Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

Lesueur, Paul; Escande, Alexandre; Thariat, Juliette; Vauléon, E.; Monnet, I.; Cortot, A.; Lerouge, D.; Danhier, S.; Dô, Pascal; Dubos-Arvis, Catherine; Chouaïd, C.; Gervais, Radj

doi:10.1002/cam4.1825

Cited by 41 publications

(40 citation statements)

References 37 publications

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“…Although radiotherapy is likely to prime the immune response [86], most data on combining palliative radiation therapy (intra-and extra-cranial irradiation) with anti-PD-1 [87][88][89][90][91][92] or anti-CTLA-4 inhibitors [87,88,93,94] have not revealed excessive radiation toxicity (compared to those receiving radiotherapy without immunotherapy) or excessive irAEs (compared to those receiving immunotherapy alone). In the NSCLC setting, the safety data were shown to be similar, and combining extrathoracic radiation therapy and ICIs was demonstrated to be safe [95][96][97][98]. In LESUEUR et al [96], ICI-pneumonitis of grade 1-2 occurred in three (4.6%) cases and grade 3-4 in three to four (1.5%) cases among 104 NSCLC patients administered extra-TRT in the 6 months prior, during or in the 3 months following nivolumab treatment.…”

Section: Radiation Pneumonitis or Ici-p In Cancer Patients Receiving mentioning

confidence: 99%

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

et al. 2019

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Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.

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Section: Radiation Pneumonitis or Ici-p In Cancer Patients Receiving mentioning

confidence: 99%

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

et al. 2019

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“…A retrospective analysis of NSCLC metastasized to the brain revealed no significant differences in survival among patients treated with radiation with or without checkpoint inhibitors [179]. A single center retrospective analysis of NSCLC patients showed acceptable adverse reactions in combination therapy of radiotherapy and nivolumab [180]. No relevance of timing of nivolumab on patient outcome was reported in this study.…”

Section: Anti-pd-1 Compared To Anti-ctla-4 Brain Metastasismentioning

confidence: 52%

Radiotherapy as a Backbone for Novel Concepts in Cancer Immunotherapy

Kabiljo

Harpain

Carotta

et al. 2019

Cancers

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Radiation-induced immunogenic cell death has been described to contribute to the efficacy of external beam radiotherapy in local treatment of solid tumors. It is well established that radiation therapy can induce immunogenic cell death in cancer cells under certain conditions. Initial clinical studies combining radiotherapy with immunotherapies suggest a synergistic potential of this approach. Improving our understanding of how radiation reconditions the tumor immune microenvironment should pave the way for designing rational and robust combinations with immunotherapeutic drugs that enhance both local and systemic anti-cancer immune effects. In this review, we summarize irradiation-induced types of immunogenic cell death and their effects on the tumor microenvironment. We discuss preclinical insights on mechanisms and benefits of combining radiotherapy with immunotherapy, focusing on immune checkpoint inhibitors. In addition, we elaborate how these observations were translated into clinical studies and which parameters may be optimized to achieve best results in future clinical trials.

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“…Funded by Chongqing Scienti c Research Institutes performance incentive guide special youth project(cstc2019jxjl0051). HR for PFS James W Welsh, 2019 [43] Angel Qin 2019 [44] Paul Lesueur 2018 [45] Francesco Fiorica 2018 [46] Corey C. Foster 2019 [47] V. Moreno 2017 [48][49][50] Willemijn S. M. E. Theelen 2019 [51] James Welsh 2017 [52] Abraham Flowchart of the study selection procedure Figure 2 Forest plot of the combined ORR, DCR, PFSR6m, or OSR1y of ICIs combined with radiotherapy as treatment for advanced lung cancer. Among the ten studies, seven studies assessed the ORR of ICIs combined with radiotherapy(a).…”

Section: Fundingmentioning

confidence: 99%

The efficacy and safety of immune checkpoints inhibitors plus radiotherapy as a combination therapy for advanced non-small cell lung carcinoma: a meta-analysis

Yang¹,

Li²,

Wang³

et al. 2020

Preprint

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BackgroundImmune checkpoint inhibitors have showed good efficacy in advanced non-small-cell lung cancer(NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of immune checkpoint inhibitors combined with radiotherapy for patients with advanced NSCLC.MethodsWe used many proper keywords to perform a systematic search in databases and performed a meta-analysis of trials that conducted immune checkpoint inhibitors plus radiotherapy as a treatment for advanced non-small-cell lung cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.ResultsTen trials were finally included in this meta-analysis. The combined ORR and DCR was 34% (19%-49%) and 72% (65%-79%). The combined six-month progression-free survival rates (PFSR6m) and one-year overall survival rate(OSR1y) were 50.0% (29.4%-72.8%) and 59.0% (48%-69%). Immune checkpoint inhibitors plus radiotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.64; 95% CI 0.46–0.90; P = 0.01), OS (HR, 0.62; 95% CI 0.46–0.85; P = 0.003). In subgroup analyses, the combined ORR was 31.5% (16.4%-46.6%), combined DCR was 72.1% (63.3%-80.9%), combined PFS6m was 50.0% (20.6%-79.5%) and combined OSR1y was 59.7% (48.1%-71.2%) for anti-PD-1/PD-L1 antibody plus radiotherapy. The combined ORR was 19.5% (9.1%-29.8%) for anti-CTLA4 antibody plus radiotherapy. The combined PFS6m and OSR1y were 58.9% (26.2%-91.7%) and 59.7% (29.7%-89.8%) respectively for the concurrent therapy group. And the combined PFS6m and OS1y were 55.2% (41.6%-68.8%) and 55.7% (42.1%-69.3%) for sequential therapy. For the low-dose radiotherapy group. The combined PFS6m and OS1y were 45.9% (27.0%-64.8%) and 51.6% (37.5%-65.6%). The combined PFS6m and OS1y were 71.1% (37.9%-104.4%) and 67.4% (29.2%-105.6%) separately for high-dose radiotherapy group. When using as first-line therapy. The combined ORR was 53.8% (23.6%-84.1%) and combined ORR was 76.5% (65.0%-88.1%). While as subsequent therapy, the combined ORR and DCR were 25.9% (14.7%-37.2%) and 69.9% (60.9%-78.9%). The combined PFS6m and OS1y were 51.1% (40.3%-61.9%) and 51.8% (40.9%-62.7%).ConclusionsImmune checkpoint inhibitors plus radiotherapy might be an effective and tolerable option as a treatment for advanced NSCLC.

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Safety of combined PD‐1 pathway inhibition and radiation therapy for non‐small‐cell lung cancer: A multicentric retrospective study from the GFPC

Cited by 41 publications

References 37 publications

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

Radiotherapy as a Backbone for Novel Concepts in Cancer Immunotherapy

The efficacy and safety of immune checkpoints inhibitors plus radiotherapy as a combination therapy for advanced non-small cell lung carcinoma: a meta-analysis

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