Osimertinib Extends Progression-Free Survival in EGFR T790M–Positive Lung Cancer with CNS Metastases
Chicago, IL—Osimertinib (Tagrisso) extends progression-free survival (PFS) compared with standard chemotherapy in patients with EGFR T790M mutation–positive non–small-cell lung cancer (NSCLC) who have central nervous system (CNS) metastases, reported Marina C. Garassino, MD, Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, at the 2017 ASCO annual meeting.
A prespecified subgroup analysis of the phase 3 AURA clinical trial showed a 6.1-month improvement in PFS with osimertinib compared with platinum-based doublet chemotherapy in patients with NSCLC with CNS metastases, consistent with earlier evidence of the potential of osimertinib to penetrate the blood–brain barrier, said Dr Garassino.
“Encouraging activity [of osimertinib] was observed in patients with leptomeningeal metastasis,” said Dr Garassino.
Up to 40% of patients with EGFR-positive NSCLC may have CNS metastases over the course of their disease, she said. A CNS response rate of 54% and a CNS disease control rate of 92% were achieved with osimertinib in patients with EGFR T790M–positive NSCLC with baseline CNS metastases in an earlier pooled analysis of 2 phase 2 studies.
Subgroup Analysis of the AURA 3 Study
The AURA 3 clinical trial randomized patients to osimertinib 80 mg once daily or to standard platinum-based doublet chemotherapy as second-line therapy; patients had EGFR T790M–positive locally advanced or metastatic NSCLC and disease progression after first-line therapy with an EGFR tyrosine kinase inhibitor. Osimertinib improved PFS by 5.7 months versus standard platinum-based doublet chemotherapy (10.1 months vs 4.4 months, respectively; hazard ratio [HR], 0.30; P <.001).
The data presented at ASCO were from an analysis that focused on a subset of 116 patients with CNS metastases (28% of the overall AURA 3 patient population).
Among the patients with at least 1 measurable CNS metastasis, the overall response rate was 70% with osimertinib and 31% with chemotherapy (HR, 5.13; P = .015). The onset of response to osimertinib was seen at the first radiologic examination at 6 weeks. The median duration of response was 8.9 months in the osimertinib arm versus 5.7 months in the chemotherapy arm. The disease control rate was 93% in the osimertinib arm versus 63% in the chemotherapy arm.
CNS responses with osimertinib were observed regardless of previous brain radiotherapy status.
The median best percentage change from baseline in the CNS target lesion size was a 43% reduction in the osimertinib group and 15% in the chemotherapy group.
The median CNS PFS was 11.7 months in the osimertinib arm versus 5.6 months in the chemotherapy arm, corresponding to a 68% improvement (HR, 0.32; P = .004). This HR was the same as in the AURA 3 population without brain metastases, “suggesting that osimertinib is able to convert the prognosis of patients with brain metastases similarly to patients without brain metastases,” said Dr Garassino.
The probability of having a CNS progression event was lower with osimertinib than with chemotherapy at 3 and 6 months. The cumulative incidence of brain metastases at 3 months was 2.7% with osimertinib versus 8.2% with chemotherapy; at 6 months, the incidence rates were 11.5% versus 28.2%, respectively.
The clinical activity of osimertinib was also observed in patients with leptomeningeal metastasis at baseline who were included in the analysis; 4 of 7 patients with leptomeningeal metastasis responded to osimertinib, including 2 complete responses.