The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

Fujisaki, Toshiya; Watanabe, Satoshi; Ota, Takayo; Kushiro, Kohei; Sato, Yusuke; Takahashi, Miho; Ohtsubo, Aya; Shoji, Shuichi; Nozaki, Kohei; Ichikawa, Kosuke; Hokari, Satoshi; Kondo, Rie; Miyabayashi, Takao; Abe, Tetsuya; Miura, Satoru; Tanaka, Hiroshi; Okajima, Masaaki; Tomita, Masaki; Matsumoto, Naoya; Ishida, Takashi; Iwashima, Akira; Sato, Kazuhiro; Yoshizawa, Hirohisa; Aoki, Nobumasa; Hayashi, Masachika; Ohshima, Yasuyoshi; Koya, Toshiyuki; Kikuchi, Toshiaki

doi:10.3389/fonc.2021.704475

Cited by 15 publications

(10 citation statements)

References 26 publications

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“…36 In some patients, it is feasible to consider ICI rechallenge after irAE remission, even if same or new toxicities occur, as most secondary irAEs are not more severe than the initial irAEs and could be manageable. 37,38 In our study, we found that the incidence of the second irAE in patients who underwent ICI rechallenge was 44.8% (13/29), which aligns with the incidence reported in previous studies. 39 Patients with initial irAEs of gastrointestinal toxicity (2/2), cardiovascular toxicity (1/1), and pneumonitis (5/10) were more prone to developing secondary irAEs.…”

Section: Discussionsupporting

confidence: 91%

Different associations between organ-specific immune-related adverse event and survival in non-small cell lung cancer patients treated with programmed death-1 inhibitors-based combination therapy

Chen,

Shi,

Ding

et al. 2023

Ther Adv Med Oncol

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Background: The profile of immune-related adverse events (irAEs) due to programmed death-1 (PD-1) inhibitors-based combination therapy in advanced non-small cell lung cancer (NSCLC) and its relationship with survival have not been fully described. Objective: Designed to capture the spectrum of irAEs and explore the association between irAEs and clinical outcomes in patients with NSCLC. Design: This retrospective single-center study included patients with advanced NSCLC treated with PD-1 inhibitors (mainly in combination with chemotherapy) at Jiangsu Cancer Hospital. Methods: The relationship between irAEs and survival was explored using landmark analysis and time-dependent Cox regression. The subgroup analyses focused on investigating the effects of organ-specific irAE, irAE grade, and steroid dose used to treat irAE. Results: This study included 301 patients, 199 of whom received PD-1 inhibitors plus chemotherapy. The most common irAEs were skin toxicity (19.3%), endocrinopathy (21.3%), and pneumonitis (17.6%). In the entire cohort, the median progression-free survival (PFS) for patients developing and not developing irAE was 12.3 and 10.7 months ( p < 0.001), and the median overall survival (OS) was 23.5 months and 20.1 months ( p = 0.137), respectively. Subgroup analyses indicated that grade 3 or higher irAE, high steroid dose, and immune-related pneumonitis were detrimental to OS, whereas skin toxicity was beneficial to survival. These findings were further corroborated by both landmark analyses and Cox regression models conducted over four time points (1, 3, 6, and 12 months). Conclusion: In the real world, NSCLC patients receiving PD-1 inhibitor-based combination therapy (particularly combined with chemotherapy) experience longer PFS with irAE, though not necessarily OS. Immune-related skin toxicity is associated with a better prognosis, whereas pneumonitis grade ⩾3 irAE and high steroid dose compromise survival. Clinicians should remain cognizant of the organ-specific manifestations of irAE and take proactive measures to mitigate the progression of irAE.

