Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

Yin, Tianwen; Zhao, Kaikai; J, Yu; Teng, Feifei

doi:10.1007/s00432-021-03849-3

Cited by 13 publications

(14 citation statements)

References 33 publications

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“…After excluding 139 studies because the article type was not suitable for inclusion (including 13 case studies, 4 meta-analyses, 13 single-arm studies, 17 studies on other tumor types, 22 conference papers with abstracts only, 12 phase I studies, 15 ongoing studies, 42 reviews, and 1 comment), 3 RCTs and 12 NRCTs remained. A total of 15 clinical studies were reported in 16 publications ( Figure 1 ) ( Kataoka et al, 2017 ; Shaverdian et al, 2017 ; Tamiya et al, 2017 ; Fiorica et al, 2018 ; Theelen et al, 2019 ; Welsh et al, 2020 ; Hosokawa et al, 2021 ; Metro et al, 2021 ; Samuel et al, 2021 ; Sheng et al, 2021 ; Theelen et al, 2021 ; Öjlert Å et al, 2021 ; Guo et al, 2022 ; Qiang et al, 2022 ; Schoenfeld et al, 2022 ; Wang et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…The RT targets for three RCTs and five NRCTs were extracranial nonbrain metastases ( Tamiya et al, 2017 ; Fiorica et al, 2018 ; Theelen et al, 2019 ; Welsh et al, 2020 ; Hosokawa et al, 2021 ; Öjlert Å et al, 2021 ; Qiang et al, 2022 ; Schoenfeld et al, 2022 ). Three nonrandomized controlled studies included extracranial nonbrain metastases and intracranial brain metastases ( Shaverdian et al, 2017 ; Samuel et al, 2021 ; Wang et al, 2022 ). In three nonrandomized controlled studies, the RT targets included only brain metastases ( Metro et al, 2021 ; Sheng et al, 2021 ; Guo et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis

Liu

Chang

et al. 2023

Front. Pharmacol.

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Background and purpose: Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes. Furthermore, the adverse events rate was evaluated.Methods and materials: Pubmed, Embase, and Cochrane Library were searched using the keywords “radiotherapy,” “immune checkpoint inhibitors,” and “non-small cell lung cancer” from the date of inception to 2 May 2022. Randomized controlled trials (RCTs) and nonRCTs (NRCTs) comparing the efficacy and safety of RT combined with ICIs versus ICIs alone in metastatic NSCLC were assessed. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were abscopal response rate (ARR), abscopal control rate (ACR), adverse events rate, and pneumonia rate. The analyses were conducted using the Mantel–Haenszel fixed-effects or random-effects model. The I2 statistic was used to determine heterogeneity, whereas funnel plots and Egger’s test were used to assess publication bias.Results: In 15 clinical studies, 713 patients received RT combined with ICIs and 1,275 patients received only ICIs. With regard to PFS and OS, the hazard ratios of RT combined with ICIs were 0.79 (0.70, 0.89) and 0.72 (0.63, 0.82), respectively. In terms of ARR and ACR, the odds ratios (ORs) of RT combined with ICIs were 1.94 (1.19, 3.17) and 1.79 (1.08, 2.97), respectively. Subgroup analyses based on study type (RCT/NRCT), RT target (intracranial/extracranial), number of RT sites (single site), previous ICI resistance (yes/no), and sequencing of RT and ICIs (concurrent/post-RT ICIs) revealed that the addition of RT significantly prolonged PFS and OS. However, subgroup analyses based on radiation dose/fractionation indicated that the addition of hypofractionated RT significantly prolonged OS but not PFS. When grouped according to the level of PD-L1 expression, the addition of RT prolonged PFS only in patients who were PD-L1-negative. Furthermore, subgroup analyses of ARR and ACR signified that the combination therapy resulted in better local control of lesions outside the irradiation field in the hypofractionated RT, extracranial RT, and ICI-naïve subgroups. In terms of adverse events, the addition of RT did not significantly increase the adverse events rate but was associated with a higher pneumonia rate [OR values were 1.24 (0.92, 1.67) and 1.76 (1.12, 2.77), respectively].Conclusion: Meta-analysis of existing data suggests that the addition of RT can significantly prolong PFS and OS in patients with metastatic NSCLC receiving ICIs. In addition to lesions in the irradiation field, RT can improve the local control rate of lesions outside the irradiation field via immune activation. Combination therapy does not increase the overall risk of adverse reactions, except for pneumonia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis

Liu

Chang

et al. 2023

Front. Pharmacol.

