Combination of SABR With Anti-PD-1 in Oligoprogressive Non-Small Cell Lung Cancer and Melanoma: Results of a Prospective Multicenter Observational Study.

PURPOSE: The percentage of patients with metastatic non-small cell lung cancer (NSCLC) and melanoma who benefit from anti-programmed cell death protein 1 (anti-PD-1) is low owing to resistance mechanisms. SABR has a role in oligoprogressive disease and can improve responses to anti-PD-1. This multicenter prospective observational study aimed to determine whether concomitant anti-PD-1 and SABR to oligoprogressive sites enhance tumor response in metastatic NSCLC and melanoma. METHODS AND MATERIALS: Patients with metastatic NSCLC or melanoma in progression to anti-PD-1 but continuing the same line owing to clinical benefit were referred for palliative SABR. All patients received concomitant pembrolizumab or nivolumab and SABR to 1 to 5 lesions, maintaining anti-PD-1 until further progression, unacceptable toxicity, or medical/patient decision. Objective response rate-complete responses and partial responses-was evaluated during all follow-up according to Response Evaluation Criteria in Solid Tumors 1.1. The abscopal response was evaluated 8 weeks after SABR as a ≥30% reduction in 1 to 2 predefined nonirradiated lesions. RESULTS: Of the 61 patients enrolled, 50 could be analyzed. With a median follow-up of 32.8 months, objective response rate was 42% (30% complete responses and 12% partial responses). Median progression-free survival was 14.2 months (95% confidence interval, 6.9-29 months). Median overall survival since SABR was 37.4 months (95% confidence interval, 22.9 months-not reached). Abscopal response was 65%, evaluated in 40 patients who fulfilled the criteria. CONCLUSIONS: Combined anti-PD-1 and SABR in oligoprogressive metastatic NSCLC or melanoma can achieve high rates of response and extend the clinical benefit of immunotherapy by delaying further progression and a new systemic therapy. This approach should be assessed in larger randomized trials.

Stereotactic ablative radiotherapy for acquired resistance to EGFR therapy in metastatic non-small cell lung cancer.

The advent of targeted therapy has transformed the treatment paradigm and survival of patients with metastatic non-small cell lung cancer (NSCLC) with driver mutations. The development of acquired resistances during treatment with tyrosine kinase inhibitors (TKIs) impedes a prolonged survival in many patients. This fact is leading to the use of locally ablative therapies such as stereotactic ablative radiotherapy (SABR) to counter these resistances. SABR is a non-invasive treatment that can be delivered in multiple locations and has already proven effective in oligometastatic disease. Clinical evidence suggests that the combination of SABR with TKIs prolongs progression-free survival (PFS) in metastatic NSCLC patients with mutations in epidermal growth factor receptor (EGFR), with international guidelines recommending their use in unfavorable scenarios such as oligoprogressive disease. In this publication, we have reviewed the available evidence on EGFR-TKIs resistance mechanisms and the combination of SABR with TKI in metastatic NSCLC with EGFR mutations. We also describe the utility and clinical recommendations of this combination in oligometastatic and oligoprogressive disease.

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

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.

Stereotactic ablative radiotherapy for oligometastatic breast cancer in elderly patients.

Breast cancer (BC) is the principal cause of cancer-related death in women. Metastatic patients are usually treated with a systemic therapy, but clinical results are limited. Oligometastatic subjects can benefit from high-precision radiotherapy techniques to potentially achieve a complete response. Currently, there is limited evidence of stereotactic ablative radiotherapy (SABR) treatments in elderly oligometastatic cancer patients. A review of the medical literature was performed in PubMed database to assess the current role of SABR in the treatment of breast oligometastases in elderly patients. SABR represents a feasible and safe therapeutic approach in oligometastatic elderly BC patients. Further studies are required to establish the optimum patient selection and treatment scheme.

Stereotactic Ablative Radiotherapy Combined with Immune Checkpoint Inhibitors Reboots the Immune Response Assisted by Immunotherapy in Metastatic Lung Cancer: A Systematic Review.

Background: Immune checkpoint inhibitors (ICI) have represented a revolution in the treatment of non-small-cell lung cancer (NSCLC). To improve these results, combined approaches are being tested. The addition of stereotactic ablative radiotherapy (SABR) to ICI seems promising. A systematic review was performed in order to assess the safety and efficacy of SABR-ICI combination. Material and Methods: MEDLINE databases from 2009 to March 3, 2019 were reviewed to obtain English language studies reporting clinical outcomes of the combination of ICI-SABR in NSCLC. 18 out of the 429 initial results fulfilled the inclusion criteria and were selected for review. Results: Eighteen articles, including six prospective studies, describing 1736 patients treated with an ICI-SABR combination fulfilled the selection criteria. The reported mean rates for local control and distant/abscopal response rates were 71% and 41%, respectively. Eleven studies reported progression-free survival and overall survival, with a mean of 4.6 and 12.4 months, respectively. Toxicity rates were consistent with the ones attributable to ICI treatment alone. Conclusions: The ICI-SABR combination has a good safety profile and achieves high rates of local control and greater chances of obtaining abscopal responses than SABR alone, with a relevant impact on PFS. More studies are needed to improve patient selection for an optimal benefit from this approach.