Abstract
Purpose
Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.
Methods
We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.
Results
EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone.
Conclusions
EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.
Similar content being viewed by others
Abbreviations
- CS:
-
Corticosteroid
- EGFR:
-
Epidermal growth factor receptor
- DAD:
-
Diffuse alveolar damage
- HRCT:
-
High-resolution computed tomography
- ILD:
-
Interstitial lung disease
- NSCLC:
-
Non-small cell lung cancer
- OS:
-
Overall survival
- PFS:
-
Progression-free survival
- PS:
-
Performance status
- PSL:
-
Prednisolone
- TKI:
-
Tyrosine kinase inhibitor
References
Mok TS, Wu YL, Thongprasert S et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957
Mitsudomi T, Morita S, Yatabe Y et al West Japan Oncology Group (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11:121–128
Maemondo M, Inoue A, Kobayashi K et al North-East Japan Study Group (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388
Zhou C, Wu YL, Chen G et al (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12:735–742
Rosell R, Carcereny E, Gervais R et al Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246
Ando M, Okamoto I, Yamamoto N et al (2006) Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 24:2549–2556
Gemma A, Kudoh S, Ando M et al (2014) Final safety and efficacy of erlotinib in the phase 4 POLARSTAR surveillance study of 10708 Japanese patients with non-small-cell lung cancer. Cancer Sci 105:1584–1590
Fukui T, Otani S, Hataishi R et al (2010) Successful rechallenge with erlotinib in a patient with EGFR-mutant lung adenocarcinoma who developed gefitinib-related interstitial lung disease. Cancer Chemother Pharmacol 65:803–806
Chang SC, Chang CY, Chen CY et al (2010) Successful erlotinib rechallenge after gefitinib-induced acute interstitial pneumonia. J Thorac Oncol 5:1105–1106
Tian Q, Chen LA (2011) Erlotinib achieved partial response in a non-small cell lung cancer patient with gefitinib-induced interstitial lung disease. Case Rep Oncol 4:464–466
Dallas JL, Jantz MA, Lightsey JL et al (2011) Successful erlotinib rechallenge after erlotinib-induced interstitial lung disease. J Thorac Oncol 6:1142–1143
Togashi Y, Masago K, Hamatani Y et al (2012) Successful erlotinib rechallenge for leptomeningeal metastases of lung adenocarcinoma after erlotinib-induced interstitial lung disease: a case report and review of the literature. Lung Cancer 77:464–468
Takeda M, Okamoto I, Makimura C et al (2010) Successful treatment with erlotinib after gefitinib-induced severe interstitial lung disease. J Thorac Oncol 5:1103–1104
Arakawa N, Tsujita A, Saito N et al (2013) Successful erlotinib rechallenge after both gefitinib- and erlotinib-induced interstitial lung diseases. Respirol Case Rep 1:17–19
Nakamichi S, Kubota K, Horinouchi H et al (2013) Successful EGFR-TKI rechallenge of leptomeningeal carcinomatosis after gefitinib-induced interstitial lung disease. Jpn J Clin Oncol 43:422–425
Takamochi K, Suzuki K, Bashar AH et al (2007) Readministration of gefitinib in a responder after treatment discontinuation due to gefinitib-related interstitial lung disease: a case report. J Med Case Rep 1:138. doi:10.1186/1752-1947-1-138
Suzuki M, Asahina H, Konishi J et al (2008) Recurrent gefitinib-induced interstitial lung disease. Intern Med 47:533–536
Camus P, Kudoh S, Ebina M (2004) Interstitial lung disease associated with drug therapy. Br J Cancer 2:S18–S23
Schwaiblmair M, Behr W, Haeckel T et al (2012) Drug induced interstitial lung disease. Open Respir Med J 6:63–74
Müller NL, White DA, Jiang H et al (2004) Diagnosis and management of drug-associated interstitial lung disease. Br J Cancer 91:S24–S30
Hyzy R, Huang S, Myers J et al (2007) Acute exacerbation of idiopathic pulmonary fibrosis. Chest 132:1652–1658
Higenbottam T, Kuwano K, Nemery B et al (2004) Understanding the mechanisms of drug-associated interstitial lung disease. Br J Cancer 91:S31–S37
NSCLC Meta-Analyses Collaborative Group (2008) Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 26:4617–4625
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors have no conflicts of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. A signed informed consent was obtained from all individual participants included in the study (five patients who received EGFR-TKI rechallenge).
Funding
No funding for this work was received.
Rights and permissions
About this article
Cite this article
Kashiwabara, K., Semba, H., Fujii, S. et al. Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease. Cancer Chemother Pharmacol 79, 705–710 (2017). https://doi.org/10.1007/s00280-017-3261-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-017-3261-5