Afatinib: A Study on Circulating Cell-free DNA. Clin. Lung Cancer 2020, 21, 232–237. [Google Scholar] [CrossRef]
- Kuiper, J.L.; Heideman, D.A.; Thunnissen, E.; Paul, M.A.; van Wijk, A.W.; Postmus, P.E.; Smit, E.F. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer 2014, 85, 19–24. [Google Scholar] [CrossRef]
- Lee, C.-S.; Milone, M.; Seetharamu, N. Osimertinib in EGFR-Mutated Lung Cancer: A Review of the Existing and Emerging Clinical Data. OncoTargets Ther. 2021, 14, 4579–4597. [Google Scholar] [CrossRef]
- Rocco, D.; Battiloro, C.; Della Gravara, L.; Gridelli, C. Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Mutation: First Line Treatment and Beyond. Rev. Recent Clin. Trials 2019, 14, 120–128. [Google Scholar] [CrossRef] [PubMed]
- Cortellini, A.; Ficorella, C.; Crisci, R.; Divisi, D. A reflection on the actual place of osimertinib in the treatment algorithm of EGFR-positive non-small cell lung cancer patients. J. Thorac. Dis. 2020, 12, 6107–6111. [Google Scholar] [CrossRef] [PubMed]
- Melosky, B.; Banerji, S.; Blais, N.; Chu, Q.; Juergens, R.; Leighl, N.B.; Liu, G.; Cheema, P. Canadian Consensus: A New Systemic Treatment Algorithm for Advanced EGFR-Mutated Non-Small-Cell Lung Cancer. Curr. Oncol. 2020, 27, e146–e155. [Google Scholar] [CrossRef] [PubMed]
- Soria, J.-C.; Ohe, Y.; Vansteenkiste, J.; Reungwetwattana, T.; Chewaskulyong, B.; Lee, K.H.; Dechaphunkul, A.; Imamura, F.; Nogami, N.; Kurata, T.; et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 113–125. [Google Scholar] [CrossRef]
- Ramalingam, S.S.; Vansteenkiste, J.; Planchard, D.; Cho, B.C.; Gray, J.E.; Ohe, Y.; Zhou, C.; Reungwetwattana, T.; Cheng, Y.; Chewaskulyong, B.; et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N. Engl. J. Med. 2020, 382, 41–50. [Google Scholar] [CrossRef] [PubMed]
- Mok, T.S.; Wu, Y.-L.; Ahn, M.-J.; Garassino, M.C.; Kim, H.R.; Ramalingam, S.S.; Shepherd, F.A.; He, Y.; Akamatsu, H.; Theelen, W.S.; et al. Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer. N. Engl. J. Med. 2017, 376, 629–640. [Google Scholar] [CrossRef]
- Papadimitrakopoulou, V.A.; Mok, T.S.; Han, J.Y.; Ahn, M.J.; Delmonte, A.; Ramalingam, S.S.; Kim, S.W.; Shepherd, F.A.; Laskin, J.; He, Y.; et al. Osimertinib versus platinum–pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann. Oncol. 2020, 31, 1536–1544. [Google Scholar] [CrossRef]
- Goldman, J.; Noor, Z.; Remon, J.; Besse, B.; Rosenfeld, N. Are liquid biopsies a surrogate for tissue EGFR testing? Ann. Oncol. 2018, 29 (Suppl. S1), i38–i46. [Google Scholar] [CrossRef] [PubMed]
- Malapelle, U.; Tiseo, M.; Vivancos, A.; Kapp, J.; Serrano, M.J.; Tiemann, M. Liquid Biopsy for Biomarker Testing in Non-Small Cell Lung Cancer: A European Perspective. J. Mol. Pathol. 2021, 2, 22. [Google Scholar] [CrossRef]
- Lone, S.N.; Nisar, S.; Masoodi, T.; Singh, M.; Rizwan, A.; Hashem, S.; El-Rifai, W.; Bedognetti, D.; Batra, S.K.; Haris, M.; et al. Liquid biopsy: A step closer to transform diagnosis, prognosis and future of cancer treatments. Mol. Cancer 2022, 21, 79. [Google Scholar] [CrossRef]
- Hofman, P. Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice. Cells 2021, 10, 168. [Google Scholar] [CrossRef] [PubMed]
