Osimertinib Prevents CNS Progression in Advanced NSCLC in a Real-World Setting

Patients with advanced non—small cell lung cancer (NSCLC) and baseline central nervous system (CNS) metastasis showed control of their CNS metastasis after receiving osimertinib (Tagrisso) in a real-world clinical setting, according to findings presented in a poster at the 2018 European Lung Cancer Conference, held April 11-14 in Geneva, Switzerland.¹

Additionally, patients who experienced local disease progression did not show progression in the CNS with osimertinib.

CNS clinical benefit was observed in 7 patients with brain metastasis at baseline with osimertinib; the objective response rate (ORR) by RECIST was 70%, including partial responses in 50% and stable disease in 20%. The 30% of patients with progressive disease showed progression of local tumor lesions.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that selectively inhibits both EGFR TKI—sensitizing and EGFR T790M resistance mutations and has the ability to penetrate the blood-brain barrier, which has led to efficacy with CNS metastasis, according to results from the phase III FLAURA trial.² The FLAURA study investigated osimertinib compared with standard-of-care EGFR TKIs, including gefitinib (Iressa) or erlotinib (Tarceva) in patients with EGFR-mutant NSCLC with or without CNS metastasis.

“EGFR driver mutations occur in about 10% of patients [with NSCLC]; osimertinib has activity in EGFR-mutated advanced lung adenocarcinoma. Particularly, osimertinib showed a good penetration through the blood-brain barrier and efficacy in CNS metastases,” explained Rok Devjak, MD, PhD, of the Department of Clinical Medicine, Institute of Oncology, Ljubljana in Ljubljana, SIovakia.

Together with colleagues, Devjak conducted this single-center, retrospective study that assessed the course of CNS disease in patients with EGFR-mutant advanced NSCLC in a real-world clinical setting.

The study included 23 patients who were treated with osimertinib following progression on an EGFR TKI and 2 patients who received osimertinib in the first line at 80 mg daily. The median age of the 25 patients was 67 (range, 55-82) and 84% of the patients were female.

CT or MRI scans were done prior to treatment to confirm the presence of CNS metastases and responses were evaluated radiologically every 8 to 16 weeks according to RECIST criteria. All patients had at least 1 evaluation during the treatment duration from October 2015 through November 2017.

The maximum duration of osimertinib treatment was 46 weeks for patients with CNS metastasis and 56 weeks for those without CNS metastases. Median treatment duration at the time of analysis was 27 weeks with 11 patients remaining on osimertinib. The investigators also recorded the line of treatment on osimertinib, previous treatment received for CNS metastases, efficacy, and the date of progression.

“There was no isolated CNS progression during osimertinib treatment observed among all 25 analyzed patients,” Devjak commented to OncLive. “The key point was that all progression was in localized lesions, not in the CNS. Usually we use osimertinib in the second line per recommendations. However, these data suggest that osimertinib should be given upfront to patients with CNS metastasis.”

Prior to osimertinib treatment, 10 patients (40%) had CNS metastases to the brain only. Of these, 4 patients had received prior CNS treatment of radiotherapy or surgery.

“Osimertinib had comparable CNS efficacy to clinical trial results in our real-world analysis, and no CNS only progressive disease was observed,” he said. The investigators are preparing a publication of these data plus data in patients without CNS metastasis participating in this and a second study, with a total of 50 patients.

References

1. Devjak R, Turnsek Hitij N, Mohorcic K, Rajer M, Cufer T. CNS response to osimertinib in patients with EGFR mutated lung adenocarcinoma: Real world data. Presented at: 2018 European Lung Cancer Congress; April 11-14, 2018; Geneva, Switzerland. Abstract 154P.
2. Vansteenkiste J, Reungwetwattana T, Nakagawa K, et al. CNS Response to Osimertinib Vs. Standard-of-Care EGFR-TKI as First-Line Treatment in Patients with EGFRm Advanced NSCLC: FLAURA. Presented at ESMO Asia 2017 Congress; November 17-19, 2017; Singapore. Abstract LBA5.