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Radiation pneumonitis after definitive chemoradiation and durvalumab for non-small cell lung cancer

2020; Elsevier BV; Volume: 150; Linguagem: Inglês

10.1016/j.lungcan.2020.08.022

1872-8332

Khinh Ranh Voong, Jarushka Naidoo,

Effects of Radiation Exposure

Pneumonitis is an uncommon but potentially fatal adverse event of both radiotherapy (RT) [ [1] Whitfield A.G. Lannigan R. Bond W.H. Fatal post-radiation pneumonitis. Lancet. 1954; 267: 117-119 Abstract PubMed Scopus (3) Google Scholar ] and anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC [ [2] Suresh K. Voong K.R. Shankar B. Forde P.M. Ettinger D.S. Marrone K.A. Kelly R.J. Hann C.L. Levy B. Feliciano J.L. Brahmer J.R. Feller-Kopman D. Lerner A.D. Lee H. Yarmus L. D’Alessio F. Hales R.K. Lin C.T. Psoter K.J. Danoff S.K. Naidoo J. Pneumonitis in non-small cell lung Cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors. J. Thorac. Oncol. 2018; 13: 1930-1939 Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar ]. Symptomatic radiation (RT-) pneumonitis following chemoradiation can occur in up to 30% of patients, with 1%–16% of them requiring supplemental oxygen and 2% resulting in death [ 3 O’Rourke N. Roqué I Figuls M. Farré Bernadó N. Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst. Rev. 2010; 6: CD002140 PubMed Google Scholar , 4 Chun S.G. Hu C. Choy H. Komaki R.U. Timmerman R.D. Schild S.E. Bogart J.A. Dobelbower M.C. Bosch W. Galvin J.M. Kavadi V.S. Narayan S. Iyengar P. Robinson C.G. Wynn R.B. Raben A. Augspurger M.E. MacRae R.M. Paulus R. Bradley J.D. Impact of intensity-modulated radiation therapy technique for locally advanced non-small-Cell lung Cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. J. Clin. Oncol. 2017; 35: 56-62 Crossref PubMed Scopus (412) Google Scholar , 5 Palma D.A. Senan S. Tsujino K. Barriger R.B. Rengan R. Moreno M. Bradley J.D. Kim T.H. Ramella S. Marks L.B. De Petris L. Stitt L. Rodrigues G. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int. J. Radiat. Oncol. Biol. Phys. 2013; 85: 444-450 Abstract Full Text Full Text PDF PubMed Scopus (410) Google Scholar ]. The incidence of ICI-related (ICI-) pneumonitis following anti-PD-1/PD-L1 monotherapy or combinations, ranges from 1%–10% [ [6] Topalian S.L. Hodi F.S. Brahmer J.R. Gettinger S.N. Smith D.C. McDermott D.F. Powderly J.D. Carvajal R.D. Sosman J.A. Atkins M.B. Leming P.D. Spigel D.R. Antonia S.J. Horn L. Drake C.G. Pardoll D.M. Chen L. Sharfman W.H. Anders R.A. Taube J.M. McMiller T.L. Xu H. Korman A.J. Jure-Kunkel M. Agrawal S. McDonald D. Kollia G.D. Gupta A. Wigginton J.M. Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 2012; 366: 2443-2454 Crossref PubMed Scopus (8830) Google Scholar , [7] Nishino M. Ramaiya N.H. Awad M.M. Sholl L.M. Maattala J.A. Taibi M. Hatabu H. Ott P.A. Armand P.F. Hodi F.S. PD-1 inhibitor-related pneumonitis in advanced Cancer patients: radiographic patterns and clinical course. Clin. Cancer Res. 2016; 22: 6051-6060 Crossref PubMed Scopus (289) Google Scholar ]. Recently, the addition of 1 year of maintenance anti-PD-L1 therapy after definitive chemoradiation has become a new standard-of-care for patients with medically inoperable stage III NSCLC. This is based on the findings of a phase III trial called PACIFIC, in which maintenance durvalumab significantly reduced cancer progression, and improved overall survival (HR 0.68) [ [8] Antonia S.J. Villegas A. Daniel D. Vicente D. Murakami S. Hui R. Kurata T. Chiappori A. Lee K.H. de Wit M. Cho B.C. Bourhaba M. Quantin X. Tokito T. Mekhail T. Planchard D. Kim Y.C. Karapetis C.S. Hiret S. Ostoros G. Kubota K. Gray J.E. Paz-Ares L. de Castro Carpeño J. Faivre-Finn C. Reck M. Vansteenkiste J. Spigel D.R. Wadsworth C. Melillo G. Taboada M. Dennis P.A. Özgüroğlu M. Investigators P. