Real-world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non-small cell lung cancer

被引:28
作者
Huang, Yiqing [1 ]
Zhao, Joseph J. [2 ]
Soon, Yu Yang [3 ]
Wong, Alvin [1 ]
Aminkeng, Folefac [4 ]
Ang, Yvonne [1 ]
Asokumaran, Yugarajah [1 ]
Low, Jia Li [1 ]
Lee, Matilda [1 ]
Choo, Joan R. E. [1 ]
Chan, Gloria [1 ]
Kee, Adrian [5 ]
Tay, Sen Hee [6 ]
Goh, Boon Cher [1 ]
Soo, Ross A. [1 ]
机构
[1] Natl Univ Canc Inst Singapore, Dept Haematol Oncol, 1E Kent Ridge Rd,NUHS Tower Block,Level 7, Singapore 119228, Singapore
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore
[3] Natl Univ Canc Inst Singapore, Dept Radiat Oncol, Singapore, Singapore
[4] Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore
[5] Natl Univ Singapore Hosp, Dept Med, Resp Med Div, Singapore, Singapore
[6] Natl Univ Singapore Hosp, Dept Med, Rheumatol Div, Singapore, Singapore
基金
英国医学研究理事会; 新加坡国家研究基金会;
关键词
consolidation; Durvalumab; non-small cell lung cancer; real-world; stage III; TO-LYMPHOCYTE RATIO; EGFR MUTATION; CLINICAL-OUTCOMES; SUBGROUP ANALYSIS; NSCLC; ONCOLOGY; CHEMORADIATION; RADIOTHERAPY; HALLMARKS; PATTERNS;
D O I
10.1111/1759-7714.14667
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Durvalumab consolidation is associated with improved survival following concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, in this study we evaluated the efficacy and safety of durvalumab in the real-world setting. Method Unresectable stage III NSCLC patients were retrospectively studied: one cohort received CCRT, another had CCRT-durvalumab. Primary endpoints were progression-free survival (PFS) and overall survival (OS), secondary endpoints were relapse rate and safety. In CCRT-durvalumab cohort, association between blood markers with survival and pneumonitis risk were analyzed. Results A total of 84 patients were enrolled: 45 received CCRT, and 39 received CCRT-durvalumab. Median PFS was 17.5 months for CCRT-durvalumab and 8.9 months for CCRT-alone (HR 0.47, p = 0.038). Median OS was not-reached for CCRT-durvalumab and 22.3 months for CCRT-alone (HR 0.35, p = 0.024). Both EGFR-positive and wild-type (WT) patients had numerically improved PFS with durvalumab consolidation compared to CCRT-alone, 17.5 versus 10.9 months and 11.8 versus 6.63 months, respectively (interaction p-value = 0.608). Grade 2+ pneumonitis was detected in 25% of patients in the durvalumab cohort. Most pneumonitis occurred at 3.5 weeks after durvalumab initiation. Baseline neutrophil-to-lymphocyte ratio (NLR) >= 3 and >= 5 were associated with shorter PFS with durvalumab. Week 6 platelet-lymphocyte-ratio >= 180 was associated with a lower risk of pneumonitis. Conclusion In this real-world study, durvalumab consolidation post CCRT was associated with a statistically significant improvement in PFS and OS. Effect of durvalumab on PFS was not modified by EGFR status. Active surveillance for pneumonitis is crucial. Baseline NLR may help to predict the benefit of treatment with durvalumab.
引用
收藏
页码:3152 / 3161
页数:10
相关论文
共 41 条
[1]   Effect of durvalumab on local control after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer in comparison with chemoradiotherapy alone [J].
Abe, Takanori ;
Saito, Satoshi ;
Iino, Misaki ;
Aoshika, Tomomi ;
Ryuno, Yasuhiro ;
Ohta, Tomohiro ;
Igari, Mitsunobu ;
Hirai, Ryuta ;
Kumazaki, Yu ;
Miura, Yu ;
Kaira, Kyoichi ;
Kagamu, Hiroshi ;
Noda, Shin-ei ;
Kato, Shingo .
THORACIC CANCER, 2021, 12 (02) :245-250
[2]   Gefitinib With Concurrent Thoracic Radiotherapy in Unresectable Locally Advanced NSCLC With EGFR Mutation; West Japan Oncology Group 6911L [J].
