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Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101).
Oncologist. 2020 Jul 12 [Online ahead of print]O

Abstract

LESSONS LEARNED

This phase II trial evaluated the efficacy of erlotinib for patients with non-small cell lung cancer with leptomeningeal metastasis. The 17 cerebrospinal fluid specimens that were available for epidermal growth factor receptor mutation analysis were all negative for the resistance-conferring T790M mutation. The cytological objective clearance rate was 30.0% (95% confidence interval: 11.9%-54.3%). The median time to progression was 2.2 months. The rate of cerebrospinal fluid penetration among these patients was equivalent to those in previous reports regarding leptomeningeal metastasis.

BACKGROUND

Leptomeningeal metastases (LM) occur in approximately 5% of patients with non-small cell lung cancer (NSCLC) and are associated with a poor prognosis. However, no prospective study has identified an active chemotherapeutic drug in this setting.

METHODS

Patients were considered eligible to receive erlotinib if they had NSCLC with cytologically confirmed LM. The objective cytological clearance rate, time to LM progression (TTP), overall survival (OS), quality of life outcomes, and pharmacokinetics were analyzed. This study was closed because of slow accrual at 21 of the intended 32 patients (66%).

RESULTS

Between December 2011 and May 2015, 21 patients (17 with activating epidermal growth factor receptor [EGFR] mutations) were enrolled. The 17 cerebrospinal fluid specimens available were all negative for the T790M mutation, which confers erlotinib resistance. The clearance rate was 30.0% (95% confidence interval [CI]: 11.9%-54.3%), the median TTP was 2.2 months, and the median OS was 3.4 months. Significantly longer TTP and OS times were observed in patients with mutant EGFR (p = .0054 and p < .0001, respectively). The mean cerebrospinal fluid penetration rate was 3.31% ± 0.77%. There was a good correlation between plasma and cerebrospinal fluid (CSF) concentrations, although there was no clear correlation between pharmacokinetic parameters and clinical outcome.

CONCLUSION

Erlotinib was active for LM and may be a treatment option for patients with EGFR-mutated NSCLC and LM.

Authors+Show Affiliations

Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.Department of Biostatistics, Yokohama City University, Yokohama, Japan.Division of Molecular Pharmacology and Pharmacokinetics, National Cancer Center Research Institute, Tokyo, Japan.Department of Respiratory Disease, National Hospital Organization Fukuoka-Higashi Medical Center, Koga, Japan.Department of Respiratory Medicine, Japan Community Health Care Organization (JCHO) Kyushu Hospital, Kitakyushu, Japan.Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan.Department of Respiratory Disease, Japan Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.Department of Respiratory Oncology, Iizuka Hospital, Iizuka, Japan.Clinical Research Support Center Kyushu, Fukuoka, Japan.Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. Department of Thoracic and Breast Surgery, Oita University, Yufu, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32654250

Citation

Nosaki, Kaname, et al. "Erlotinib for Non-Small Cell Lung Cancer With Leptomeningeal Metastases: a Phase II Study (LOGIK1101)." The Oncologist, 2020.
Nosaki K, Yamanaka T, Hamada A, et al. Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101). Oncologist. 2020.
Nosaki, K., Yamanaka, T., Hamada, A., Shiraishi, Y., Harada, T., Himeji, D., Kitazaki, T., Ebi, N., Shimose, T., Seto, T., Takenoyama, M., & Sugio, K. (2020). Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101). The Oncologist. https://doi.org/10.1634/theoncologist.2020-0640
Nosaki K, et al. Erlotinib for Non-Small Cell Lung Cancer With Leptomeningeal Metastases: a Phase II Study (LOGIK1101). Oncologist. 2020 Jul 12; PubMed PMID: 32654250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101). AU - Nosaki,Kaname, AU - Yamanaka,Takeharu, AU - Hamada,Akinobu, AU - Shiraishi,Yoshimasa, AU - Harada,Taishi, AU - Himeji,Daisuke, AU - Kitazaki,Takeshi, AU - Ebi,Noriyuki, AU - Shimose,Takayuki, AU - Seto,Takashi, AU - Takenoyama,Mitsuhiro, AU - Sugio,Kenji, Y1 - 2020/07/12/ PY - 2020/06/30/received PY - 2020/7/13/entrez PY - 2020/7/13/pubmed PY - 2020/7/13/medline JF - The oncologist JO - Oncologist N2 - LESSONS LEARNED: This phase II trial evaluated the efficacy of erlotinib for patients with non-small cell lung cancer with leptomeningeal metastasis. The 17 cerebrospinal fluid specimens that were available for epidermal growth factor receptor mutation analysis were all negative for the resistance-conferring T790M mutation. The cytological objective clearance rate was 30.0% (95% confidence interval: 11.9%-54.3%). The median time to progression was 2.2 months. The rate of cerebrospinal fluid penetration among these patients was equivalent to those in previous reports regarding leptomeningeal metastasis. BACKGROUND: Leptomeningeal metastases (LM) occur in approximately 5% of patients with non-small cell lung cancer (NSCLC) and are associated with a poor prognosis. However, no prospective study has identified an active chemotherapeutic drug in this setting. METHODS: Patients were considered eligible to receive erlotinib if they had NSCLC with cytologically confirmed LM. The objective cytological clearance rate, time to LM progression (TTP), overall survival (OS), quality of life outcomes, and pharmacokinetics were analyzed. This study was closed because of slow accrual at 21 of the intended 32 patients (66%). RESULTS: Between December 2011 and May 2015, 21 patients (17 with activating epidermal growth factor receptor [EGFR] mutations) were enrolled. The 17 cerebrospinal fluid specimens available were all negative for the T790M mutation, which confers erlotinib resistance. The clearance rate was 30.0% (95% confidence interval [CI]: 11.9%-54.3%), the median TTP was 2.2 months, and the median OS was 3.4 months. Significantly longer TTP and OS times were observed in patients with mutant EGFR (p = .0054 and p < .0001, respectively). The mean cerebrospinal fluid penetration rate was 3.31% ± 0.77%. There was a good correlation between plasma and cerebrospinal fluid (CSF) concentrations, although there was no clear correlation between pharmacokinetic parameters and clinical outcome. CONCLUSION: Erlotinib was active for LM and may be a treatment option for patients with EGFR-mutated NSCLC and LM. SN - 1549-490X UR - https://www.unboundmedicine.com/medline/citation/32654250/Erlotinib_for_Non-Small_Cell_Lung_Cancer_with_Leptomeningeal_Metastases:_A_Phase_II_Study_(LOGIK1101) L2 - https://doi.org/10.1634/theoncologist.2020-0640 DB - PRIME DP - Unbound Medicine ER -
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