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. 2022 Jun;11(6):1027-1037.
doi: 10.21037/tlcr-22-376.

Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with stage IV non-small cell lung cancer: a retrospective study

Tian Tian #  1 , Min Yu #  1 , Yang Yu  1 , Ke Wang  2 , Panwen Tian  2 , Ziyue Luo  3 , Zhenyu Ding  4 , Ye Wang  2 , Youling Gong  1 , Jiang Zhu  1 , Bingwen Zou  1 , Terence T Sio  5 , Adelaide Alves  6 , Yongmei Liu  1 , Meijuan Huang  1 , You Lu  1
Affiliations

Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with stage IV non-small cell lung cancer: a retrospective study

Tian Tian et al. Transl Lung Cancer Res. 2022 Jun.

Abstract

Background: Although immune checkpoint inhibitors (ICIs) provide unprecedented survival improvement for patients with advanced non-small cell lung cancer (NSCLC), disease progression inevitably occurs. After ICIs failure, limited data exist on whether ICI-based treatment beyond progression (TBP) may be beneficial to advanced NSCLC. This retrospective study aimed to evaluate the efficacy of this treatment approach in advanced NSCLC and identify potential beneficial factors.

Methods: Patients with stage IV NSCLC who received ICI-based treatment after the failure of prior PD-1/PD-L1 inhibitor treatments (monotherapy or combination therapy) between January 2016 and July 2020 were enrolled. Their clinical characteristics and treatment procedures were collected, and the follow-up would be performed.

Results: A total of 204 patients were included. All patients had disease progression after prior immunotherapy, with 49.5% (101/204) of patients presenting with new metastasis lesions and the rest 50.5% (103/204) of patients' progression on originate lesions. Within the entire cohort, the median progression-free survival (PFS) and median overall survival (OS) of ICI-based TBP with prior immunotherapy were 5.0 months (95% CI: 4.5-5.5 months) and 15.7 months (95% CI: 14.7-16.8 months), respectively. The objective response rate (ORR) and disease control rate (DCR) were 9.3% and 74.0%, respectively. According to the multivariate analysis, ICI-based combination therapy [PFS: hazard ratio (HR), 0.48, 95% confidence interval (CI): 0.28-0.84, P=0.011] (OS: HR, 0.44, 95% CI: 0.23-0.85, P=0.014), not having targetable gene alterations (PFS: HR, 0.56, 95% CI: 0.40-0.79, P=0.001) (OS: HR, 0.57, 95% CI: 0.37-0.87, P=0.009), and good response to prior immunotherapy (PFS: HR, 0.36, 95% CI: 0.24-0.53, P<0.0001) (OS: HR, 0.31, 95% CI: 0.19-0.52, P<0.0001) were independently associated with improved PFS and OS. Moreover, disease progression due to appearances of new metastasis (OS: HR, 0.56, 95% CI: 0.37-0.84, P=0.005) was only associated with better OS.

Conclusions: While the ORR in patients with advanced NSCLC receiving ICI-based TBP with prior immunotherapy was limited, the DCR was relatively high in our study which is encouraging. ICI-based treatment strategy may be a reasonable option for patients who progressed from prior immunotherapy. Further prospective studies on larger sample size are warranted.

Keywords: Non-small cell lung cancer (NSCLC); immune checkpoint inhibitors (ICIs); immunotherapy; metastatic; treatment beyond prior immunotherapy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-376/coif). TTS reports that he provides strategic and scientific recommendations as a member of the Advisory Board and speaker for Novocure, Inc., and also as a member of the Advisory Board to Galera Therapeutics, which are not in any way associated with the content or disease site as presented in this manuscript. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The flow chart of the screening procedure. NSCLC, non-small cell lung cancer; ICI, immune checkpoint inhibitor.
Figure 2
Figure 2
Kaplan-Meier curves of PFS (A) and OS (B) of patients with advanced NSCLC who received ICI-based treatment beyond progression with prior immunotherapy. mPFS, median progression-free survival; mOS, median overall survival; NSCLC, non-small cell lung cancer; ICI, immune checkpoint inhibitor.
Figure 3
Figure 3
Kaplan-Meier curves of PFS and OS by the response to prior immunotherapy. (A,B) The patients who responded well to prior immunotherapy (CR/PR) had better PFS and OS than the patients who response not well (SD/PD) (mPFS 7.3 vs. 4.3 months, P<0.0001; mOS 22.8 vs. 15.7 months, P<0.0001). mPFS, median progression-free survival; mOS, median overall survival; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.
Figure 4
Figure 4
The objective response rate of the following immunotherapy in patients with different best response to prior immunotherapy [the first column (left) indicates the efficacy of the first round of immunotherapy, while the second column (right) indicates the efficacy of the second round of ICI treatment that was given after prior immunotherapy]. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ICI, immune checkpoint inhibitor.
Figure 5
Figure 5
Kaplan-Meier curves of PFS and OS by treatment strategy of ICI treatment beyond progression with prior immunotherapy. (A,B) The patients who received ICI-based combination therapy achieved more favorable PFS and OS than those of patients who received ICI monotherapy (mPFS 5.1 vs. 3.3 months, P=0.001; mOS 18.4 vs. 13.7 months, P=0.01). mPFS, median progression-free survival; mOS, median overall survival; ICI, immune checkpoint inhibitor.
Figure 6
Figure 6
Kaplan-Meier curves of PFS and OS by driver gene alteration status. (A,B) The patients without gene alterations had better PFS and OS than those of patients with gene alterations (mPFS 5.5 vs. 3.5 months, P=0.001; mOS 16.1 vs. 13.9 months, P=0.012). mPFS, median progression-free survival; mOS, median overall survival.
Figure 7
Figure 7
Kaplan-Meier curves of the subgroup analysis regarding PFS and OS of whether combined with chemotherapy among the combination treatment groups. (A,B) The chemotherapy cohort had better PFS and OS than those of the non-chemotherapy cohort (mPFS 5.3 vs. 4.6 months, P=0.13; mOS 16.5 vs. 15.2 months, P=0.12). mPFS, median progression-free survival; mOS, median overall survival; ICI, immune checkpoint inhibitor.
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References

    1. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016;375:1823-33. 10.1056/NEJMoa1606774 - DOI - PubMed
    1. Gadgeel S, Rodríguez-Abreu D, Speranza G, et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol 2020;38:1505-17. 10.1200/JCO.19.03136 - DOI - PubMed
    1. Doroshow DB, Sanmamed MF, Hastings K, et al. Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes. Clin Cancer Res 2019;25:4592-602. 10.1158/1078-0432.CCR-18-1538 - DOI - PMC - PubMed
    1. Horvath L, Thienpont B, Zhao L, et al. Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook. Mol Cancer 2020;19:141. 10.1186/s12943-020-01260-z - DOI - PMC - PubMed
    1. Bersanelli M, Buti S, Giannarelli D, et al. Chemotherapy in non-small cell lung cancer patients after prior immunotherapy: The multicenter retrospective CLARITY study. Lung Cancer 2020;150:123-31. 10.1016/j.lungcan.2020.10.008 - DOI - PubMed