Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial
Narek Shaverdian,Aaron Lisberg,Krikor Bornazyan,Darlene Veruttipong,Jonathan W. Goldman,Silvia C. Formenti,Edward B. Garon,Percy Lee +7 more
TLDR
This trial aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonaryoxicity in the intention-to-treat population.Abstract:
Summary Background Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. Methods We assessed patients with advanced NSCLC treated on the phase 1 KEYNOTE-001 trial at a single institution (University of California, Los Angeles, CA, USA). Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 1 or less, had adequate organ function, and no history of pneumonitis. Patients received pembrolizumab at a dose of either 2 mg/kg of bodyweight or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. Disease response and pulmonary toxicity were prospectively assessed by Immune-related Response Criteria and Common Terminology Criteria for Adverse Events version 4.0. The primary objective of the KEYNOTE-001 trial was to assess the safety, side-effect profile, and antitumour activity of pembrolizumab. For our secondary analysis, patients were divided into subgroups to compare patients who previously received radiotherapy with patients who had not. Our primary objective was to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonary toxicity in the intention-to-treat population. The KEYNOTE-001 trial was registered with ClinicalTrials.gov, number NCT01295827. Findings Between May 22, 2012, and July 11, 2014, 98 patients were enrolled and received their first cycle of pembrolizumab. One patient was lost to follow-up. 42 (43%) of 97 patients had previously received any radiotherapy for the treatment of NSCLC before the first cycle of pembrolizumab. 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients received thoracic radiotherapy. Median follow-up for surviving patients was 32·5 months (IQR 29·8–34·1). Progression-free survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (hazard ratio [HR] 0·56 [95% CI 0·34–0·91], p=0·019; median progression-free survival 4·4 months [95% CI 2·1–8·6] vs 2·1 months [1·6–2·3]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (HR 0·50 [0·30–0·84], p=0·0084; median progression-free survival 6·3 months [95% CI 2·1–10·4] vs 2·0 months [1·8–2·1]). Overall survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (HR 0·58 [95% CI 0·36–0·94], p=0·026; median overall survival 10·7 months [95% CI 6·5–18·9] vs 5·3 months [2·7–7·7]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (0·59 [95% CI 0·36–0·96], p=0·034; median overall survival 11·6 months [95% CI 6·5–20·5] vs 5·3 months [3·0–8·5]). 15 (63%) of 24 patients who had previously received thoracic radiotherapy had any recorded pulmonary toxicity versus 29 (40%) of 73 patients with no previous thoracic radiotherapy. Three (13%) patients with previous thoracic radiotherapy had treatment-related pulmonary toxicity compared with one (1%) of those without; frequency of grade 3 or worse treatment-related pulmonary toxicities was similar (one patient in each group). Interpretation Our data suggest that previous treatment with radiotherapy in patients with advanced NSCLC results in longer progression-free survival and overall survival with pembrolizumab treatment than that seen in patients who did not have previous radiotherapy, with an acceptable safety profile. Further clinical trials investigating this combination are needed to determine the optimal treatment strategy for patients with advanced NSCLC. Funding US National Institutes of Health.read more
Citations
More filters
Journal ArticleDOI
Nebenwirkungsprofil einer frühen Immuntherapie nach Radiotherapie
Lukas Seiß,Thomas Brunner +1 more
Journal ArticleDOI
Prise en charge des cancers bronchiques non à petites cellules oligométastatiques: Management of non-small oligometastatic lung cancer: Update 2021
TL;DR: In this paper, Masson et al. introduce the notion of maladie oligometastatique, which is defined as a set of patients who are atteints d'une seule metastase extra-thoracique (stade M1b) and plusieurs metastases extrathoraciques dans un ou plusieur organes.
Journal ArticleDOI
Liquid biopsy for tumor mutational burden predicts the effectiveness of atezolizumab in non-small cell lung cancer treatment
Takehiro Uemura,Toyoaki Hida +1 more
TL;DR: Three ICIs for second-line treatment of NSCLC have been approved and randomized studies have shown superior overall survival (OS) associated with ICIs, compared to second- line docetaxel (1-4).
Journal ArticleDOI
Clinical management of immune-related adverse events following immunotherapy treatment in patients with non-small cell lung cancer.
TL;DR: In this paper, the authors describe the mechanism of action and toxicities associated with immune checkpoint blockade in patients with lung cancer and provide a framework for management of adverse events and adverse events.
Journal ArticleDOI
Efficacy of different therapies for brain metastases of non-small cell lung cancer: a systematic review and meta-analysis
TL;DR: In this paper , the authors conducted a meta-analysis to investigate the potential benefit of different therapeutic regimens for intracranial lesions in non-targeted therapy NSCLC patients.
