Negative impact of malignant effusion on osimertinib treatment for non-small cell lung cancer harboring EGFR mutation

• Published in: Investigational new drugs Vol. 38; no. 1; pp. 194 - 201
• Main Authors: Kawamura, Takahisa, Kenmotsu, Hirotsugu, Kobayashi, Haruki, Omori, Shota, Nakashima, Kazuhisa, Wakuda, Kazushige, Ono, Akira, Naito, Tateaki, Murakami, Haruyasu, Mori, Keita, Endo, Masahiro, Takahashi, Toshiaki
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2020; Springer Nature B.V
• Subjects: Acrylamides - adverse effects; Adult; Aged; Aged, 80 and over; Aniline Compounds - adverse effects; Antineoplastic Agents - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cerebrospinal fluid; Confidence intervals; Drug Resistance, Neoplasm; Effectiveness; Effusion; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; Female; Follow-Up Studies; Growth factors; Humans; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical treatment; Medicine; Medicine & Public Health; Middle Aged; Mutation; Non-small cell lung carcinoma; Oncology; Pharmacology/Toxicology; Pleural Effusion, Malignant - chemically induced; Pleural Effusion, Malignant - genetics; Pleural Effusion, Malignant - pathology; Prognosis; Protein-tyrosine kinase; Retrospective Studies; Short Report; Studies; Survival Rate; Targeted cancer therapy; Tyrosine; Osimertinib; EGFR-TKI; Malignant effusion; Non-small cell lung cancer
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-019-00808-1

Summary 3rd-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, have reasonable efficacy in non–small-cell lung cancers (NSCLC) with EGFR mutations. However, the efficacy of osimertinib in NSCLC patients with fluids, such as pleural, pericardial and abdominal effusions, is unclear. We evaluated the efficacy of osimertinib in this specific setting. NSCLC patients harboring EGFR T790 M mutations who experienced progressive disease after first EGFR-TKI treatment and started osimertinib treatment between April 2016 and August 2018 were retrospectively screened. In particular, we assessed the efficacy of osimertinib for NSCLC with EGFR T790 M mutations in patients who were diagnosed with EGFR T790 M mutation by malignant effusion. Among 90 patients with EGFR T790 M mutation who started osimertinib treatment after EGFR-TKI failure, 21 were diagnosed from malignant effusions excluding cerebrospinal fluid (F group) and 69 using other methods including tissue biopsies (NF group). Patient characteristics were well-balanced between the two groups. Overall response was 50%, and significantly worse in the F group (29%) than the NF group (57%; P  = 0.025). Median progression-free survival with osimertinib treatment in the F group (7.1 months, 95% confidence interval [CI]: 2.3–14.0) was significantly shorter than that in the NF group (11.9 months, 95% CI: 9.5–16.0; P  = 0.046)). Median drainage-free time was 10.9 months (95% CI: 1.4 months– not reached). The present study showed that the efficacy of osimertinib for NSCLC in which EGFR T790 M mutation is detected by malignant effusion may be less than in EGFR T790 M-mutated NSCLC detected by other methods.