Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation–Positive Non–Small Cell Lung Cancer (BLOSSOM)

Author(s): Sehhoon Park, MD, PhD¹; Richard Baldry, BSc²; Hyun Ae Jung, MD, PhD¹; Jong-Mu Sun, MD, PhD¹; Se-Hoon Lee, MD, PhD¹; Jin Seok Ahn, MD, PhD¹; Yu Jung Kim, MD, PhD²; Youngjoo Lee, MD, PhD³; Dong-Wan Kim, MD, PhD⁴; Sang-We Kim, MD, PhD⁵; Ki Hyeong Lee, MD, PhD⁶; Won Jae Lee, MD⁷; Jung Won Choi, MD, PhD⁷; Kyuha Chong, MD, PhD⁷; Jung-Il Lee, MD, PhD⁷; So-Hyeon Gwon, BS⁸; Nak-Hoon Son, PhD⁸; Myung-Ju Ahn, MD, PhD¹

Source: https://doi.org/10.1200/JCO.24.00708

Dr. Maen Hussein's Thoughts

This is a very hard and depressing disease, but now with hope. EGFR-mutated NSCLS patients showed response to osimertinib in more than 50%, 15% complete response (CR), 15 months survival. This is promising, and maybe now we can study other TKIs in this mets.

PURPOSE

Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs.

MATERIALS AND METHODS

In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6.

RESULTS

A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set—T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2.

CONCLUSION

The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.

Author Affiliations

¹Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; ²Clinical Pharmacology and Quantitative Pharmacology, Post Market and Lifecycle Management, AstraZeneca, Cambridge, United Kingdom; ²Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; ³Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si Gyeonggi-do, Republic of Korea; ⁴Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; ⁵Division of Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; ⁶Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea; ⁷Department of Neurosurgery, Brain Tumor Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; ⁸Department of Statistics, Keimyung University, Daegu, Republic of Korea

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