EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Lung Cancer and EGFR Mutations
3. TKIs as Neoadjuvant Treatment
4. TKI as Adjuvant Treatment
5. Impact of EGFR Mutation and Co-Mutations
6. Safety
7. Cost Effectiveness and Accessibility
8. Discussion
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name, Author Year | Design | Patients | Stage | HR (p) | N+ Down-Staging (p) | ||||
---|---|---|---|---|---|---|---|---|---|
ORR | OpR | PRR | PFS | OS | |||||
Chen 2018 [24] | Phase II Erlotinib vs. chemo (P + C) | EGFRm (86) | IIIA | 1.53 (<0.05) | 1.08 (>0.05) | 1.55 (<0.05) | NA | NA | NA |
CTONG 1103, Zhong 2019 [25] | Phase II Erlotinib vs. chemo (G + C) | EGFRm (72) | IIIA N2 | 2.26 (0.092) | NA, 83.8% vs. 68.6% (0.129) † | NA, 9.7% vs. 0% † | 0.39 (<0.001) | 0.77 (0.417) | 10.8% vs. 2.9% (0.185) † |
Zhong 2015 [26] | Phase II Erlotinib vs. chemo (G + C) * | EGFRm (12) EGFRw (12) | IIIA N2 | NA, 58.3% vs. 25% (0.18) † | NA, 6/12 vs. 7/12 † | NA | 2.26 (0.071) | 1.79 (0.201) | 25% vs. 25% (1) † |
Xiong 2019 [27] | Phase II Erlotinib vs. chemo * | EGFRm (15) EGFRw (16) | IIIA | NA, 67% vs. 19% † | NA, 12/15 vs. 8/16 † | NA, 67% vs. 38% † | NA, 12.1 vs. 11 †,‡ | NA, 51 vs. 20.9 (0.12) †,‡ | NA |
Ning 2019 [28] | Erlotinib vs. chemo (P + C) * | EGFRm (53) EGFRw (53) | IIIA | NA, 35/53 vs. 22/53 † | NA, 46/53 vs. 43/53 † | NA | NA | NA | NA |
Name, Trial Number | Tested Drug | Treatment Plan | Adjuvant TKI | Primary Outcome | Stage | n |
---|---|---|---|---|---|---|
NCT04685070 [33] | Almonertinib | 8–16 weeks | up to 40 weeks | ORR | Stage III | 56 |
NCT04201756 [34] | Afatinib | 8–16 weeks | 1 year | ORR | Stage III | 47 |
NCT03749213 [35] | Icotinib | 8 weeks | 2 years | ORR | IIIA N2 | 36 |
NCT03349203 [36] | Icotinib | 8 weeks | 2 years | ORR | IIIB or oligometastasis | 60 |
Neolpower, NCT05104788 [37] | Icotinib + chemo | 12 weeks | NA | MPR | IIA−IIIB | 27 |
NCT02820116 [38] | Icotinib | 8 weeks | 2 years | Complete resection rate | IIIA−IIIB | 67 |
NOCE01, NCT05011487 [39] | Osimertinib + chemo | 60 days | NA | Complete lymph node clearance rate * | IIIA−IIIB N2 | 30 |
NCT03433469 [40] | Osimertinib | 4–10 weeks | No | MPR | I−IIIA | 27 |
ASCENT, NCT01553942 [41] | Afatinib + radio + chemo | 8 weeks | 2 years | Response rate | IIIA | 30 |
Name, Author Year | Design | EGFR Status (n) | Stages | HR DFS (p) | HR OS (p) |
---|---|---|---|---|---|
Tsuboi 2005 [42] | Phase III Gefitinib vs. placebo | UP (38) | IB−IIIA | NA | NA |
BR19, Goss 2013 [52] | Phase III Gefitinib vs. placebo | UP (503) EGFRm (15) | IB−IIIA | 1.84 (0.395) | 3.16 (0.15) |
Li 2014 [46] | Phase II Chemo (P + C) + Gefitinib vs. chemo alone | EGFRm (60) | IIIA (N2) (5th TNM) | 0.37 (0.014) | 0.37 (0.076) |
