Top

BMC Pulmonary Medicine

Published in:

Open Access 01-12-2024 | Bevacizumab | Research

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion

Authors: Hao Zeng, Yuanyuan Zhang, Sihan Tan, Qin Huang, Xin Pu, Panwen Tian, Yalun Li

Published in: BMC Pulmonary Medicine | Issue 1/2024

Abstract

Background

Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown.

Methods

Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected.

Results

A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00).

Conclusions

Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Available only for authorised users

Jacobs B, Sheikh G, Youness HA, Keddissi JI, Abdo T. Diagnosis and management of malignant pleural effusion: a decade in review. Diagnostics (Basel Switzerland). 2022;12(4). https://doi.org/10.3390/diagnostics12041016

Taghizadeh N, Fortin M, Tremblay A. US hospitalizations for malignant pleural effusions: data from the 2012 national inpatient sample. Chest. 2017;151(4):845–54. https://doi.org/10.1016/j.chest.2016.11.010.

Tian P, Qiu R, Wang M, Xu S, Cao L, Yang P, Li W. Prevalence, causes, and health care burden of pleural effusions among hospitalized adults in China. JAMA Netw open. 2021;4(8):e2120306. https://doi.org/10.1001/jamanetworkopen.2021.20306 CrossRefPubMedPubMedCentral

Bashour SI, Mankidy BJ, Lazarus DR. Update on the diagnosis and management of malignant pleural effusions. Respir Med. 2022;196:106802https://doi.org/10.1016/j.rmed.2022.106802CrossRef

Zhao Y, Yu L, Wang L, Wu Y, Chen H, Wang Q, Wu Y. Current status of and progress in the treatment of malignant pleural effusion of lung cancer. Front Oncol. 2022;12:961440. https://doi.org/10.3389/fonc.2022.961440CrossRefPubMed

Schwalk AJ, Ost DE, Saltijeral SN, De La Garza H, Casal RF, Jimenez CA, Eapen GA, Lewis J, Rinsurongkawong W, Rinsurongkawong V, et al. Risk factors for and time to recurrence of symptomatic malignant pleural effusion in patients with metastatic non-small cell lung cancer with EGFR or ALK mutations. Chest. 2021;159(3):1256–64. https://doi.org/10.1016/j.chest.2020.10.081CrossRefPubMed

Bibby AC, Dorn P, Psallidas I, Porcel JM, Janssen J, Froudarakis M, Subotic D, Astoul P, Licht P, Schmid R, et al. ERS/EACTS statement on the management of malignant pleural effusions. Eur Respir J. 2018;52(1). https://doi.org/10.1183/13993003.00349-2018

Roberts ME, Rahman NM, Maskell NA, Bibby AC, Blyth KG, Corcoran JP, Edey A, Evison M, de Fonseka D, Hallifax R, et al. British thoracic society guideline for pleural disease. Thorax. 2023. https://doi.org/10.1136/thorax-2023-220304CrossRefPubMed

Feller-Kopman DJ, Reddy CB, DeCamp MM, Diekemper RL, Gould MK, Henry T, Iyer NP, Lee YCG, Lewis SZ, Maskell NA, et al. Management of malignant pleural effusions. An official ATS/STS/STR clinical practice Guideline. Am J Respir Crit Care Med. 2018;198(7):839–49. https://doi.org/10.1164/rccm.201807-1415ST CrossRefPubMed

10.

Du N, Li X, Li F, Zhao H, Fan Z, Ma J, Fu Y, Kang H. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer–mediated malignant pleural effusion. Oncol Rep. 2013;29(6):2332–40. https://doi.org/10.3892/or.2013.2349CrossRefPubMed

11.

Sack U, Hoffmann M, Zhao XJ, Chan KS, Hui DS, Gosse H, Engelmann L, Schauer J, Emmrich F, Hoheisel G. Vascular endothelial growth factor in pleural effusions of different origin. Eur Respir J. 2005;25(4):600–4. https://doi.org/10.1183/09031936.05.00037004CrossRefPubMed

12.

Nie K, Zhang Z, You Y, Zhuang X, Zhang C, Ji Y. A randomized clinical study to compare intrapleural infusion with intravenous infusion of bevacizumab in the management of malignant pleural effusion in patients with non-small-cell lung cancer. Thorac cancer. 2020;11(1):8–14. https://doi.org/10.1111/1759-7714.13238 CrossRefPubMed

13.