- Park, S.; Olsen, S.; Ku, B.M.; Lee, M.; Jung, H.; Sun, J.; Lee, S.; Ahn, J.S.; Park, K.; Choi, Y.; et al. High concordance of actionable genomic alterations identified between circulating tumor DNA–based and tissue—Based next—Generation sequencing testing in advanced non–small cell lung cancer: The Korean Lung Liquid Versus Invasive Biopsy Program. Cancer 2021, 127, 3019–3028. [Google Scholar] [CrossRef] [PubMed]
- Reck, M.; Hagiwara, K.; Han, B.; Tjulandin, S.; Grohé, C.; Yokoi, T.; Morabito, A.; Novello, S.; Arriola, E.; Molinier, O.; et al. ctDNA Determination of EGFR Mutation Status in European and Japanese Patients with Advanced NSCLC: The ASSESS Study. J. Thorac. Oncol. 2016, 11, 1682–1689. [Google Scholar] [CrossRef] [PubMed]
- Sabari, J.K.; Offin, M.; Stephens, D.; Ni, A.; Lee, A.; Pavlakis, N.; Clarke, S.; I Diakos, C.; Datta, S.; Tandon, N.; et al. A Prospective Study of Circulating Tumor DNA to Guide Matched Targeted Therapy in Lung Cancers. Gynecol. Oncol. 2019, 111, 575–583. [Google Scholar] [CrossRef] [PubMed]
- Mosele, F.; Remon, J.; Mateo, J.; Westphalen, C.; Barlesi, F.; Lolkema, M.; Normanno, N.; Scarpa, A.; Robson, M.; Meric-Bernstam, F.; et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: A report from the ESMO Precision Medicine Working Group. Ann. Oncol. 2020, 31, 1491–1505. [Google Scholar] [CrossRef] [PubMed]
- Kalemkerian, G.P.; Narula, N.; Kennedy, E.B.; Biermann, W.A.; Donington, J.; Leighl, N.B.; Lew, M.; Pantelas, J.; Ramalingam, S.S.; Reck, M.; et al. Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J. Clin. Oncol. 2018, 36, 911–919. [Google Scholar] [CrossRef]
- Rolfo, C.; Mack, P.; Scagliotti, G.V.; Aggarwal, C.; Arcila, M.E.; Barlesi, F.; Bivona, T.; Diehn, M.; Dive, C.; Dziadziuszko, R.; et al. Liquid Biopsy for Advanced NSCLC: A Consensus Statement from the International Association for the Study of Lung Cancer. J. Thorac. Oncol. 2021, 16, 1647–1662. [Google Scholar] [CrossRef]
- Kwapisz, D. The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer? Ann. Transl. Med. 2017, 5, 46. [Google Scholar] [CrossRef]
- Canale, M.; Pasini, L.; Bronte, G.; Delmonte, A.; Cravero, P.; Crinò, L.; Ulivi, P. Role of liquid biopsy in oncogene-addicted non-small cell lung cancer. Transl. Lung Cancer Res. 2019, 8 (Suppl. S3), S265–S279. [Google Scholar] [CrossRef]
- Oxnard, G.R.; Paweletz, C.P.; Kuang, Y.; Mach, S.L.; O’Connell, A.; Messineo, M.M.; Luke, J.J.; Butaney, M.; Kirschmeier, P.; Jackman, D.M.; et al. Noninvasive Detection of Response and Resistance in EGFR-Mutant Lung Cancer Using Quantitative Next-Generation Genotyping of Cell-Free Plasma DNA. Clin. Cancer Res. 2014, 20, 1698–1705. [Google Scholar] [CrossRef]
- Mok, T.; Wu, Y.-L.; Lee, J.S.; Yu, C.-J.; Sriuranpong, V.; Sandoval-Tan, J.; Ladrera, G.; Thongprasert, S.; Srimuninnimit, V.; Liao, M.; et al. Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy. Clin. Cancer Res. 2015, 21, 3196–3203. [Google Scholar] [CrossRef] [PubMed]
- Lazzari, C.; Gregorc, V.; Karachaliou, N.; Rosell, R.; Santarpia, M. Mechanisms of resistance to osimertinib. J. Thorac. Dis. 2020, 12, 2851–2858. [Google Scholar] [CrossRef] [PubMed]
