Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Complex EGFR Mutations
3.2. Actionable Concomitant Oncogenic Driver Mutations
3.2.1. ALK
3.2.2. KRAS
3.2.3. ROS-1
3.2.4. MET
3.2.5. BRAF
3.2.6. RET
3.3. TP53, PTEN, PIK3CA, CDKN2A and RB1
3.4. Methods of Detection
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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---|---|---|---|---|---|---|---|
Belardinilli et al. [17] | Case Report | Caucasian | 1 | EGFR complex | NGS | tumor tissue | 40.30% 41.30% 67.50% |
Benesova et al. [18] | Case Series | Caucasian | 4 | EGFR+KRAS EGFR complex | Sanger | tumor tissue | N/A |
Fan et al. [19] | Case Report | Asian | 1 | EGFR+ALK | NGS | tumor tissue | EGFR 15.58% ALK 6.42% |
Lammers et al. [20] | Case Report | Caucasian | 1 | EGFR+PIK3CA | SNapShot PCR | tumor tissue | N/A |
Lee et al. [21] | Case Series | Asian | 12 | EGFR+KRAS EGFR+ALK | Sanger; Real Time PCR after PNA; FISH and IHC | tumor tissue | N/A |
Miyanaga et al. [22] | Case Report | Asian | 1 | EGFR+ALK | PNA-LNA PCR clamp method, FISH and IHC | tumor tissue | N/A |
Sweis et al. [23] | Case Series | Caucasian | 4 | EGFR+ALK | N/A | N/A | N/A |
Thumallapally et al. [24] | Case Report | Caucasian | 1 | EGFR+ALK | FISH, direct sequencing | tumor tissue | N/A |
Zhu et al. [25] | Case Report | Asian | 1 | EGFR+ROS-1 | NGS, PCR and FISH | tumor tissue | N/A |
Yang et al. [26] | Case Series | Asian | 13 | EGFR+ALK | IHC, FISH, Sanger, RT-PCR and RACE-PCR sequencing | tumor tissue | N/A |
Hou et al. [27] | Retrospective | Asian | 59 | EGFR+TP53 EGFR+RB1 | NGS | tumor tissue | N/A |
Zhu et al. [28] | Retrospective | Asian | 2 | EGFR+ALK | FISH, RT-PCR | tumor tissue | N/A |
Li et al. [29] | Retrospective | Asian | 149 | EGFR+ PIK3CA EGFR complex EGFR+KRAS EGFR+BRAF | SurPlex®-xTAG70plex-EGFR liquidchip | tumor tissue | N/A |
Liang et al. [30] | Retrospective | Asian | 403 | EGFR complex | NGS | tumor tissue + plasma | N/A |
Liu et al. [31] | Retrospective | Asian | 21 | EGFR+ALK | NGS | tumor tissue + plasma | N/A |
Nardo et al. [32] | Retrospective | Caucasian | 3 | EGFR+KRAS | ddPCR | tumor tissue + plasma | KRAS <0.2 |
Rachiglio et al. [33] | Retrospective | Caucasian | 38 | EGFR+KRAS EGFR+BRAF EGFR+MET EGFR+TP53 EGFR+PIK3CA | NGS, ddPCR | tumor tissue + plasma | KRAS 2–38% EGFR ≥ 2% |
Sato et al. [34] | Retrospective | Asian | 43 | EGFR complex EGFR+TP53 EGFR+RB1 | NGS | tumor tissue | N/A |
VanderLaan et al. [35] | Retrospective | Caucasian | 19 | EGFR+TP53 EGFR+PIK3CA EGFR+PTEN | NGS, Sanger | tumor tissue | N/A |
Wu et al. [36] | Retrospective | Asian | 12 | EGFR+PIK3CA | Sanger, RT-PCR | tumor tissue | N/A |
Zheng et al. [37] | Retrospective | Asian | 11 | EGFR+TP53 | NGS | tumor tissue | N/A |
Zhuang et al. [38] | Retrospective | Asian | 43 | EGFR+ALK EGFR+ROS-1 EGFR+KRAS EGFR+BRAF | ARMS | tumor tissue | N/A |
Huang et al. [39] | Prospective | Asian | 18 | EGFR+TP53/PTEN EGFR+PIK3CA | N/A | N/A | N/A |
