Erlotinib for Non-Small Cell Lung Cancer with Leptomeningeal Metastases: A Phase II Study (LOGIK1101).

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 = .0113 and p < .0054, 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: Kaname Nosaki, Takeharu Yamanaka, Akinobu Hamada, Yoshimasa Shiraishi, Taishi Harada, Daisuke Himeji, Takeshi Kitazaki, Noriyuki Ebi, Takayuki Shimose, Takashi Seto, Mitsuhiro Takenoyama, Kenji Sugio
• Journal: The oncologist (Oncologist) Vol. 25 Issue 12 Pg. e1869-e1878 (12 2020) ISSN: 1549-490X [Electronic] England
• PMID: 32654250 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

Chemical References

• Protein Kinase Inhibitors
• Erlotinib Hydrochloride
• ErbB Receptors

Topics

• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• ErbB Receptors (genetics)
• Erlotinib Hydrochloride (therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Quality of Life