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Section: Discussionsupporting

confidence: 91%

Different associations between organ-specific immune-related adverse event and survival in non-small cell lung cancer patients treated with programmed death-1 inhibitors-based combination therapy

Chen,

Shi,

Ding

et al. 2023

Ther Adv Med Oncol

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“…Sixteen studies (8,9,(17)(18)(19)(20)(21)(23)(24)(25)(26)(27)(28)(29)31,32) were enrolled in the analysis of efficacy of ICIs retreatment. The pooled ORR and DCR of ICIs retreatment were respectively 20% and 54% (Table 2).…”

Section: Efficacymentioning

confidence: 99%

“…Nine studies (17,21,23,(25)(26)(27)(28)(29)32) were involved in the analysis of safety. The occurrence rate of all-grade and high-grade irAEs were 41% and 13% separately (Table 2).…”

Section: Safetymentioning

confidence: 99%

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

Cai¹,

Zhan²,

Song³

et al. 2022

Transl Lung Cancer Res

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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 for 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.

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“…A narrow definition is the resumption of ICI after irAEs improve in patients who stopped treatment due to irAEs (28). A more general definition is the resumption of ICI in patients who stopped treatment for any cause, including the adjustment of specific drugs (29,30). Research has mainly focused on the narrow definition of ICI rechallenge.…”

Section: Discussionmentioning

confidence: 99%

Efficacy, prognosis and safety analysis of anti-PD-1/PD-L1 inhibitor rechallenge in advanced lung cancer patients: a cohort study

Yang¹,

Ran²,

Zhou³

et al. 2022

Transl Lung Cancer Res

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Background: The rechallenge of immune checkpoint inhibitors (ICI) is now an optional strategy for patients who discontinued ICI due to immune-related adverse events (irAEs) or disease progression.However, little data is available for the prognosis and prognostic factors of patients receiving ICI rechallenge treatment in advanced lung cancer patients. Our study aimed to explore the efficacy, prognosis and safety of patients who received anti-programmed cell death-1/programmed cell death ligand 1 (anti-PD-1/PD-L1) inhibitor rechallenge.Methods: In our retrospective cohort study, data of advanced lung cancer patients who received anti-PD-1/ PD-L1 inhibitor and discontinued due to irAEs or disease progression were collected from December 2016 to August 2021. Enrolled patients were categorized into two groups: rechallenge group (R group) and nonrechallenge group (NR group). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety data were analyzed. Cox model and subgroup analysis were analyzed according to baseline characteristics, ICI type, the reason for discontinuing ICI, etc. According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), evaluation was performed routinely every 6-8 weeks after initiating treatment with the PD-1/PD-L1 inhibitor. The last follow-up in the study was on September 20, 2021.Results: Eighty-one patients who met our inclusion criteria were enrolled. In the whole cohort, the R group achieved better OS than the NR group [hazard ratio (HR) =0.176; 95% confidence interval (CI): 0.065-0.477; P=0.001). In the irAEs group, the survival analyses showed a trend toward improved OS in the rechallenge subgroup (HR =0.287; 95% CI: 0.081-1.025; P=0.055), and a promising DCR of 75% after an ICI rechallenge. Additionally, the exploration of safety outcomes indicated an acceptable recurrence rate (22.5%) of irAEs and an early onset of irAEs after an ICI rechallenge. In the disease progression group, the rechallenge subgroup did not improve OS (HR =0.214; 95% CI: 0.027-1.695; P=0.144), and the DCR of the rechallenge subgroup was 40% after ICI rechallenge.Conclusions: ICI rechallenge might be an attractive option for patients who discontinue treatment due to irAEs. For patients with disease progression, further research should be conducted. The recurrence of irAEs and their early onset during the second round of ICI should be considered.

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The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

Cited by 15 publications

References 26 publications

Different associations between organ-specific immune-related adverse event and survival in non-small cell lung cancer patients treated with programmed death-1 inhibitors-based combination therapy

Different associations between organ-specific immune-related adverse event and survival in non-small cell lung cancer patients treated with programmed death-1 inhibitors-based combination therapy

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

Efficacy, prognosis and safety analysis of anti-PD-1/PD-L1 inhibitor rechallenge in advanced lung cancer patients: a cohort study

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