Di W, Yue C, Ziran Z, Jie Z, Jun N, Ling D, Weiheng H, Xiaoling C, Xiangjuan M, Guangming T, et al. A phase II study of bevacizumab in non-squamous, non-small-cell lung cancer patients with malignant pleural effusion. Future Oncol. 2022;18(6):669–77. https://doi.org/10.2217/fon-2021-1035CrossRefPubMed

14.

Zhou Z, Li H, Hu D, Xie L. Clinical efficacy of bevacizumab combined with cisplatin in the treatment of malignant pleural effusion and ascites caused by lung cancer: a randomized trial. Annals of Palliative Medicine. 2021;10(10):10575–83. https://doi.org/10.21037/apm-21-2623CrossRefPubMed

15.

Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, et al. Erlotinib plus Bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019;20(5):625–35. https://doi.org/10.1016/s1470-2045(19)30035-xCrossRefPubMed

16.

Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, et al. Bevacizumab plus Erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): a multicenter phase 3 study. Cancer Cell. 2021;39(9):1279–91. https://doi.org/10.1016/j.ccell.2021.07.005CrossRefPubMed

17.

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–60. https://doi.org/10.1097/jto.0000000000000630CrossRefPubMed

18.

Chansky K, Detterbeck FC, Nicholson AG, Rusch VW, Vallières E, Groome P, Kennedy C, Krasnik M, Peake M, Shemanski L, et al. The IASLC lung cancer staging project: external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2017;12(7):1109–21. https://doi.org/10.1016/j.jtho.2017.04.011CrossRefPubMed

19.

Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, Bruno DS, Chang JY, Chirieac LR, D’Amico TA, et al. NCCN guidelines insights: non-small cell lung cancer, version 2.2021. J Natl Compr Canc Netw. 2021;19(3):254–66. https://doi.org/10.6004/jnccn.2021.0013CrossRefPubMed

20.

Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, et al. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv192–iv237. https://doi.org/10.1093/annonc/mdy275CrossRefPubMed

21.

Chaddha U, Agrawal A, Bhavani SV, Sivertsen K, Donington DJ, Ferguson MK, Murgu S. Thoracic ultrasound as a predictor of pleurodesis success at the time of indwelling pleural catheter removal. Respirology. 2021;26(3):249–54. https://doi.org/10.1111/resp.13937CrossRefPubMed

22.

Suzuki K, Servais EL, Rizk NP, Solomon SB, Sima CS, Park BJ, Kachala SS, Zlobinsky M, Rusch VW, Adusumilli PS. Palliation and pleurodesis in malignant pleural effusion: the role for tunneled pleural catheters. J Thorac Oncol. 2011;6(4):762–7. https://doi.org/10.1097/JTO.0b013e31820d614fCrossRefPubMed

23.

Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, Shankar L, Bogaerts J, Chen A, Dancey J, et al. RECIST 1.1-update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7. https://doi.org/10.1016/j.ejca.2016.03.081CrossRefPubMedPubMedCentral

24.

Soo RA, Han JY, Dafni U, Cho BC, Yeo CM, Nadal E, Carcereny E, de Castro J, Sala MA, Bernabé R, et al. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European thoracic oncology platform (ETOP 10–16) BOOSTER trial. Ann Oncol. 2022;33(2):181–92. https://doi.org/10.1016/j.annonc.2021.11.010CrossRefPubMed

25.

Shi Y, Wu L, Yu X, Xing P, Wang Y, Zhou J, Wang A, Shi J, Hu Y, Wang Z et al. Sintilimab versus Docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer: an open-label, randomized controlled phase 3 trial (ORIENT-3). Cancer communications (London, England). 2022; 42(12):1314–30. https://doi.org/10.1002/cac2.12385

26.

Song X, Chen D, Guo J, Kong L, Wang H, Wang Z. Better efficacy of intrapleural infusion of bevacizumab with pemetrexed for malignant pleural effusion mediated from nonsquamous non-small cell lung cancer. Onco Targets Ther. 2018;11:8421–6. https://doi.org/10.2147/ott.S184030CrossRefPubMedPubMedCentral

27.

Xiang Z, Deng X, He W, Yang Q, Ni L, Dehghan Shasaltaneh M, Maghsoudloo M, Yang G, Wu J, Imani S, et al. Treatment of malignant pleural effusion in non-small cell lung cancer with VEGF-directed therapy. Ann Med. 2022;54(1):1357–71. https://doi.org/10.1080/07853890.2022.2071977CrossRefPubMedPubMedCentral

28.

Holling N, Patole S, Medford ARL, Maskell NA, Bibby AC. Is systemic anticancer therapy associated with higher rates of malignant pleural effusion control in people with pharmacologically sensitive tumors? A retrospective analysis of prospectively Collected Data. Chest. 2021;160(5):1915–24. https://doi.org/10.1016/j.chest.2021.05.027CrossRefPubMed

29.

