Abstract
Purpose
Drug resistance inevitably occurs despite the encouraging results of immunotherapy. This study attempted to investigate immunotherapy rechallenge treatment regimens and factors associated with outcomes in patients with non-small cell lung cancer (NSCLC) according to resistance status.
Methods
A retrospective study was conducted on patients with advanced NSCLC who received immune checkpoint inhibitor (ICI) monotherapy and immune rechallenge between March 2016 and December 2022. Primary resistance (RR) was defined by an absence of response after treatment administered for less than 6 months before progression. Acquired resistance (AR) was defined as a response to immunotherapy treatment administered for more than 6 months before progression. Disease progression in as many as three lesions was defined as systemic progression, whereas disease progression in fewer than three lesions was defined as oligo-progression.
Results
Of 40 patients, 18 (45%) had primary resistance, and 22 (55%) developed AR. Overall survival (OS) was not reached. A significant difference in progression-free survival (PFS) was observed in individuals rechallenged with ICIs after AR and RR (7.0 months vs. 2.1 months, P = 0.003). Patients receiving interval treatment before rechallenge achieved longer PFS than those who did not (6.2 months vs. 4.0 months, P = 0.027). Multivariate analysis demonstrated that systemic progression was a risk factor significantly associated with PFS after ICI rechallenge (P = 0.006). After AR, ICI rechallenge prolonged the duration of PFS if patients developed oligo-progression (5.4 months vs. 1.1 months, P < 0.001).
Conclusion
ICI rechallenge is likely to be an option for patients with oligo-progression during rechallenge, particularly after AR.
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Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors appreciate all patients for their cooperation and participation. In addition, we are thankful to all research staff and co-investigators involved in this study.
Funding
The study was supported by the Medical Scientific Research Foundation of Zhejiang Province (No.2022KY653), and sponsored by Zhejiang provincial program for the Cultivation of High-Level Innovative Health Talents (to Zhengbo Song).
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ZS designed and supervised the research. MX, YH and ZS conducted the follow-up, data collection and correlative analysis. ZS provided support in data analysis and use of software. MX and YH provided data analysis. All authors were involved in manuscript preparation and approved the final manuscript.
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Approval of the study protocol was obtained from Zhejiang Cancer Hospital Institutional Review Board Committee (approval number: IRB-2022-187). Individual consent for this retrospective analysis was waived.
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Supplementary file1 Supplementary Fig.1 Kaplan–Meier curves of PFS for the initial immunotherapy of the entire group. The median PFS of patients in the entire group was 5.2 (95%CI: 3.6 to 6.8) months when treated with the initial immune monotherapy (PDF 4 KB)
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Xu, M., Hao, Y., Shi, Z. et al. Efficacy of rechallenge immunotherapy after immune monotherapy resistance in patients with advanced non-small cell lung cancer. J Cancer Res Clin Oncol 149, 17987–17995 (2023). https://doi.org/10.1007/s00432-023-05490-8
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DOI: https://doi.org/10.1007/s00432-023-05490-8