- Leonetti, A.; Sharma, S.; Minari, R.; Perego, P.; Giovannetti, E.; Tiseo, M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br. J. Cancer 2019, 121, 725–737. [Google Scholar] [CrossRef]
- Yang, J.-J.; Fang, J.; Shu, Y.-Q.; Chang, J.-H.; Chen, G.-Y.; He, J.X.; Li, W.; Liu, X.-Q.; Yang, N.; Zhou, C.; et al. A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer. Investig. New Drugs 2021, 39, 477–487. [Google Scholar] [CrossRef] [PubMed]
- Sequist, L.V.; Han, J.-Y.; Ahn, M.-J.; Cho, B.C.; Yu, H.; Kim, S.-W.; Yang, J.C.-H.; Lee, J.S.; Su, W.-C.; Kowalski, D.; et al. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: Interim results from a multicentre, open-label, phase 1b study. Lancet Oncol. 2020, 21, 373–386. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.-L.; Cheng, Y.; Zhou, J.; Lu, S.; Zhang, Y.; Zhao, J.; Kim, D.-W.; Soo, R.A.; Kim, S.-W.; Pan, H.; et al. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): An open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir. Med. 2020, 8, 1132–1143, Erratum in Lancet Respir. Med. 2020, 8, e59. [Google Scholar] [CrossRef] [PubMed]
- Park, K.; Zhou, J.; Kim, D.-W.; Ahmad, A.; Soo, R.; Bruns, R.; Straub, J.; Johne, A.; Scheele, J.; Yang, J.-H.; et al. Tepotinib plus gefitinib in patients with MET-amplified EGFR-mutant NSCLC: Long-term outcomes of the INSIGHT study. Ann. Oncol. 2019, 30 (Suppl. S9), ix159. [Google Scholar] [CrossRef]
- Wu, Y.-L.; Zhang, L.; Kim, D.-W.; Liu, X.; Lee, D.H.; Yang, J.C.-H.; Ahn, M.-J.; Vansteenkiste, J.F.; Su, W.-C.; Felip, E.; et al. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor–Dysregulated Non–Small-Cell Lung Cancer. J. Clin. Oncol. 2018, 36, 3101–3109, Erratum in J. Clin. Oncol. 2019, 37, 261. [Google Scholar] [CrossRef]
- Wu, Y.-L.; Zhang, L.; Kim, D.-W.; Liu, X.; Lee, D.H.; Yang, J.C.-H.; Ahn, M.-J.; Vansteenkiste, J.F.; Su, W.-C.; Felip, E.; et al. Phase 1b/2 study of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated non-small cell lung cancer who received prior therapy: Final overall survival and safety. J. Clin. Oncol. 2021, 39 (Suppl. S15), 9048. [Google Scholar] [CrossRef]
- A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients with EGFRm+ and MET Amplified Advanced NSCLC (CoC); clinicaltrials.gov [Internet], ClinicalTrials.gov Identifier: NCT04606771. Available online: https://www.clinicaltrials.gov/ct2/show/NCT04606771?term=Savolitinib&cond=NSCLC&draw=3&rank=4 (accessed on 19 November 2022).
- A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2); Clinicaltrials.gov [Internet] ClinicalTrials.gov Identifier: NCT03940703. Available online: https://www.clinicaltrials.gov/ct2/show/NCT03940703?term=tepotinib&cond=Nsclc&draw=2&rank=2 (accessed on 19 November 2022).
- Yu, H.; Goldberg, S.; Le, X.; Piotrowska, Z.; Smith, P.; Mensi, I.; Kirova, B.; Chmielecki, J.; Li-Sucholeicki, X.; Szekeres, P.; et al. P2.01-22 ORCHARD: A Phase II Platform Study in Patients with Advanced NSCLC Who Have Progressed on First-Line Osimertinib Therapy. J. Thorac. Oncol. 2019, 14, S647. [Google Scholar] [CrossRef]
- Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD) (ORCHARD); Clinicaltrials.org [internet]. ClinicalTrials.gov Identifier: NCT03944772. Available online: https://www.clinicaltrials.gov/ct2/show/NCT03944772 (accessed on 19 November 2022).
- Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (SAVANNAH); Clinicaltrials.org [internet]. ClinicalTrials.gov Identifier: NCT03778229. Available online: https://www.clinicaltrials.gov/ct2/show/NCT03778229 (accessed on 19 November 2021).
- Tagrisso plus Savolitinib Demonstrated 49% Objective Response Rate in Lung Cancer Patients with High Levels of MET Overexpression and/or Amplification in SAVANNAH Phase II Trial; AstraZeneca.com [Internet]. Available online: https://www.astrazeneca.com/media-centre/press-releases/2022/tagrisso-plus-savolitinib-demonstrated-49-objective-response-rate-in-lung-cancer-patients-in-savannah-phase-ii-trial.html (accessed on 19 November 2022).
- Bonanno, L.; Maso, A.D.; Pavan, A.; Zulato, E.; Calvetti, L.; Pasello, G.; Guarneri, V.; Conte, P.; Indraccolo, S. Liquid biopsy and non-small cell lung cancer: Are we looking at the tip of the iceberg? Br. J. Cancer 2022, 127, 383–393. [Google Scholar] [CrossRef]
- Wang, Z.; Yang, J.-J.; Huang, J.; Ye, J.-Y.; Zhang, X.-C.; Tu, H.-Y.; Han-Zhang, H.; Wu, Y.-L. Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance. J. Thorac. Oncol. 2017, 12, 1723–1727. [Google Scholar] [CrossRef] [PubMed]
- Arulananda, S.; Do, H.; Musafer, A.; Mitchell, P.; Dobrovic, A.; John, T. Combination Osimertinib and Gefitinib in C797S and T790M EGFR-Mutated Non–Small Cell Lung Cancer. J. Thorac. Oncol. 2017, 12, 1728–1732. [Google Scholar] [CrossRef] [PubMed]
- Mondelo-Macía, P.; Rodríguez-López, C.; Valiña, L.; Aguín, S.; León-Mateos, L.; García-González, J.; Abalo, A.; Rapado-González, O.; Suárez-Cunqueiro, M.; Díaz-Lagares, A.; et al. Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients. Cells 2020, 9, 522. [Google Scholar] [CrossRef] [PubMed]
- Smit, E.F.; Dooms, C.; Raskin, J.; Nadal, E.; Tho, L.M.; Le, X.; Mazieres, J.; Hin, H.S.; Morise, M.; Zhu, V.W.; et al. INSIGHT 2: A phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance. Future Oncol. 2022, 18, 1039–1054. [Google Scholar] [CrossRef]
- Schildhaus, H.-U.; Schultheis, A.M.; Rüschoff, J.; Binot, E.; Merkelbach-Bruse, S.; Fassunke, J.; Schulte, W.; Ko, Y.-D.; Schlesinger, A.; Bos, M.; et al. MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung. Clin. Cancer Res. 2015, 21, 907–915. [Google Scholar] [CrossRef]
- Tran, T.N.; Selinger, C.I.; Kohonen-Corish, M.R.; McCaughan, B.; Kennedy, C.; O’Toole, S.A.; Cooper, W.A. Alterations of MET Gene Copy Number and Protein Expression in Primary Non–Small-Cell Lung Cancer and Corresponding Nodal Metastases. Clin. Lung Cancer 2016, 17, 30–38. [Google Scholar] [CrossRef]
- Camidge, D.R.; Otterson, G.A.; Clark, J.W.; Ou, S.-H.I.; Weiss, J.; Ades, S.; Shapiro, G.I.; Socinski, M.A.; Murphy, D.A.; Conte, U.; et al. Crizotinib in Patients With MET-Amplified NSCLC. J. Thorac. Oncol. 2021, 16, 1017–1029. [Google Scholar] [CrossRef]
- Fischer, A.; Bankel, L.; Hiltbrunner, S.; Rechsteiner, M.; Rüschoff, J.H.; Rushing, E.J.; Britschgi, C.; Curioni-Fontecedro, A. Mutational Landscape and Expression of PD-L1 in Patients with Non-Small Cell Lung Cancer Harboring Genomic Alterations of the MET gene. Target. Oncol. 2022, 17, 683–694. [Google Scholar] [CrossRef]
- Peng, L.-X.; Jie, G.-L.; Li, A.-N.; Liu, S.-Y.; Sun, H.; Zheng, M.-M.; Zhou, J.-Y.; Zhang, J.-T.; Zhang, X.-C.; Zhou, Q.; et al. MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors. Exp. Hematol. Oncol. 2021, 10, 52. [Google Scholar] [CrossRef]