Feng 2015 [48] | Phase II chemo + Icotinib vs. chemo alone | EGFRm (39) | IB−IIIA | NA, 21 vs. 16 (0.122) | NA |
RADIANT, Kelly 2015 [50] | Phase III Erlotinib vs. placebo | EGFRexp (973) EGFRm (161) | IB−IIA (6th TNM) | 0.61 | 1.09 (0.815) |
EVAN, Yue 2018 [49] | Phase II Erlotinib vs. chemo (V + P) | EFGRm (102) | IIIA | 0.268 (<0.0001) | 0.165 (0.0013) |
ADJUVANT, Zhong 2018 [53] | Phase III Gefitinib vs. chemo (V + P) | EGFRm (222) | II−IIIA (N1-2) | 0.51 (0.001) | 0.92 (0.674) |
ADAURA, Wu 2020 [1] | Phase III Osimertinib vs. placebo | EGFRm (682) | IB−IIIA (7th TNM) | 0.2 (<0.001) | NA |
IMPACT, Tada 2021 [51] | Phase III Gefitinib vs. chemo (V + P) | EGFRm (234) | II−IIIA | 0.92 (0.63) | 1.03 (0.89) |
EVIDENCE, He 2021 [54] | Phase III Icotinib vs. chemo (V + P) | EGFRm (322) | II−IIIA (7th TNM) | 0.36 (<0.0001) | 0.75 (>0.05) |
* SELECT, Pennel 2019 [47] | Phase II Erltonib after chemo (comparison to historical data) | EGFRm (100) | IA−IIIA (7th TNM) | NA, 88% vs. 76% (0.047) † | NA |
Name, Trial Number | Design | Setting | Treatment Arms | Primary Outcome | Stages | n |
---|---|---|---|---|---|---|
NeoADAURA, NCT04351555 [32] | Phase III, randomized, controlled, multi-center, 3-arm trial | Neo- adjuvant | Osimertinib + chemo vs. placebo + chemo vs. Osimertinib | MPR | II−IIIB N2 | 328 |
ADAURA2, NCT05120349 [64] | Phase III, randomized, controlled, multi-center, international, 2-arm trial | Adjuvant | Osimertinib vs. placebo | DFS | IA2, IA3 | 380 |
ICTAN, NCT01996098 [65] | Phase III, randomized, open label, multi-center, 3-arm trial | Adjuvant, after chemo | Icotinib 6 months vs. Icotinib 12 months vs. no treatment | DFS | IIA −IIIA | 318 |
APEX, NCT04762459 [66] | Phase III, randomized, open label, multi-center, 3-arm trial | Adjuvant | Almonertinib vs. Almonertinib + chemo vs. chemo | DFS | II −IIIA | 606 |
ALCHEMIST, NCT02193282 [63] | Phase III, randomized, controlled, nationwide, multi-center, 4-arm trial | Adjuvant | Erlotinib (blinded) vs. placebo (blinded) vs. Erlotinib (unblinded) vs. placebo (unblinded) | OS | IB (≥4 cm) −IIIA | 450 |
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Cansouline, X.; Lipan, B.; Sizaret, D.; Tallet, A.; Vandier, C.; Carmier, D.; Legras, A. EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors? Cancers 2022, 14, 2257. https://doi.org/10.3390/cancers14092257
Cansouline X, Lipan B, Sizaret D, Tallet A, Vandier C, Carmier D, Legras A. EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors? Cancers. 2022; 14(9):2257. https://doi.org/10.3390/cancers14092257
Chicago/Turabian StyleCansouline, Xavier, Béatrice Lipan, Damien Sizaret, Anne Tallet, Christophe Vandier, Delphine Carmier, and Antoine Legras. 2022. "EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors?" Cancers 14, no. 9: 2257. https://doi.org/10.3390/cancers14092257