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      Radiation and immune checkpoint inhibitors in the treatment of oligometastatic non-small-cell lung cancer: a practical review of rationale, recent data, and research questions

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          Abstract

          The combined use of stereotactic ablative radiotherapy (SABR) and immune checkpoint inhibitors (ICIs) is an emerging treatment paradigm for oligometastatic non-small-cell lung cancer (NSCLC). Recent phase I and II trial data suggest that SABR to multiple metastases in addition to ICI use is safe and effective with promising progression-free survival and overall survival signals. There is great interest in capitalizing on combined immunomodulation from these two modalities for the treatment of oligometastatic NSCLC. Ongoing trials seek to validate the safety, efficacy, and preferred sequencing of SABR and ICI. This narrative review of the role of SABR when combined with ICI in oligometastatic NSCLC discusses the rationale for this bimodality treatment, summarizes recent clinical trial evidence, and proposes key principles of management based on the available evidence.

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          Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

          Martin Reck, Delvys Rodriguez-Abreu, Andrew G Robinson … (2016)
          Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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            Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

            Scott J Antonia, Augusto Villegas, Davey Daniel … (2017)
            Background Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. Methods We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. Results Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. Conclusions Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
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              CTLA-4 and PD-1 Pathways

              Elizabeth I Buchbinder, Anupam Desai (2016)
              Supplemental Digital Content is available in the text.
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                Author and article information

                Contributors
                Sondos Zayed: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Alexander V. Louie: Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Daniel A. Breadner:
                ORCID: https://orcid.org/0000-0001-5379-7621
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                David A. Palma: Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Rohann J. M. Correa: Role: ConceptualizationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Journal
                Journal ID (nlm-ta): Ther Adv Med Oncol
                Journal ID (iso-abbrev): Ther Adv Med Oncol
                Journal ID (publisher-id): TAM
                Journal ID (hwp): sptam
                Title: Therapeutic Advances in Medical Oncology
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 1758-8340
                ISSN (Electronic): 1758-8359
                Publication date (Electronic): 8 July 2023
                Publication date Collection: 2023
                Volume: 15
                Electronic Location Identifier: 17588359231183668
                Affiliations
                [1-17588359231183668]Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada
                [2-17588359231183668]Department of Radiation Oncology, Sunnybrook Hospital Odette Cancer Centre, Toronto, ON, Canada
                [3-17588359231183668]Department of Medical Oncology, London Health Sciences Centre, London, ON, Canada
                [4-17588359231183668]Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada
                [5-17588359231183668]Department of Radiation Oncology, London Health Sciences Centre, 800 Commissioners Rd East, London, ON N6A 5W9, Canada
                Author notes
                Author information
                https://orcid.org/0000-0001-5379-7621
                Article
                Publisher ID: 10.1177_17588359231183668
                DOI: 10.1177/17588359231183668
                PMC ID: 10331344
                PubMed ID: 37435562
                SO-VID: 57ac8eb3-6622-4508-a081-31756d097abc
                Copyright © © The Author(s), 2023
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 15 August 2022
                Date accepted : 31 May 2023
                Categories
                Subject: Controversies in Immunotherapy for Patients with Lung Cancer: Pragmatic Solutions
                Subject: Review
                Custom metadata
                cover-date January-December 2023
                typesetter ts1

                Keywords: immune checkpoint inhibitors,immunotherapy,non-small-cell lung cancer,oligometastasis,stereotactic ablative radiotherapy
                Data availability:
                Keywords: immune checkpoint inhibitors, immunotherapy, non-small-cell lung cancer, oligometastasis, stereotactic ablative radiotherapy

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