Safety and Feasibility of Carboplatin and Paclitaxel in Combination with Nintedanib for Non-small Cell Lung Cancer Patients with Idiopathic Pulmonary Fibrosis: a Prospective Pilot Study

Overview

Journal Transl Lung Cancer Res

Date 2023 May 17

PMID 37197621

Authors

Tomonori Makiguchi

Hisashi Tanaka

Koichi Okudera

Kageaki Taima

Sadatomo Tasaka

Affiliations

Soon will be listed here.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a risk factor for mortality in patients with lung cancer. Nintedanib has been known to slow down the decline of lung function and reduce IPF exacerbation. We aimed to explore the feasibility of adding nintedanib to chemotherapy for non-small cell lung cancer (NSCLC) patients with IPF.

Methods: Chemotherapy-naïve stage III or IV NSCLC patients with IPF were prospectively enrolled and received carboplatin plus paclitaxel with nintedanib. Primary endpoint was incidence of treatment-related acute exacerbation of IPF within 8 weeks after the last administration of chemotherapy. We initially planned to enroll 30 patients and consider it feasible when the incident rate is less than 10%. Secondary endpoint was progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR).

Results: After 27 patients were enrolled, trial was early terminated because 4 patients (14.8%) experienced exacerbation. Median PFS and OS were 5.4 months [95% confidence interval (CI): 4.6-9.3] and 15.8 months (95% CI: 12.2-30.1), respectively. ORR and DCR were 40.7% (95% CI: 24.5-59.2%) and 88.9% (95% CI: 71.9-96.1%), respectively. One patient discontinued trial treatment due to neuropathy.

Conclusions: Although the primary endpoint was not met, there might be a survival benefit. The addition of nintedanib to chemotherapy might be useful in selected population.

Citing Articles

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Chen H, Xu X, Li J, Xue Y, Li X, Zhang K Front Pharmacol. 2024; 15:1491400.

PMID: 39534084 PMC: 11555290. DOI: 10.3389/fphar.2024.1491400.

References

du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N . Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2015; 17(1):78-89. DOI: 10.1016/S1470-2045(15)00366-6. View

Sekine A, Satoh H, Baba T, Ikeda S, Okuda R, Shinohara T . Safety and efficacy of S-1 in combination with carboplatin in non-small cell lung cancer patients with interstitial lung disease: a pilot study. Cancer Chemother Pharmacol. 2016; 77(6):1245-52. DOI: 10.1007/s00280-016-3040-8. View

Hanna N, Kaiser R, Sullivan R, Aren O, Ahn M, Tiangco B . Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial. Lung Cancer. 2016; 102:65-73. DOI: 10.1016/j.lungcan.2016.10.011. View

Minegishi Y, Sudoh J, Kuribayasi H, Mizutani H, Seike M, Azuma A . The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias. Lung Cancer. 2010; 71(1):70-4. DOI: 10.1016/j.lungcan.2010.04.014. View

Jiang L, Wang Y, Peng Q, Shu X, Wang G, Wu X . Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody. Clin Rheumatol. 2019; 38(6):1655-1663. DOI: 10.1007/s10067-019-04457-w. View

Khalil N, Parekh T, OConnor R, Antman N, Kepron W, Yehaulaeshet T . Regulation of the effects of TGF-beta 1 by activation of latent TGF-beta 1 and differential expression of TGF-beta receptors (T beta R-I and T beta R-II) in idiopathic pulmonary fibrosis. Thorax. 2001; 56(12):907-15. PMC: 1745982. DOI: 10.1136/thorax.56.12.907. View

Hilberg F, Roth G, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U . BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008; 68(12):4774-82. DOI: 10.1158/0008-5472.CAN-07-6307. View

Richeldi L, du Bois R, Raghu G, Azuma A, Brown K, Costabel U . Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370(22):2071-82. DOI: 10.1056/NEJMoa1402584. View

Homma S, Suda T, Hongo Y, Yoshida M, Hiroi S, Iwasaki K . Incidence and changes in treatment of acute exacerbation of idiopathic pulmonary fibrosis in Japan: A claims-based retrospective study. Respir Investig. 2022; 60(6):798-805. DOI: 10.1016/j.resinv.2022.07.004. View

10.

Shiratori T, Tanaka H, Tabe C, Tsuchiya J, Ishioka Y, Itoga M . Effect of nintedanib on non-small cell lung cancer in a patient with idiopathic pulmonary fibrosis: A case report and literature review. Thorac Cancer. 2020; 11(6):1720-1723. PMC: 7262881. DOI: 10.1111/1759-7714.13437. View

11.

Raghu G, Remy-Jardin M, Myers J, Richeldi L, Ryerson C, Lederer D . Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018; 198(5):e44-e68. DOI: 10.1164/rccm.201807-1255ST. View

12.

Reck M, Kaiser R, Mellemgaard A, Douillard J, Orlov S, Krzakowski M . Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014; 15(2):143-55. DOI: 10.1016/S1470-2045(13)70586-2. View

13.

Kenmotsu H, Yoh K, Mori K, Ono A, Baba T, Fujiwara Y . Phase II study of nab-paclitaxel + carboplatin for patients with non-small-cell lung cancer and interstitial lung disease. Cancer Sci. 2019; 110(12):3738-3745. PMC: 6890441. DOI: 10.1111/cas.14217. View

14.

Otsubo K, Kishimoto J, Ando M, Kenmotsu H, Minegishi Y, Horinouchi H . Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial. Eur Respir J. 2022; 60(6). DOI: 10.1183/13993003.00380-2022. View

15.

Mei Q, Liu Z, Zuo H, Yang Z, Qu J . Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis. Front Pharmacol. 2022; 12:797292. PMC: 8807692. DOI: 10.3389/fphar.2021.797292. View

16.

Kewalramani N, Machahua C, Poletti V, Cadranel J, Wells A, Funke-Chambour M . Lung cancer in patients with fibrosing interstitial lung diseases: an overview of current knowledge and challenges. ERJ Open Res. 2022; 8(2). PMC: 9209850. DOI: 10.1183/23120541.00115-2022. View

17.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

18.

Flaherty K, Wells A, Cottin V, Devaraj A, Walsh S, Inoue Y . Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019; 381(18):1718-1727. DOI: 10.1056/NEJMoa1908681. View

19.

Asahina H, Oizumi S, Takamura K, Harada T, Harada M, Yokouchi H . A prospective phase II study of carboplatin and nab-paclitaxel in patients with advanced non-small cell lung cancer and concomitant interstitial lung disease (HOT1302). Lung Cancer. 2019; 138:65-71. DOI: 10.1016/j.lungcan.2019.09.020. View