Results from the phase 2 OCEAN trial show that osimertinib is effective in treating central nervous system metastases from non–small cell lung cancer in patients with certain mutations.
Osimertinib (Tagrisso) was shown to be a durable treatment for patients with central nervous system (CNS) metastasis who had non-small cell lung cancer (NSCLC) tumors that harbored EGFR T790M mutations, according to study results published in the Journal of Thoracic Oncology.1
The OCEAN study (NCT03769103) was a phase 2, 2-cohort study that looked at 66 patients with NSCLC. In the first cohort, 40 patients with tumors that harbored EGFR T790M mutations were observed versus those on first-line treatment. All 66 patients had radiation therapy (RT) naive CNS metastasis from sensitizing EGFR-mutations, 78% of patients had multiple CNS metastases. The primary endpoint of the study was brain metastasis response rate (BMRR), according to the PAREXEL criteria, which researchers found was 70% among patients (n = 20) with a solid tumor.
Median brain metastasis-related progression-free survival (PFS) was 66.7% (90% CI, 54.3%-79.1%), median overall survival (OS) was 25.2 months, overall response rate (ORR) was 40.5%, and median PFS was 7.1 months. Moreover, brain metastasis-related PFS in patients with EGFR exon 19 deletion was significantly longer in comparison to those with exon 21 L858R at a median 31.8 months versus 8.3 months (P = 0.032), respectively. Blood trough concentration at day 22 was not correlated to the efficacy of osimertinib against CNS metastasis with the median trough blood and cerebrospinal fluid concentrations of osimertinib were 568 nM and 4.10 nM, respectively.
“This study is valuable because it evaluated the true antitumor effects of osimertinib alone for previously untreated CNS metastasis, whereas [previous studies] were subgroup analyses and included patients who had previously been treated with RT,” the researchers wrote in their analysis. “In addition, the BMRR achieved in this study was comparable with those found in the previous studies.”
Overall, the BMRR was 66.7% (90% CI, 54.3%-79.1%) with the best overall responses with complete response (CR) was equal to 4, partial response (PR) was equal to 22, and stable disease was equal to 8. One-year and 2-year survival rates were at 61.9% and 52% of patients, respectively, and overall tumor response was 40.5% (95% CI, 24.7%-57.9%) according to RECIST criteria. The best overall responses, according to RECIST criteria, was a CR equal to 0, PR equal to 15, stable disease equal to 12, and partial disease equal to 9.
“Median brain metastasis-related PFS was a promising 25.2 months and better than OS owing to the effect of osimertinib and partly the increase in censored cases who developed extracranial progression,” the researchers explained. “Or the CNS lesions may have underexposure tumor to previous EGFR TKIs compared with extracranial and resulted in a higher response and a longer brain metastasis-related PFS than systemic PFS.”
Adverse events (AEs) experienced by patients included grade 3 or 4 leukopenia and neutropenia observed in 4 patients. Seventy-two percent of patients experienced anemia of any grade with 60% experiencing leukopenia, 45% with neutropenia, 30% with AST increased, and 35% experienced with rash acneiform. One patient experienced grade 3/4 thrombocytopenia and one other patient experienced grade 3/4 pneumonitis. According to the researchers, there was no treatment-related adverse events.
“In conclusion, the OCEAN study was the first to evaluate the efficacy of osimertinib against RT-naive CNS metastasis from T790M-positive NSCLC,” the researchers concluded. “The primary end point was met, and the results revealed the efficacy of osimertinib in patients with CNS metastasis harboring EGFR T790M mutations especially for EGFR-sensitizing mutation of 19-del.”
Yamaguchi H, Wakuda K, Fukuda M, et al. A phase II study of osimertinib for radiotherapy-naive central nervous system metastasis from NSCLC: Results for the T790M Cohort of the OCEAN Study (LOGIK1603/WJOG9116L). J Thorac Oncol. 2021;16(12):2121-2132. doi: 10.1016/j.jtho.2021.07.026