Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 23:11:739090.
doi: 10.3389/fonc.2021.739090. eCollection 2021.

Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Tian Tian  1 , Min Yu  1 , Juan Li  2 , Maoqiong Jiang  3 , Daiyuan Ma  4 , Shubin Tang  5 , Zhiyu Lin  6 , Lin Chen  1 , Youling Gong  1 , Jiang Zhu  1 , Qiang Zhou  7 , Meijuan Huang  1 , You Lu  1
Affiliations

Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Tian Tian et al. Front Oncol. .

Abstract

Background: Data on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.

Materials and methods: Relevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.

Results: A total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).

Conclusions: Taken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.

Keywords: epidermal growth factor receptor; immune checkpoint inhibitor; non–small cell lung cancer; resistance; tyrosine kinase inhibitor.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for progression-free survival and overall survival of patients with EGFR-mutant NSCLC (n = 122). The median PFS and OS were 5.0 months and 14.4 months, respectively.
Figure 2
Figure 2
Kaplan–Meier curves of progression-free survival and overall survival of patients who received ICI therapy at different lines of treatment. The patients who were administered front-line ICI exhibited superior survival benefits than those who received ICI as later line after progression on TKI (mPFS 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS 15.1 months vs. 8.4 months, respectively, P < 0.0001).
Figure 3
Figure 3
Kaplan–Meier curves of progression-free survival and overall survival of patients who received ICI-based combination therapy versus ICI monotherapy. The efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS 5.0months vs. 2.2 months, P = 0.002, mOS 14.4 months vs. 7.0 months, P = 0.001).
Figure 4
Figure 4
Kaplan–Meier curves of progression-free survival and overall survival of patients with differential PD-L1 expression. A significant PFS benefit was observed in patients with strong positive PD-L1 expression (TPS ≥ 50%) compared with that in patients with a lower PD-L1 expression (TPS < 50%) (7.5 months vs 3.0 months, respectively, P = 0.001), but the difference in OS was not statistically significant.
Figure 5
Figure 5
Kaplan–Meier curves of progression-free survival and overall survival of patients with differential mutation type. A significant PFS benefit was observed in patients with L858R compared with that in patients with 19Del (6.1 months vs. 3.8 months, respectively, P = 0.002), but the difference in OS was not statistically significant.
See this image and copyright information in PMC

References

    1. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, et al. . EGFR Mutation and Resistance of Non- Small- Cell Lung Cancer to Gefitinib. N Engl J Med (2005) 352(8):786–92. doi: 10.1056/NEJMoa044238 - DOI - PubMed
    1. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. . Erlotinib Versus Chemotherapy as First-Line Treatment for Patients With Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer (OPTIMAL, CTONG-0802): A Multicentre, Open- Label, Randomised, Phase 3 Study. Lancet Oncol (2011) 12:735–42. doi: 10.1016/S1470-2045(11)70184-X - DOI - PubMed
    1. Ohashi K, Maruvka YE, Michor F, Pao W. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor- Resistant Disease. J Clin Oncol (2013) 31:1070–80. doi: 10.1200/JCO.2012.43.3912 - DOI - PMC - PubMed
    1. Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, et al. . Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med (2017) 376(7):629–40. doi: 10.1056/NEJMoa1612674 - DOI - PMC - PubMed
    1. Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, et al. . Gefitinib Plus Chemotherapy Versus Placebo Plus Chemotherapy in EGFR-Mutation-Positive Non-Small-Cell Lung Cancer After Progression on First-Line Gefitinib (IMPRESS): A Phase 3 Randomised Trial. Lancet Oncol (2015) 16(8):990–8. doi: 10.1016/S1470-2045(15)00121-7 - DOI - PubMed