Zhang et al. [40] | Prospective | Asian | N/A | EGFR+TP53 | NGS | N/A | N/A |
Canale et al. [41] | Retrospective | Caucasian | 136 | EGFR+TP53 | Sanger, MassARRAY, NGS | tumor tissue | N/A |
Chang et al. [42] | Retrospective | Asian | 26 | EGFR+ALK EGFR+TP53 EGFR+PIK3CA EGFR+CDKN2A | NGS, CNV | tumor tissue | N/A |
Chen et al. [43] | Retrospective | Asian | 16 | EGFR complex EGFR+ALK EGFR+KRAS EGFR+PIK3CA EGFR+TP53 | NGS | tumor tissue + plasma | N/A |
De Marchi et al. [44] | Retrospective | Caucasian | 47 | EGFR complex EGFR+KRAS EGFR+PIK3CA | NGS, Sanger, SNP array | tumor tissue | N/A |
Eng et al. [45] | Retrospective | Caucasian | 13 | EGFR+PIK3CA | mutation hotspot testing, FISH, multiplex sizing assays | tumor tissue | N/A |
Chevallier et al. [46] | Retrospective | Caucasian | 20 | EGFR+TP53 EGFR+MET EGFR+KRAS EGFR+PIK3CA EGFR+PTEN | NGS | tumor tissue | N/A |
Hu et al. [47] | Retrospective | Asian | 21 | EGFR+ALK EGFR+PIK3CA EGFR+KRAS EGFR+ROS-1 EGFR+RET EGFR+HER2 | ARMS; adx-RT, mutation detection kit; fusion gene detection kit | tumor tissue | N/A |
Chen et al. [48] | Retrospective | Asian | 71 | EGFR complex EGFR+TP53 EGFR+ALK EGFR+BRAF EGFR+MET | NGS, ARMS | tumor tissue + plasma | N/A |
Lee et al. [49] | Retrospective | Asian | 7 | EGFR+ALK EGFR+MET EGFR+TP53 EGFR complex | FISH, NGS, Sanger | tumor tissue | N/A |
Zhang et al. [50] | Retrospective | Asian | 9 | EGFR complex EGFR+KRAS EGFR+PIK3CA | FISH, liquid chip platform | tumor tissue | N/A |
Wang et al. [51] | Retrospective | Asian | 17 | EGFR+PIK3CA | Sanger, FISH, IHC | tumor tissue | N/A |
Klempner et al. [52] | Case report | Asian | 2 | EGFR+RET | NGS | tumor tissue | 53% 54% 62% 18% |
Study | Concurrent Genomic Alteration | TKI | mPFS (mo.) | mOS (mo.) | Best Response |
---|---|---|---|---|---|
Belardinilli et al. [17] | EGFR complex | Afatinib | 8 | N/A | PR |
Benesova et al. [18] | EGFR+KRAS EGFR complex | Gefitinib Erlotinib | 6–12 | 5-23 | 3 PR 1 CR |
Fan et al. [19] | EGFR+ALK | Gefitinib Crizotinib | 18 | N/A | PR/SD |
Lammers et al. [20] | EGFR+PIK3CA | Erlotinib Afatinib PI3K inhibitor | 1–4 | N/A | SD/PR |
Lee et al. [21] | EGFR+KRAS EGFR+ALK | Gefitinib Erlotinib Crizotinib | 4–29 | N/A | SD/PR |
Miyanaga et al. [22] | EGFR+ALK | Gefitinib Erlotinib Crizotinib | 2–7 | N/A | SD |
Sweis et al. [23] | EGFR+ALK | Erlotinib Crizotinib | 2–12 | N/A | PR/PD |
Thumallapally et al. [24] | EGFR+ALK | Crizotinib | N/A | 3 wk | N/A |
Zhu et al. [25] | EGFR+ROS-1 | Adj CT | N/A | N/A | N/A |
Yang et al. [26] | EGFR+ALK | Gefitinib Erlotinib Crizotinib Afatinib | 12–27.4 | N/A | SD/PR/PD |
Hou et al. [27] | EGFR+TP53 EGFR+RB1 | Erlotinib Gefitinib Icotinib | 4–11 | 10–59 | N/A |
Zhu et al. [28] | EGFR+ALK | N/A | N/A | N/A | N/A |
Li et al. [29] | EGFR+PIK3CA EGFR complex EGFR+KRAS EGFR+BRAF | N/A | N/A | N/A | N/A |
Liang et al. [30] | EGFR Complex | N/A | N/A | N/A | N/A |
Liu et al. [31] | EGFR+ALK | Osimertinib Crizotinib Afatinib | 6–15 | N/A | N/A |
