346P - The safety and efficacy of intrathecal chemotherapy with pemetrexed via the Ommaya reservoir for leptomeningeal metastases from lung adenocarcinoma: A prospective study

Background

In this prospective clinical study, we aimed to evaluate the efficacy and toxicities of intrathecal chemotherapy (IC) with pemetrexed via the Ommaya reservoir in lung adenocarcinoma (LUAD) with refractory leptomeningeal metastases (LM).

Methods

LUAD-LM patients who had failed at least two prior treatments were recruited. After the implantation of the Ommaya reservoir, 30 mg to 50 mg pemetrexed was administered on Days 1 and 8 every 3 weeks via the Ommaya reservoir. Serial samples of cerebrospinal fluid (CSF) and plasma were obtained for pharmacokinetic studies. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and therapeutic toxicities.

Results

Twenty-six patients were enrolled and analyzed. Clinical outcomes included response in 10 patients, stable disease in 9 patients and disease progression in 4 patients, revealing an ORR of 43.5% and DCR of 82.6%. The median PFS and OS were 6.3 and 9.2 months, respectively. Three patients without imaging evaluation or CSF cytology after treatment were not evaluable. Grade 1-2 myelosuppression (9/26, 34.6%), elevation of transaminase (6/26, 23.1%) and anaemia (4/26, 15.4%) were the three main adverse events. Dose-limiting toxicity was only observed in two patients (2/26, 7.7%), and 30 mg pemetrexed was considered as the recommended dose for IC. Pharmacokinetic analysis showed that using Ommaya reservoirs, higher pemetrexed concentrations and prolonged half-lives were achieved in the CSF compared with lumbar puncture (LP).

Conclusions

Intrathecal pemetrexed at a dose of 30 mg via the Ommaya reservoirs on Days 1 and 8 every 21 days achieved promising disease control and satisfactory survival with moderate toxicities in resistant LUAD-LM. Ommaya reservoirs may be a more convenient and safer route to implement IC, especially for the patients who cannot tolerate LP.

Clinical trial identification

ChiCTR2000028936.

Editorial acknowledgement

Legal entity responsible for the study

Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School.

Funding

Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School.

Disclosure

All authors have declared no conflicts of interest.