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“…Regarding lung cancer studies, LCT-related adverse events were relatively more frequent when compared to other primaries, with grade 3 or higher rates ranging from 8% to 28.6%. Three studies reported the possibility of excessive grade 3 or higher adverse events related to LCT [ 28 , 35 , 67 ]. Grade 5 adverse event, potentially related to the LCT, occurred in three cases among seven lung cancer studies (3 of 281, 1.07%).…”

Section: Resultsmentioning

confidence: 99%

“… Forest plots of pooled analyses regarding progression-free survival, including all studies (A), studies with reliable comparability (B), and randomized controlled trials (C) [ 6 – 8 , 20 – 22 , 25 – 28 , 31 – 33 , 35 , 36 , 38 , 39 , 42 , 43 , 46 – 48 , 50 , 52 – 54 , 56 , 58 – 60 , 62 – 64 , 66 , 67 , 69 – 71 , 73 ]. HCC, hepatocellular carcinoma; H&N, head and neck; LCT, local consolidative therapy; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; SCLC, small cell lung cancer; 5ySSFS, 5-year second-line systemic therapy free survival.…”

Section: Figmentioning

confidence: 99%

Role of Local Treatment for Oligometastasis: A Comparability Based Meta-Analysis

et al. 2022

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We intend to investigate the oncological efficacy and feasibility of local consolidative therapy (LCT) through a meta-analysis method. Materials and MethodsFour databases including Pubmed, Medline, Embase, and Cochrane library were searched.Target studies are controlled trials comparing outcomes of LCT versus a control group. Primary endpoints are overall survival (OS) and progression-free survival (PFS). ResultsA total of 54 studies involving 7,242 patients were included. Pooled analyses showed that the LCT arm could achieve improved OS with pooled odds ratio of 2.896 (95% CI [confidence interval]: 2.377-3.528, p<0.001). Regarding PFS, pooled analyses showed pooled odds ratio of 3.045 (95% CI: 2.356-3.937, p<0.001) in favor of the LCT arm. In the subgroup analyses including the studies with reliable comparability (e.g. randomized studies or intentionally matched studies without significant favorable prognosticator in LCT arms), pooled odds ratio was 2.548 (95% CI: 1.808-3.591, p<0.001) favoring the LCT arm regarding OS. Regarding PFS, pooled OR was 2.656 (95% CI: 1.713-4.120, p<0.001) which also favored the LCT arm.Subgroup analyses limited to the randomized controlled trials (RCT) were also performed and pooled odds ratios on OS and PFS were 1.535 (95% CI: 1.082-2.177, p=0.016) and 1.668 (95% CI: 1.187-2.344, p=0.003). The rates of grade ≥3 complications related to LCT was mostly low (<10%) and not significantly higher compared to the control arm. ConclusionPooled analyses results of all included studies, selected studies with reliable comparability, and RCT's demonstrated the survival benefit of LCT. These consistent results suggest that LCT was beneficial to the patients with oligometastasis.

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“…In the subgroup analysis of OS, sintilimab plus radiotherapy appeared to be beneficial in male patients, patients under 65 years old, and patients with less than 2 lines of previous systemic therapy. A study also suggested that in patients with oligometastatic NSCLC, single-site radiotherapy plus immunotherapy was more beneficial in patients with 1 to 2 metastases (28). There are still numerous questions about the impact of various radiotherapy dosage and methods on the magnitude of immune prognosis than conventional radiotherapy (29).…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy improves the outcomes of immunotherapy with Sintilimab in non-small-cell lung cancer: A real-world analysis

Chen

Yang

et al. 2022

Front. Immunol.

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Introduction: Radiotherapy may augment systemic antitumor responses to immunotherapy. We did a retrospective study to infer whether radiotherapy improves outcomes to immunotherapy in patients with stage III and IV nonsmall-cell lung cancer (NSCLC).Methods: This retrospective study conducted at Enze Medical Center enrolled 259 patients with histopathology confirmed NSCLC from December 2018 to December 31, 2021. All were treated with Sintilimab, some patients received radiotherapy at an appropriate time point. Radiation type includes conventional radiotherapy and stereotactic body radiotherapy. The progression-free survival (PFS), and overall survival (OS) were the primary endpoint.Results: A retrospective analysis was performed on 259 patients, of whom 140 had been treated with immunotherapy lonely and 119 had been remedied with immunotherapy plus radiotherapy. Baseline variables were well balanced between the two groups, including gender, age, smoking status, TNM staging, number of metastases, ECOG score, pathological type and lines of previous systemic therapy. The median PFS in the immunotherapy alone group was 5.00 months (95%CI 4.38-5.62) versus immunotherapy plus radiotherapy was 9.00 months (5.95-12.05; p<0.001). The median OS in the immunotherapy alone group was 16.00 months (12.59-19.42) versus immunotherapy plus radiotherapy was 30.00 months (20.75-39.25; p=0.027). PFS was finer in the radiotherapy plus immunotherapy group than the immunotherapy group alone in both stage III (P=0.0069) and Stage IV(P=0.006) patients. In the univariate analysis, radiotherapy, male, ECOG=0 and <2 lines of previous systemic therapy were connected with an observably better PFS (P<0.001; P=0.03; P=0.002;P=0.021). In a multivariate analysis, radiotherapy, ECOG=0 and <2 lines of previous systemic therapy were independent prognostic factors with a markedly better Frontiers in Immunology frontiersin.org 01

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Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

Cited by 13 publications

References 33 publications

Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis

Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis

Role of Local Treatment for Oligometastasis: A Comparability Based Meta-Analysis

Radiotherapy improves the outcomes of immunotherapy with Sintilimab in non-small-cell lung cancer: A real-world analysis

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