Nardo et al. [32] | EGFR+KRAS | Erlotinib Gefitinib Afatinib | 5 | 6 | PR |
Rachiglio et al. [33] | EGFR+KRAS EGFR+BRAF EGFR+MET EGFR+TP53 EGFR+PIK3CA | Erlotinib Gefitinib Afatinib | 7 | 15.5 | N/A |
Sato et al. [34] | EGFR complex EGFR+TP53 EGFR+RB1 | Gefitinib Erlotinib | N/A | N/A | PR |
VanderLaan et al. [35] | EGFR+TP53 EGFR+PIK3CA EGFR+PTEN | Erlotinib Gefitinib Afatinib | 6.5 | 15.5 | N/A |
Wu et al. [36] | EGFR+PIK3CA | Erlotinib Gefitinib Afatinib | 12 | 5.1 | PR |
Zheng et al. [37] | EGFR+TP53 | N/A | N/A | 23.9 | N/A |
Zhuang et al. [38] | EGFR+ALK EGFR+ROS-1 EGFR+KRAS EGFR+BRAF | Gefitinib Erlotinib Afatinib Icotinib Crizotinib Alectinib | 9.6 | N/A | PR |
Huang et al. [39] | EGFR+TP53/PTEN EGFR+PIK3CA | Anlotinib Icotinib | N/A | N/A | PR |
Zhang et al. [40] | EGFR+TP53 | Gefitinib Afatinib | N/A | N/A | N/A |
Canale et al. [41] | EGFR+TP53 | Erlotinib Gefitinib Afatinib | 5.8–12.9 | 29.7–19.5 | CR |
Chang et al. [42] | EGFR+ALK EGFR+TP53 EGFR+PIK3CA EGFR+CDKN2A | Erlotinib Gefitinib Afatinib | 1–24.2 | 5.4–57.6 | N/A |
Chen et al. [43] | EGFR complex EGFR+ALK EGFR+KRAS EGFR+PIK3CA EGFR+TP53 | Erlotinib Gefitinib Afatinib Osimertinib | 18.7 | N/A | CR |
De Marchi et al. [44] | EGFR complex EGFR+KRAS EGFR+PIK3CA | N/A | N/A | N/A | N/A |
Eng et al. [45] | EGFR+PIK3CA | Gefitinib | 7.8 | 18 | PR |
Chevallier et al. [46] | EGFR+TP53 EGFR+MET EGFR+KRAS EGFR+PIK3CA EGFR+PTEN | Erlotinib Gefitinib Afatinib Osimertinib | 6.8–11.6 | 7.7–16.8 | N/A |
Hu et al. [47] | EGFR+ALK EGFR+PIK3CA EGFR+KRAS EGFR+ROS-1 EGFR+RET EGFR+HER2 | Erlotinib Gefitinib Crizotinib Icotinib | 1–24 | 10–43 | PR/PD |
Chen et al. [48] | EGFR complex EGFR+TP53 EGFR+ALK EGFR+BRAF EGFR+MET | Erlotinib Gefitinib Icotinib | 6–24 | N/A | N/A |
Lee et al. [49] | EGFR+ALK EGFR+MET EGFR+TP53 EGFR complex | Erlotinib Gefitinib Crizotinib | 1–2.1 | 1–21.8 | N/A |
Zhang et al. [50] | EGFR complex EGFR+KRAS EGFR+PIK3CA | N/A | N/A | N/A | N/A |
Wang et al. [51] | EGFR+PIK3CA | Gefitinib | N/A | N/A | PR |
Klempner et al. [52] | EGFR+RET | Erlotinib | N/A | N/A | PR/PD |
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Gristina, V.; La Mantia, M.; Galvano, A.; Cutaia, S.; Barraco, N.; Castiglia, M.; Perez, A.; Bono, M.; Iacono, F.; Greco, M.; et al. Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma. J. Mol. Pathol. 2021, 2, 173-196. https://doi.org/10.3390/jmp2020016
Gristina V, La Mantia M, Galvano A, Cutaia S, Barraco N, Castiglia M, Perez A, Bono M, Iacono F, Greco M, et al. Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma. Journal of Molecular Pathology. 2021; 2(2):173-196. https://doi.org/10.3390/jmp2020016
Chicago/Turabian StyleGristina, Valerio, Maria La Mantia, Antonio Galvano, Sofia Cutaia, Nadia Barraco, Marta Castiglia, Alessandro Perez, Marco Bono, Federica Iacono, Martina Greco, and et al. 2021. "Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma" Journal of Molecular Pathology 2, no. 2: 173-196. https://doi.org/10.3390/jmp2020016