- Schubart, C.; Stöhr, R.; Tögel, L.; Fuchs, F.; Sirbu, H.; Seitz, G.; Seggewiss-Bernhardt, R.; Leistner, R.; Sterlacci, W.; Vieth, M.; et al. MET Amplification in Non-Small Cell Lung Cancer (NSCLC)—A Consecutive Evaluation Using Next-Generation Sequencing (NGS) in a Real-World Setting. Cancers 2021, 13, 5023. [Google Scholar] [CrossRef] [PubMed]
- Qin, K.; Hong, L.; Zhang, J.; Le, X. MET Amplification as a Resistance Driver to TKI Therapies in Lung Cancer: Clinical Challenges and Opportunities. Cancers 2023, 15, 612. [Google Scholar] [CrossRef] [PubMed]
- Russano, M.; Napolitano, A.; Ribelli, G.; Iuliani, M.; Simonetti, S.; Citarella, F.; Pantano, F.; Dell’aquila, E.; Anesi, C.; Silvestris, N.; et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: The potentiality of blood samples. J. Exp. Clin. Cancer Res. 2020, 39, 95, Erratum in J. Exp. Clin. Cancer Res. 2020, 39, 120. [Google Scholar] [CrossRef] [PubMed]
- Fernandes, M.G.O.; Sousa, C.; Reis, J.P.; Cruz-Martins, N.; Moura, C.S.; Guimarães, S.; Justino, A.; Pina, M.J.; Magalhães, A.; Queiroga, H.; et al. Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic. Cells 2021, 10, 1912. [Google Scholar] [CrossRef]
Clinical Trial Identifier | Phase | Subset of Patients | Experimental Arm | Control Arm | Primary Objective(s) | Study Completion Date |
---|---|---|---|---|---|---|
NCT04606771 | II | EGFR+ MET-amplified progressing after osimertinib | Savolitinib + osimertinib | Savolitinib + placebo | ORR | February 2024 |
NCT03940703 (INSIGHT 2) | II | EGFR+ MET-amplified progressing after upfront osimertinib | Tepotinib ± osimertinib | / | DLTs and ORR | March 2023 |
NCT03944772 (ORCHARD; group A) | II | EGFR+ progressing after upfront osimertinib presenting different resistance mechanisms | Osimertinib + savolitinib (MET amplification) Osimertinib + gefitinib (C797S mutation) Osimertinib + necitumumab (EGFR-amplification) Osimertinib + alectinib (ALK-rearrangement) Osimertinib + selpercatinib (RET-rearrangement) | / | ORR | November 2025 |
NCT03778229 (SAVANNAH) | II | EGFR+ MET-amplified/overexpressed progressing after upfront osimertinib | Savolitinib + osimertinib | / | ORR | February 2025 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Della Gravara, L.; Battiloro, C.; Avellino, A.; Caputo, F.; D’Aniello, C.; Rocco, D. Liquid Biopsy in EGFR-Mutated Advanced NSCLC from T790M to MET Amplification: Clinical Implications and Possibilities in the Resistance Setting. J. Mol. Pathol. 2023, 4, 81-88. https://doi.org/10.3390/jmp4020009
Della Gravara L, Battiloro C, Avellino A, Caputo F, D’Aniello C, Rocco D. Liquid Biopsy in EGFR-Mutated Advanced NSCLC from T790M to MET Amplification: Clinical Implications and Possibilities in the Resistance Setting. Journal of Molecular Pathology. 2023; 4(2):81-88. https://doi.org/10.3390/jmp4020009
Chicago/Turabian StyleDella Gravara, Luigi, Ciro Battiloro, Aniello Avellino, Francesca Caputo, Carmine D’Aniello, and Danilo Rocco. 2023. "Liquid Biopsy in EGFR-Mutated Advanced NSCLC from T790M to MET Amplification: Clinical Implications and Possibilities in the Resistance Setting" Journal of Molecular Pathology 4, no. 2: 81-88. https://doi.org/10.3390/jmp4020009