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Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC.
Jpn J Clin Oncol 2012; 42(6):528-33JJ

Abstract

OBJECTIVE

Somatic mutations in the epidermal growth factor receptor gene are associated with a therapeutic response to epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib in patients with non-small cell lung cancer. Although the safety profile of these drugs is favorable, a small proportion of patients with EGFR mutation-positive non-small cell lung cancer must discontinue treatment because of adverse events such as interstitial lung disease and hepatotoxicity. Subsequent chemotherapy has not been optimized in such patients.

METHODS

We performed a retrospective analysis of EGFR mutation-positive non-small cell lung cancer patients who received both gefitinib and erlotinib at our institution. Patients received the second epidermal growth factor receptor-tyrosine kinase inhibitor after experiencing an adverse event or progressive disease on the first epidermal growth factor receptor-tyrosine kinase inhibitor.

RESULTS

We identified 14 patients who received both gefitinib and erlotinib in the course of their treatment. Three patients initially treated with gefitinib and two with erlotinib discontinued epidermal growth factor receptor-tyrosine kinase inhibitor therapy because of severe non-hematologic toxicity (one because of gefitinib-induced interstitial lung disease, one because of erlotinib-induced lupus erythematosus-like eruption and three because of hepatotoxicity). All five of these patients were able successfully to continue therapy with the second epidermal growth factor receptor-tyrosine kinase inhibitor with no evidence of a recurrent adverse event. Progression-free survival was significantly longer in these five patients than in the nine patients who discontinued treatment with the first epidermal growth factor receptor-tyrosine kinase inhibitor because of disease progression.

CONCLUSIONS

EGFR mutation-positive non-small cell lung cancer patients who discontinue treatment with a first epidermal growth factor receptor-tyrosine kinase inhibitor because of an adverse event benefit substantially from switching to a second epidermal growth factor receptor-tyrosine kinase inhibitor before the development of drug resistance.

Authors+Show Affiliations

Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, Japan. chi-okamoto@dotd.med.kindai.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22457323

Citation

Takeda, Masayuki, et al. "Clinical Impact of Switching to a Second EGFR-TKI After a Severe AE Related to a First EGFR-TKI in EGFR-mutated NSCLC." Japanese Journal of Clinical Oncology, vol. 42, no. 6, 2012, pp. 528-33.
Takeda M, Okamoto I, Tsurutani J, et al. Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC. Jpn J Clin Oncol. 2012;42(6):528-33.
Takeda, M., Okamoto, I., Tsurutani, J., Oiso, N., Kawada, A., & Nakagawa, K. (2012). Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC. Japanese Journal of Clinical Oncology, 42(6), pp. 528-33. doi:10.1093/jjco/hys042.
Takeda M, et al. Clinical Impact of Switching to a Second EGFR-TKI After a Severe AE Related to a First EGFR-TKI in EGFR-mutated NSCLC. Jpn J Clin Oncol. 2012;42(6):528-33. PubMed PMID: 22457323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC. AU - Takeda,Masayuki, AU - Okamoto,Isamu, AU - Tsurutani,Junji, AU - Oiso,Naoki, AU - Kawada,Akira, AU - Nakagawa,Kazuhiko, Y1 - 2012/03/28/ PY - 2012/3/30/entrez PY - 2012/3/30/pubmed PY - 2012/7/25/medline SP - 528 EP - 33 JF - Japanese journal of clinical oncology JO - Jpn. J. Clin. Oncol. VL - 42 IS - 6 N2 - OBJECTIVE: Somatic mutations in the epidermal growth factor receptor gene are associated with a therapeutic response to epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib in patients with non-small cell lung cancer. Although the safety profile of these drugs is favorable, a small proportion of patients with EGFR mutation-positive non-small cell lung cancer must discontinue treatment because of adverse events such as interstitial lung disease and hepatotoxicity. Subsequent chemotherapy has not been optimized in such patients. METHODS: We performed a retrospective analysis of EGFR mutation-positive non-small cell lung cancer patients who received both gefitinib and erlotinib at our institution. Patients received the second epidermal growth factor receptor-tyrosine kinase inhibitor after experiencing an adverse event or progressive disease on the first epidermal growth factor receptor-tyrosine kinase inhibitor. RESULTS: We identified 14 patients who received both gefitinib and erlotinib in the course of their treatment. Three patients initially treated with gefitinib and two with erlotinib discontinued epidermal growth factor receptor-tyrosine kinase inhibitor therapy because of severe non-hematologic toxicity (one because of gefitinib-induced interstitial lung disease, one because of erlotinib-induced lupus erythematosus-like eruption and three because of hepatotoxicity). All five of these patients were able successfully to continue therapy with the second epidermal growth factor receptor-tyrosine kinase inhibitor with no evidence of a recurrent adverse event. Progression-free survival was significantly longer in these five patients than in the nine patients who discontinued treatment with the first epidermal growth factor receptor-tyrosine kinase inhibitor because of disease progression. CONCLUSIONS: EGFR mutation-positive non-small cell lung cancer patients who discontinue treatment with a first epidermal growth factor receptor-tyrosine kinase inhibitor because of an adverse event benefit substantially from switching to a second epidermal growth factor receptor-tyrosine kinase inhibitor before the development of drug resistance. SN - 1465-3621 UR - https://www.unboundmedicine.com/medline/citation/22457323/Clinical_impact_of_switching_to_a_second_EGFR_TKI_after_a_severe_AE_related_to_a_first_EGFR_TKI_in_EGFR_mutated_NSCLC_ L2 - https://academic.oup.com/jjco/article-lookup/doi/10.1093/jjco/hys042 DB - PRIME DP - Unbound Medicine ER -