Akamatsu, Hiroaki ;
Murakami, Haruyasu ;
Harada, Hideyuki ;
Shimizu, Junichi ;
Hayashi, Hidetoshi ;
Daga, Haruko ;
Hasegawa, Yoshikazu ;
Kim, Young Hak ;
Kato, Terufumi ;
Tokunaga, Shoji ;
Nishimura, Yasumasa ;
Yamamoto, Nobuyuki ;
Nakagawa, Kazuhiko .
JOURNAL OF THORACIC ONCOLOGY, 2021, 16 (10) :1745-1752
[3]   Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer [J].
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 Carpeno, J. ;
Wadsworth, C. ;
Melillo, G. ;
Jiang, H. ;
Huang, Y. ;
Dennis, P. A. ;
Ozguroglu, M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (20) :1919-1929
[4]   Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy [J].
Aredo, Jacqueline V. ;
Mambetsariev, Isa ;
Hellyer, Jessica A. ;
Amini, Arya ;
Neal, Joel W. ;
Padda, Sukhmani K. ;
McCoach, Caroline E. ;
Riess, Jonathan W. ;
Cabebe, Elwyn C. ;
Naidoo, Jarushka ;
Abuali, Tariq ;
Salgia, Ravi ;
Loo Jr, Billy W. ;
Diehn, Maximilian ;
Han, Summer S. ;
Wakelee, Heather A. .
JOURNAL OF THORACIC ONCOLOGY, 2021, 16 (06) :1030-1041
[5]  
AstraZeneca, 2021, PHAS 2 OP LAB MULT I
[6]  
AstraZeneca, 2021, PHAS 3 RAND PLAC CON
[7]   Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non-Small-Cell Lung Cancer [J].
Auperin, Anne ;
Le Pechoux, Cecile ;
Rolland, Estelle ;
Curran, Walter J. ;
Furuse, Kiyoyuki ;
Fournel, Pierre ;
Belderbos, Jose ;
Clamon, Gerald ;
Ulutin, Hakki Cuneyt ;
Paulus, Rebecca ;
Yamanaka, Takeharu ;
Bozonnat, Marie-Cecile ;
Uitterhoeve, Apollonia ;
Wang, Xiaofei ;
Stewart, Lesley ;
Arriagada, Rodrigo ;
Burdett, Sarah ;
Pignon, Jean-Pierre .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (13) :2181-2190
[8]   Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study [J].
Bradley, Jeffrey D. ;
Paulus, Rebecca ;
Komaki, Ritsuko ;
Masters, Gregory ;
Blumenschein, George ;
Schild, Steven ;
Bogart, Jeffrey ;
Hu, Chen ;
Forster, Kenneth ;
Magliocco, Anthony ;
Kavadi, Vivek ;
Garces, Yolanda I. ;
Narayan, Samir ;
Iyengar, Puneeth ;
Robinson, Cliff ;
Wynn, Raymond B. ;
Koprowski, Christopher ;
Meng, Joanne ;
Beitler, Jonathan ;
Gaur, Rakesh ;
Curran, Walter, Jr. ;
Choy, Hak .
LANCET ONCOLOGY, 2015, 16 (02) :187-199
[9]   Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial [J].
Butts, Charles ;
Socinski, Mark A. ;
Mitchell, Paul L. ;
Thatcher, Nick ;
Havel, Libor ;
Krzakowski, Maciej ;
Nawrocki, Sergiusz ;
Ciuleanu, Tudor-Eliade ;
Bosquee, Lionel ;
Manuel Trigo, Jose ;
Spira, Alexander ;
Tremblay, Lise ;
Nyman, Jan ;
Ramlau, Rodryg ;
Wickart-Johansson, Gun ;
Ellis, Peter ;
Gladkov, Oleg ;
Pereira, Jose Rodrigues ;
Eberhardt, Wilfried Ernst Erich ;
Helwig, Christoph ;
Schroeder, Andreas ;
Shepherd, Frances A. .
LANCET ONCOLOGY, 2014, 15 (01) :59-68
[10]   Oncology Meets Immunology: The Cancer-Immunity Cycle [J].
Chen, Daniel S. ;
Mellman, Ira .
IMMUNITY, 2013, 39 (01) :1-10