Kawashima Y, Fukuhara T, Saito H, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, et al. Bevacizumab plus Erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. The Lancet Respiratory Medicine. 2022;10(1):72–82. https://doi.org/10.1016/s2213-2600(21)00166-1CrossRefPubMed

30.

Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, et al. ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2013;31(31):3926–34. https://doi.org/10.1200/jco.2012.47.3983CrossRefPubMed

31.

Jayson GC, Kerbel R, Ellis LM, Harris AL. Antiangiogenic therapy in oncology: current status and future directions. Lancet. 2016;388(10043):518–29. https://doi.org/10.1016/s0140-6736(15)01088-0CrossRefPubMed

32.

Tamiya M, Tamiya A, Suzuki H, Taniguchi Y, Katayama K, Minomo S, Nakao K, Takeuchi N, Matsuda Y, Naito Y, et al. Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab-paclitaxel for non-squamous non-small cell lung cancer with malignant pleural effusion. Invest New Drugs. 2021;39(4):1106–12. https://doi.org/10.1007/s10637-021-01076-8CrossRefPubMed

33.

Socinski MA, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, Thomas CA, et al. IMpower150 final overall survival analyses for Atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous NSCLC. J Thorac Oncol. 2021;16(11):1909–24. https://doi.org/10.1016/j.jtho.2021.07.009CrossRefPubMed

34.

Nogami N, Barlesi F, Socinski MA, Reck M, Thomas CA, Cappuzzo F, Mok TSK, Finley G, Aerts JG, Orlandi F, et al. IMpower150 final exploratory analyses for Atezolizumab plus bevacizumab and chemotherapy in key NSCLC patient subgroups with EGFR mutations or metastases in the liver or brain. J Thorac Oncol. 2022;17(2):309–23. https://doi.org/10.1016/j.jtho.2021.09.014 CrossRefPubMed

35.

Chen WT, Lin YH, Changchien CY, Chen Y, Chang HH, Tsai WC, Tsai HC, Wang CY, Shen MS, Cheng LT, et al. Concurrent blockade of endothelial EGFR and VEGF signaling on malignant associated pleural fluid induced angiogenesis: from clinic to bench. Biomedicines. 2021;9(10). https://doi.org/10.3390/biomedicines9101327

36.

Larsen AK, Ouaret D, El Ouadrani K, Petitprez A. Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacol Ther. 2011;131(1):80–90. https://doi.org/10.1016/j.pharmthera.2011.03.012CrossRefPubMed

37.

Watanabe H, Ichihara E, Kayatani H, Makimoto G, Ninomiya K, Nishii K, Higo H, Ando C, Okawa S, Nakasuka T, et al. VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers. Cancer Sci. 2021;112(5):1853–64. https://doi.org/10.1111/cas.14801CrossRefPubMedPubMedCentral

38.

Le X, Nilsson M, Goldman J, Reck M, Nakagawa K, Kato T, Ares LP, Frimodt-Moller B, Wolff K, Visseren-Grul C, et al. Dual EGFR-VEGF pathway inhibition: a promising strategy for patients with EGFR-mutant NSCLC. J Thorac Oncol. 2021;16(2):205–15. https://doi.org/10.1016/j.jtho.2020.10.006CrossRefPubMed

39.

West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ, Kopp HG, Daniel D, McCune S, Mekhail T, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):924–37. https://doi.org/10.1016/s1470-2045(19)30167-6CrossRefPubMed

Title: Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion
Authors: Hao Zeng
Yuanyuan Zhang
Sihan Tan
Qin Huang
Xin Pu
Panwen Tian
Yalun Li
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Bevacizumab
NSCLC
NSCLC
Pleural Effusion
Pleurodesis
Published in: BMC Pulmonary Medicine / Issue 1/2024
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-024-02886-1

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2024

Incidence of noninvasive ventilation failure and mortality in patients with acute respiratory distress syndrome: a systematic review and proportion meta-analysis

Welding fume exposure and prevalence of chronic respiratory symptoms among welders in micro- and small-scale enterprise in Akaki Kality sub-city, Addis Ababa, Ethiopia: a comparative cross-sectional study

Treatment of malignant airway obstruction with Y-shape sigma stent loaded with I125 seeds installed via rigid bronchoscopy

Retraction Note: Serum bilirubin levels in primary Sjögren’s syndrome: an association with interstitial lung disease

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study

Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials