Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review
Abstract
:1. Introduction
2. Anti-Tumor Mechanism
3. Afatinib’s Effectiveness in Curing Various Uncommon EGFR Mutations
3.1. Major Uncommon Mutations (G719X/S768I/L861Q)
3.2. Exon 18 Mutations (Except G719X)
3.3. Uncommon Mutations in Exon 19
3.4. Exon 20 Insertions and T790M Mutations
3.5. Uncommon Exon 21 Mutations
3.6. Compound Mutations
3.7. Rare Mutations following Resistance to Osimertinib
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Study | n | Mutation | Tumor Staging | Therapy Line | Response | PFS (mos) (95% CI) | OS (mos) (95% CI) |
---|---|---|---|---|---|---|---|
Hao Y., 2022 [18] | 11 | E709A/G/K, E709-T710delinsD | IV | first or above | N/A | 13.5 | 17.1 |
Iwamoto Y., 2019 [19] | 1 | E709-T710delinsD | IV | sixth | PR | 7 | N.R. |
Ibrahim U., 2017 [20] | 1 | E709-T710delinsD | IV | first | PR | N.R. | N.R. |
An N., 2019 [21] | 1 | E709-T710delinsD | IIIA | second | PR | 11 | >21 |
Wei Y., 2021 [22] | 1 | E709-T710delinsD | IIB | first | PR | 23 | N.R. |
Study | n | Mutation | Tumor Staging | Therapy Line | ORR (%) | Response | PFS (mos) (95% CI) | OS (mos) (95% CI) |
---|---|---|---|---|---|---|---|---|
Liang S.K., 2019 [25] | 5 | L747S or L747P | IV | first | 80 | N/A | 11.97 (6.37–17.57) | 16.62 (3.05–30.19) |
Shan B.B., 2022 [24] | 1 | I740_K745dup | IV | second | 0 | SD | 13.4 | 21.3 |
Zhang L., 2022 [26] | 1 | E746_L747delinsIP | IV | fourth | 100 | PR | >6.5 | N.R. |
Kanbe M., 2022 [27] | 1 | L747V and 21 L858R | IV | sixth | 100 | PR | 12 | N.R. |
Fang Y.F., 2021 [28] | 1 | T751_I759delinsS | IV | second | 100 | PR | 9 | N.R. |
Study | n | Mutation | ORR (%) | TTF (mos) (95% CI) |
---|---|---|---|---|
Yang J.C., 2022 [15] | 42 | Overall | 33 | 9.1 (7.4–14.2) |
4 | A763_Y764insFQEA; A763_V765dup | 50 | 39.0 (8.2–39.0) | |
5 | A767_S768insSVA; _V769dup/ASV; insASVD | 0 | 3.7 (1.0–36.0) | |
3 | D770_N771insGL/SVD | 0 | 3.8 (3.0–20.1) | |
9 | H773_R776insYNPY; _V774dup/insH; dup | 0 | 24.0 (6.1–NE) | |
2 | M766delinsMATL; insASV | 100 | 12.9 (11.6–14.2) | |
7 | N771_H773dup; _772insPHGH; delinsKG; _P772insGY | 71 | 10.0 (5.2–NE) | |
5 | S768_D770dup | 0 | 8.5 (NE–NE) | |
7 | V769_770INSV; _D770insASV/GVV | 75 | 8.0 (1.2–14.3) |
Study | n | Mutation | Tumor Staging | Therapy Line | ORR (%) | Response | PFS (mos) (95% CI) |
---|---|---|---|---|---|---|---|
Zochbauer-Muller S., 2020 [33] | 1 | H773dup | N.R. | first | 0 | SD | >54 |
Lin L., 2020 [34] | 1 | N771delinsKG | IV | first | 100 | PR | 10 |
Chan R.T., 2018 [35] | 1 | A767_S768insSVA | IV | third | 0 | SD | 36 |
Cai Y., 2019 [37] | 1 | A767delinsASVD | IV | second | 0 | SD | 7.4 |
Urban L., 2021 [36] | 1 | H773_V774insNPH | IV | second | 100 | PR | >36 |
Oyamada Y., 2021 [38] | 1 | D770_N771insSVD | IV | fourth | 100 | PR | N/A |
van Veggel B., 2018 (with cetuximab) [39] | 4 | Overall | IV | second/ third | 75 | N/A | 5.4 (0.0–14.2) |
1 | S768_A770dup | second | 100 | PR | 17.6 | ||
1 | A771_H773dup | second | 100 | PR | 4.4 | ||
1 | H773dup | third | 0 | SD | 2.7 | ||
1 | A767_V769dup | third | 100 | PR | >6.4 |
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Jiang, Y.; Fang, X.; Xiang, Y.; Fang, T.; Liu, J.; Lu, K. Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review. Curr. Oncol. 2023, 30, 5337-5349. https://doi.org/10.3390/curroncol30060405
Jiang Y, Fang X, Xiang Y, Fang T, Liu J, Lu K. Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review. Current Oncology. 2023; 30(6):5337-5349. https://doi.org/10.3390/curroncol30060405
Chicago/Turabian StyleJiang, Yingying, Xiaoxu Fang, Yan Xiang, Tingwen Fang, Jingwen Liu, and Kaihua Lu. 2023. "Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review" Current Oncology 30, no. 6: 5337-5349. https://doi.org/10.3390/curroncol30060405
APA StyleJiang, Y., Fang, X., Xiang, Y., Fang, T., Liu, J., & Lu, K. (2023). Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review. Current Oncology, 30(6), 5337-5349. https://doi.org/10.3390/curroncol30060405