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N. Engl. J. Med. 2018; 379: 2342-2350 Crossref PubMed Scopus (1432) Google Scholar , [9] Antonia S.J. Villegas A. Daniel D. Vicente D. Murakami S. Hui R. Yokoi T. Chiappori A. Lee K.H. de Wit M. Cho B.C. Bourhaba M. Quantin X. Tokito T. Mekhail T. Planchard D. Kim Y.C. Karapetis C.S. Hiret S. Ostoros G. Kubota K. Gray J.E. Paz-Ares L. de Castro Carpeño J. Wadsworth C. Melillo G. Jiang H. Huang Y. Dennis P.A. Özgüroğlu M. Investigators P. Durvalumab after Chemoradiotherapy in stage III non-small-Cell lung Cancer. N. Engl. J. Med. 2017; 377: 1919-1929 Crossref PubMed Scopus (2218) Google Scholar ]. However, the benefits of this additive therapy is not without risk. While preclinical studies and clinical observations support potential immunologic synergy between RT and ICIs, there is also potential for increased toxicity [ [10] Deng L. Liang H. Burnette B. Beckett M. Darga T. Weichselbaum R.R. Fu Y.X. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J. Clin. Invest. 2014; 124: 687-695 Crossref PubMed Scopus (1225) Google Scholar , [11] Golden E.B. Demaria S. Schiff P.B. Chachoua A. Formenti S.C. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol. Res. 2013; 1: 365-372 Crossref PubMed Scopus (497) Google Scholar ]. For example, in the PACIFIC study, an absolute increase in rates of RT-pneumonitis as well as ICI-pneumonitis was seen in patients treated with durvalumab when compared to chemoradiation alone (RT-pneumonitis - any grade: 20% vs. 16%, grade 3+: 1.5% vs. 0.4%; ICI-Pneumonitis - any grade: 13% vs. 8%, respectively) [ [8] Antonia S.J. Villegas A. Daniel D. Vicente D. Murakami S. Hui R. Kurata T. Chiappori A. Lee K.H. de Wit M. Cho B.C. Bourhaba M. Quantin X. Tokito T. Mekhail T. Planchard D. Kim Y.C. Karapetis C.S. Hiret S. Ostoros G. Kubota K. Gray J.E. Paz-Ares L. de Castro Carpeño J. Faivre-Finn C. Reck M. Vansteenkiste J. Spigel D.R. Wadsworth C. Melillo G. Taboada M. Dennis P.A. Özgüroğlu M. Investigators P. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N. Engl. J. Med. 2018; 379: 2342-2350 Crossref PubMed Scopus (1432) Google Scholar ]. Similarly, a large single institution retrospective series of stage IV NSCLC patients who received ICI and subsequently developed ICI-pneumonitis similarly found numerically increased rates of ICI- pneumonitis in the subset of patients who had previously received definitive-intent thoracic RT [ [12] Voong K.R. Hazell S.Z. Fu W. Hu C. Lin C.T. Ding K. Suresh K. Hayman J. Hales R.K. Alfaifi S. Marrone K.A. Levy B. Hann C.L. Ettinger D.S. Feliciano J.L. Peterson V. Kelly R.J. Brahmer J.R. Forde P.M. Naidoo J. Relationship between prior radiotherapy and checkpoint-inhibitor pneumonitis in patients with advanced non-small-Cell lung Cancer. Clin. Lung Cancer. 2019; 20: e470-e479 Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar ]. Given the morbidity associated with pneumonitis and its increasing relevance in stage III NSCLC, our ability to understand the real-world incidence and to optimally identify those at risk for both RT-pneumonitis and ICI-pneumonitis is crucial. Herein, we will review the findings of a retrospective study focusing on the real-world experience of durvalumab after chemoradiation in an Asian population of patients with stage III NSCLC, compare and contrast these findings with those of the flagship PACIFIC study and other published data, and examine how these data inform future questions on RT-pneumonitis in stage III NSCLC. Real world data of durvalumab consolidation after chemoradiotherapy in stage III non-small-cell lung cancerLung CancerVol. 146PreviewStage III non-small-cell lung cancer (NSCLC) is a heterogeneous set of conditions including potentially resectable disease and unresectable NSCLC. Long-term outcomes are poor with a 5-year overall survival (OS) rate of 15–35 % for stage IIIA and 3–10 % for stage IIIB according to the AJCC 7th edition. Unresectable locally advanced (LA)-NSCLC accounts for about 30–50 % of stage III NSCLC [1]. Randomized phase III trials have shown the superiority of concurrent chemo-radiotherapy (CCRT) compared with sequential chemoradiotherapy in patients with unresectable LA-NSCLC [2,3]. Full-Text PDF