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. 2022 Aug;11(8):1555-1566.
doi: 10.21037/tlcr-22-140.

Safety and efficacy of retreatment with immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis

Zijing Cai  1 , Ping Zhan  2 , Yong Song  2 , Hongbing Liu  2 , Tangfeng Lv  1   2
Affiliations

Safety and efficacy of retreatment with immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis

Zijing Cai et al. Transl Lung Cancer Res. 2022 Aug.

Abstract

Background: Retreatment with immune checkpoint inhibitors (ICIs) might be a subsequent therapeutic option for patients with non-small cell lung cancer (NSCLC) who discontinued initial ICIs treatment because of disease progression, immune-related adverse events (irAEs) or completion of a fixed course, yet little evidence exists on the safety and efficacy of ICIs retreatment to support this strategy.

Methods: We searched PubMed, Web of Science, Embase, Cochrane and major meeting libraries for articles about ICIs retreatment in NSCLC for systematic review and meta-analysis. The outcomes included objective response rate (ORR) and disease control rate (DCR) for efficacy and the incidence of all-grade and high-grade irAEs for safety. ICIs rechallenge implies retreatment that can be applied to patients who progressed, while ICIs resumption refers to retreatment for patients who discontinued prior treatment due to an irAE or completion of a fixed course of immunotherapy.

Results: Eighteen studies were enrolled in our analysis. The pooled ORR and DCR of ICIs retreatment were respectively 20% and 54%. ICIs retreatment was associated with a decrease in ORR and DCR compared to prior ICIs treatment (ORR: OR, 0.29, 95% CI: 0.14, 0.63, P=0.002; DCR: OR, 0.53, 95% CI: 0.28-0.99, P=0.05). The pooled ORR and DCR of ICIs rechallenge were 8% and 39%. ICIs rechallenge showed a lower ORR compared with initial ICIs treatment (P<0.05). ICIs resumption presented an ORR of 34% and a DCR of 71%, showing no significant difference in ORR and DCR compared with initial ICIs treatment (P>0.05). Retreated with the same type of ICIs as before showed no difference in ORR and DCR (P>0.05), while with different ICIs was associated with a decrease in ORR and DCR in contrast to initial treatment (P<0.05). The pooled incidence of all-grade and high-grade irAEs after ICIs retreatment in patients with NSCLC were separately 41% and 13% which showed a similar incidence compared with initial ICIs treatment (P>0.05).

Discussion: Retreatment with ICIs is feasible for patients with NSCLC in consideration of its encouraging efficacy and tolerable safety, especially in resumption with ICIs. When it comes to ICIs rechallenge, it is necessary to accurately identify the potential targeted beneficiary population. More large-scale prospective studies are warranted to confirm our discoveries. More attention could be paid to further exploring the efficacy and safety of retreatment concurrently with ICIs and chemotherapy.

Keywords: Non-small cell lung cancer (NSCLC); immune checkpoint inhibitors (ICIs); rechallenge; resumption; retreatment; safety and efficacy.

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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-22-140/coif). YS serves as an Editor-in-Chief of Translational Lung Cancer Research from September 2014 to August 2022. TL serves as an unpaid Associate Editor-in-Chief of Translational Lung Cancer Research. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
PRISMA 2020 flow diagram. “n” represents the numbers of studies. ICI, immune checkpoint inhibitor.
Figure 2
Figure 2
Subgroup analyses of the association between the efficacy of ICIs retreatment and the reason for interruption of initial ICIs. (A) the ORR of ICIs rechallenge; (B) the DCR of ICIs rechallenge; (C) the ORR of ICIs resumption; (D) the DCR of ICIs resumption. ICIs rechallenge was defined as retreatment that can be applied to patients who progressed during treatment or within 12 weeks of termination of immunotherapy. ICIs resumption was defined as retreatment of a patient who previously discontinued immunotherapy because of an irAE or completion of a fixed course of immunotherapy. ORR, objective response rate; DCR, disease control rate; ICIs, immune checkpoint inhibitors; CI, confidence interval; M-H, Mantel-Haenszel model; irAEs, immune-related adverse events.
Figure 3
Figure 3
Forest plot of the association between ICIs retreatment and the incidence of irAEs. (A) All-grade irAEs (P>0.05); (B) high-grade irAEs (P>0.05). Grade ≥3 was defined as high-grade irAEs. CI, confidence interval; M-H, Mantel-Haenszel model; ICI, immune checkpoint inhibitor; irAEs, immune-related adverse events.
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