MA04.01 Cemiplimab, a Human Monoclonal Anti-PD-1, Alone or in Combination with Radiotherapy: Phase 1 NSCLC Expansion Cohorts

Moreno, Víctor; Gil-Martín, Marta; Johnson, Melissa L.; Aljumaily, Raid; Lopez-Criado, M.P.; Northfelt, DW; Crittenden, Marka R.; Jabbour, Salma K.; Rosen, L.; Calvo, Emiliano; Papadopoulos, Kyriakos P.; Garrido, Pilar; Morón, A. Hervás; Rietschel, Petra; Mohan, Kosalai Kal; Li, J.; Stankevich, Elizabeth; Ma, Feng; Lowy, Israel; Fury, Matthew G.

doi:10.1016/j.jtho.2018.08.340

Cited by 16 publications

(13 citation statements)

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“…This study was not randomized, but rather was comprised of a comparison of two separate phase I expansion cohorts in which patients either received cemiplimab alone (n=20) or cemiplimab in combination with SBRT (27 Gy in 3 fractions; n=33). As was the case in the aforementioned studies, the addition of SBRT to ICB did not appear to result in a significantly higher rate of toxicity, though it is important to note that one patient in the experimental arm experienced grade 5 pneumonitis, which was attributed to treatment; furthermore, the addition of SBRT to ICB once again failed to improve ORR (125).…”

Section: Comparative Studies Evaluating the Addition Of Sbrt To Icbmentioning

confidence: 71%

“…Many of the studies examining the combination of the ICB with SBRT have done so under the premise that radiation can act as an adjuvant that stimulates the activity of ICB, with the goal of achieving abscopal responses at unirradiated sites. However, recent attempts to induce this type of abscopal response with non-ablative doses of radiation in combination with ICB have failed to produce robust therapeutic responses (121,125,143). While, SBRT certainly has the potential for synergy with immunotherapy resulting in effects outside of the irradiated field, the local benefits of ablative radiation suggest that it plays an important role beyond acting as an adjuvant.…”

Section: Innovations In Metastasis-directed Sbrtmentioning

confidence: 99%

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The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review

Turchan¹,

Chmura²

2021

Ann Palliat Med

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Metastatic disease is a significant cause of morbidity and mortality among patients with cancer.Patients with oligometastatic cancer represent a subset of the metastatic population with a limited amount of disease that has metastasized distantly and progresses at a slow pace and thus has the potential to be cured with metastasis-directed local therapy. Recent studies examining the role of metastasis-directed therapy in patients with oligometastatic disease have primarily focused upon treatment with ablative doses of radiation, commonly referred to as stereotactic body radiation therapy (SBRT). While the use of SBRT to treat oligometastases has increased considerably in recent years, the benefit of this approach has yet to be confirmed in phase III randomized controlled trials; moreover, distant failure remains a significant problem in patients with oligometastatic disease treated with SBRT. Given the propensity for distant failure in patients with oligometastatic disease treated with SBRT, there is growing interest in the utility of combining SBRT with systemic agents such as immunotherapy. Immunotherapy, and specifically immune checkpoint blockade (ICB), represents a rapidly evolving systemic therapy option with a growing number of indications among patients with metastatic disease; however, despite its promise, only a minority of patients respond to ICB and among those who do, the majority eventually progress. SBRT and ICB are both dependent upon, and have the ability to shift, the balance between antitumor immune surveillance and immunosuppressive states in the tumor and tumor microenvironment. As a result, it has been speculated that SBRT and ICB have the potential to act synergistically when used in combination. SBRT has been demonstrated to be safe in combination with ICB in studies with short-term follow-up and although additional research is needed, preliminary prospective data support the potential efficacy of this approach. In addition to confirming the safety and efficacy of SBRT in combination with immunotherapy, further studies are needed to determine how to maximize the therapeutic ratio of this treatment paradigm for the full potential of immunotherapy in the oligometastatic population to be realized.

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Section: Comparative Studies Evaluating the Addition Of Sbrt To Icbmentioning

confidence: 71%

Section: Innovations In Metastasis-directed Sbrtmentioning

confidence: 99%

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review

Turchan¹,

Chmura²

2021

Ann Palliat Med

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“…The benefit of adding metastasis-directed radiotherapy to immunotherapy has been the subject of a number of comparative phase I/II trials, the designs and results of which are summarized in Table 2. These studies represent a variety of histologies, including NSCLC [36][37][38][39], melanoma [38], HNSCC [40], and adenoid cystic carcinoma (ACC) [41]. With the exception of the report by Curti et al in which patients received interleukin-2 (IL-2) three days after treatment with either 20 Gy or 40 Gy given in 20 Gy fractions [38], patients in these studies were treated with an anti-PD-1/PD-L1 agent [36][37][38][39][40][41].…”

Section: Combined Radio-immunotherapy In Patients With Metastatic Diseasementioning

confidence: 99%

Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the Future May Hold

Turchan

Pitroda

Weichselbaum

2021

IJMS

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Radiotherapy and immunotherapy are most effective as cancer therapies in the setting of low-volume disease. Although initial studies of radio-immunotherapy in patients with metastatic cancer have not confirmed the efficacy of this approach, the role of radio-immunotherapy in patients with limited metastatic burden is unclear. We propose that further investigation of radio-immunotherapy in metastatic patients should focus upon patients with oligometastatic disease.

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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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MA04.01 Cemiplimab, a Human Monoclonal Anti-PD-1, Alone or in Combination with Radiotherapy: Phase 1 NSCLC Expansion Cohorts

Cited by 16 publications

References 0 publications

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review

Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the Future May Hold

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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