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Combining immunotherapy with radiation therapy in thoracic oncology.

ABSTRACT: Thoracic malignancies comprise some of the most common and deadly cancers. Immunotherapies have been proven to improve survival outcomes for patients with advanced non-small cell lung cancer (NSCLC) and show great potential for patients with other thoracic malignancies. Radiation therapy (RT), an established and effective treatment for thoracic cancers, has acted synergistically with immunotherapies in preclinical studies. Ongoing clinical trials are exploring the clinical benefits of combining RT with immunotherapies and the optimal manner in which to deliver these complementary treatments.

SUBMITTER: Badiyan SN

PROVIDER: S-EPMC6123189 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Combining immunotherapy with radiation therapy in thoracic oncology.

Badiyan Shahed N SN Roach Michael C MC Chuong Michael D MD Rice Stephanie R SR Onyeuku Nasarachi E NE Remick Jill J Chilukuri Srinivas S Glass Erica E Mohindra Pranshu P Simone Charles B CB

Journal of thoracic disease 20180801 Suppl 21

Thoracic malignancies comprise some of the most common and deadly cancers. Immunotherapies have been proven to improve survival outcomes for patients with advanced non-small cell lung cancer (NSCLC) and show great potential for patients with other thoracic malignancies. Radiation therapy (RT), an established and effective treatment for thoracic cancers, has acted synergistically with immunotherapies in preclinical studies. Ongoing clinical trials are exploring the clinical benefits of combining ...[more]

PMID: 30206494

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Project description:Purpose:The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors. Methods and Materials:Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n?=?79). Receiving both treatments within 1 month was considered concurrent (n?=?35; 44%), and any treatment up to 6 months apart was considered sequential (n?=?44; 56%). The primary endpoint of this study was the rate of Grade ?2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables. Results:A total of 79 patients were identified, with lung cancer (n?=?45) and melanoma (n?=?15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ?2 AEs included pneumonitis (n?=?5; 6%), esophagitis (n?=?6; 8%), and dermatitis (n?=?8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ?2 esophagitis (P?=?.04). Conclusions:Overall, Grade ?2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.

Project description:Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte-associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses.In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ?1 nonirradiated metastasis measuring ?1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment.Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response.This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.

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Combining immunotherapy with radiation therapy in thoracic oncology.

Publications

Combining immunotherapy with radiation therapy in thoracic oncology.

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