Prior or concurrent radiotherapy and nivolumab immunotherapy in non–small cell lung cancer

Ratnayake, Gishan; Shanker, Manish; Roberts, Kate; Mason, Robert M.; Hughes, Brett; Lwin, Zarnie; Jain, Vikram; O’Byrne, Kenneth J.; Lehman, Margot

doi:10.1111/ajco.13242

Cited by 13 publications

(11 citation statements)

References 41 publications

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“…Approximately 2027 patients were enrolled in the 20 studies included in this research. With regard to the study design, nine studies were non-randomized controlled trials (NRCT), [6][7][8][23][24][25][26][27][28] nine were single-arm studies, [29][30][31][32][33][34][35][36][37] and two were RCTs. 5,9 All studies included at least one arm treated with combination therapy using PD-1/PD-L1 inhibitors and RT.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…6 Two retrospective studies have shown that combination treatment with RT and nivolumab (a PD-1 inhibitor) in patients with advanced NSCLC may improve OS and PFS without an increase in acute toxicity rates. 7,8 However, a few studies have reported contrasting results. For example, the PEMBRO-RT trial showed that stereotactic body radiotherapy (SBRT) preceding pembrolizumab treatment for metastatic lesions did not improve long-term survival compared with pembrolizumab alone in patients with metastatic NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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Safety and Efficacy of PD‐1/PD‐L1 inhibitors combined with radiotherapy in patients with non‐small‐cell lung cancer: a systematic review and meta‐analysis

et al. 2021

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Background A combination of programmed cell death protein‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non‐small‐cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta‐analysis to summarize the related research. Methods We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta‐analysis. Results The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT was associated with prolonged overall survival (OS) (1‐year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35–2.33, p = 0.000; 2‐year OS: OR 1.77, 95% CI 1.35–2.33, p = 0.000) and progression‐free survival (PFS) (0.5‐year PFS: OR 1.83, 95% CI 1.13–2.98, p = 0.014; 1‐year PFS: OR 2.09, 95% CI 1.29–3.38, p = 0.003; 2‐year PFS: OR 2.47, 95% CI 1.13–5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06–7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21–2.68, p = 0.004). This meta‐analysis showed that compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1–2 immune‐related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD‐1/PD‐L1 inhibitors followed RT outperformed in which concurrent PD‐1/PD‐L1 inhibitor and RT followed PD‐1/PD‐L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD‐1/PD‐L1 inhibitors may be more effective than a combination of conventional RT with PD‐1/PD‐L1 inhibitors in patients with advanced NSCLC. Conclusion Combination therapy using PD‐1/PD‐L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.

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Section: Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of PD‐1/PD‐L1 inhibitors combined with radiotherapy in patients with non‐small‐cell lung cancer: a systematic review and meta‐analysis

et al. 2021

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“…These interesting results led to the analysis of further retrospective data in order to find if these benefits could be replicated. In this regard, both Desideri and Ratnayake found similar results in NSCLC patients, with a trend towards a doubling in PFS and OS in those who had received RT and ICI [50,51]. Despite this encouraging data, several new questions arose with respect to timing, dose escalation and other treatment variables.…”

Section: How Did the Preclinical Evidence For The Combination Of Ici And Rt Translate Into The Clinical Setting?mentioning

confidence: 82%

Immunoradiotherapy as an Effective Therapeutic Strategy in Lung Cancer: From Palliative Care to Curative Intent

Chicas-Sett

Zafra-Martín

Morales-Orue³

et al. 2020

Cancers

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Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), the treatment of metastatic and locally advanced non-small cell lung cancer (NSCLC) has experienced a revolution that has resulted in a significant improvement in overall survival with an enhanced toxicity profile. Despite this paradigm shift, most patients present some kind of resistance to ICI. In this setting, current research is shifting towards the integration of multiple therapies, with RT and ICI being one of the most promising based on the potential immunostimulatory synergy of this combination. This review gives an overview of the evolution and current state of the combination of RT and ICI and provides evidence-based data that can improve patient selection. The combination in lung cancer is a safe therapeutic approach that improves local control and progression-free survival, and it has the potential to unleash abscopal responses. Additionally, this treatment strategy seems to be able to re-sensitize select patients that have reached a state of resistance to ICI, further enabling the continuation of systemic therapy.

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“…In Figure 1 , we can see that sintilimab plus radiotherapy was associated with longer 1-year OS,18-month OS and 2-year OS. A research acted by Theelen W et al ( 15 ), PFS in immunotherapy plus radiotherapy group was notably improved than immunotherapy alone group (p=0.045), and OS was remarkably increased in immunotherapy and radiotherapy group compared with immunotherapy alone group (p=0.0004).A study performed by Gishan et al ( 21 ), there was a significant enhancement in PFS with radiotherapy prior to or concomitant with nivolumab remedy for metastatic NSCLC than nivolumab alone, at the same time, there was no evidence of increased adverse reactions. Additionally, numerous studies show that combining immunotherapy with radiotherapy increases the effectiveness of treatment for NSCLC, with no increase in either radiation or immunological side effects ( 16 , 22 , 23 ).…”

Section: Discussionmentioning

confidence: 97%

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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Prior or concurrent radiotherapy and nivolumab immunotherapy in non–small cell lung cancer

Cited by 13 publications

References 41 publications

Safety and Efficacy of PD‐1/PD‐L1 inhibitors combined with radiotherapy in patients with non‐small‐cell lung cancer: a systematic review and meta‐analysis

Safety and Efficacy of PD‐1/PD‐L1 inhibitors combined with radiotherapy in patients with non‐small‐cell lung cancer: a systematic review and meta‐analysis

Immunoradiotherapy as an Effective Therapeutic Strategy in Lung Cancer: From Palliative Care to Curative Intent

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

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