References
More filters
Journal ArticleDOI
Cancer statistics, 2016
TL;DR: Overall cancer incidence trends are stable in women, but declining by 3.1% per year in men, much of which is because of recent rapid declines in prostate cancer diagnoses, and brain cancer has surpassed leukemia as the leading cause of cancer death among children and adolescents.
Journal ArticleDOI
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Martin Reck,Delvys Rodriguez-Abreu,Andrew G. Robinson,Rina Hui,Tibor Csőszi,Andrea Fülöp,Maya Gottfried,Nir Peled,Ali Tafreshi,Sinead Cuffe,Mary O'Brien,Suman Rao,Katsuyuki Hotta,Melanie A. Leiby,Gregory M. Lubiniecki,Yue Shentu,Reshma A. Rangwala,Julie R. Brahmer +17 more
TL;DR: 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 PD-L1 as mentioned in this paper.
Journal ArticleDOI
Pembrolizumab for the treatment of non-small cell lung cancer
Edward B. Garon,Naiyer A. Rizvi,Rina Hui,Natasha B. Leighl,Ani Sarkis Balmanoukian,Joseph Paul Eder,Amita Patnaik,Charu Aggarwal,Matthew A. Gubens,Leora Horn,Enric Carcereny,Myung-Ju Ahn,Enriqueta Felip,Jong-Seok Lee,Matthew D. Hellmann,Omid Hamid,Jonathan W. Goldman,Jean-Charles Soria,Marisa Dolled-Filhart,Ruth Z. Rutledge,Jin Zhang,Jared Lunceford,Reshma A. Rangwala,Gregory M. Lubiniecki,Charlotte Roach,Kenneth Emancipator,Leena Gandhi +26 more
TL;DR: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer and PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolIZumab.
Journal ArticleDOI
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.
Roy S. Herbst,Paul Baas,Dong Wan Kim,Enriqueta Felip,Jose Luis Perez-Gracia,Ji Youn Han,Julian R. Molina,Joo Hang Kim,Catherine Dubos Arvis,Myung-Ju Ahn,Margarita Majem,Mary J. Fidler,Gilberto de Castro,Marcelo Garrido,Gregory M. Lubiniecki,Yue Shentu,Ellie Im,Marisa Dolled-Filhart,Edward B. Garon +18 more
TL;DR: In this article, the authors evaluated the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.
Journal ArticleDOI
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
Jedd D. Wolchok,Axel Hoos,Steven J. O'Day,Jeffrey S. Weber,Omid Hamid,Céleste Lebbé,Michele Maio,Michael Binder,Oliver Bohnsack,Geoffrey M. Nichol,R. Humphrey,F. Stephen Hodi +11 more
TL;DR: Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria.
Related Papers (5)
Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
Scott J. Antonia,A. Villegas,Davey B. Daniel,David Vicente,Shuji Murakami,Rina Hui,Takashi Yokoi,Alberto Chiappori,Ki Hyeong Lee,Maike de Wit,Byoung Chul Cho,M. Bourhaba,Xavier Quantin,Takaaki Tokito,Tarek Mekhail,David Planchard,Young-Chul Kim,Christos S. Karapetis,Sandrine Hiret,Gyula Ostoros,Kaoru Kubota,Jhanelle E. Gray,Luis Paz-Ares,Javier de Castro Carpeño,Catherine Wadsworth,Giovanni Melillo,Haiyi Jiang,Y. Huang,Phillip A. Dennis,Mustafa Ozguroglu,Pacific Investigators +30 more
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer
Julie R. Brahmer,Karen L. Reckamp,Paul Baas,Lucio Crinò,Wilfried Eberhardt,Elena Poddubskaya,Scott J. Antonia,Adam Pluzanski,Everett E. Vokes,Esther Holgado,David M. Waterhouse,Neal Ready,Justin F. Gainor,Osvaldo Arén Frontera,Libor Havel,Martin Steins,Marina Chiara Garassino,Joachim G.J.V. Aerts,Manuel Domine,Luis Paz-Ares,Martin Reck,Christine Baudelet,Christopher T. Harbison,Brian Lestini,David R. Spigel +24 more
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Christina Twyman-Saint Victor,Andrew J. Rech,Amit Maity,Ramesh Rengan,Ramesh Rengan,Kristen E. Pauken,Erietta Stelekati,Joseph L. Benci,Bihui Xu,Hannah Dada,Pamela M. Odorizzi,Ramin S. Herati,Kathleen D. Mansfield,Dana Patsch,Ravi K. Amaravadi,Lynn M. Schuchter,Hemant Ishwaran,Rosemarie Mick,Daniel A. Pryma,Xiaowei Xu,Michael Feldman,Tara C. Gangadhar,Stephen M. Hahn,E. John Wherry,Robert H. Vonderheide,Andy J. Minn +25 more