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Page 14 of 20 Pellerino et al. J Cancer Metastasis Treat 2020;6:41 I http://dx.doi.org/10.20517/2394-4722.2020.80

Table 6. Ongoing clinical trials on LM from NSCLC
Study No. of patients Treatment Outcomes
2
NCT04356118 30 Recombinant human endostatin 7.5 mg/m / Primary:
Phase 4 day once a day for 2 weeks and 1 week off OS
plus intrathecal MTX plus targeted therapy Neurological PFS
(EGFR TKIs or ALK inhibitors) Adverse events
Secondary:
ORR
NCT04343573 100 Arm 1: proton CSI (30 Gy/30 fr) plus Primary:
Phase 2 standard of care for LM per physician choice CNS PFS
Arm 2: proton CSI (30 Gy/10 fr) alone Secondary:
OS
NCT04356222 30 Durvalumab 10 mg/kg every 2 weeks plus Primary:
Phase 4 intrathecal MTX OS
Neurological PFS
Adverse events
Secondary:
ORR
NCT04192981 36 WBRT (30 Gy/10 fr) plus GDC-0084 in 3+3 Primary:
Phase 1 dose-escalation cohort: 45, 60, 75 mg daily, MTD
with a potential dose de-escalation cohort to Secondary:
30 mg Local recurrence rate
NCT04425681 20 Osimertinib 80 mg daily plus bevacizumab Primary:
Phase 2 7.5 mg/kg every 3 weeks PFS
ORR
Secondary:
Adverse events
NCT04148898 80 Arm 1: Osimertinib 80 mg daily alone Primary:
Phase 2 Arm 2: Osimertinib 80 mg daily plus PFS
bevacizumab 7.5 mg/kg every 3 weeks ORR
Secondary:
OS
Adverse events
NCT03719768 23 Avelumab 800 mg iv every 2 weeks plus Primary:
Phase 1b WBRT (30 Gr/10 fr) Safety and dose limiting toxicity
Secondary:
ORR
Number of T cells in CSF
Activation status of T cells in CSF
NCT03091478 13 Pembrolizumab 200 mg every 3 weeks Primary:
Phase 2 ORR

MTX: methotrexate; EGFR TKIs: epidermal growth factor receptor tyrosine kinase inhibitors; ALK: anaplastic lymphoma kinase; OS: overall
survival; PFS: progression-free survival; ORR: objective response rate; CSI: craniospinal irradiation; WBRT: whole-brain radiotherapy;
MTD: maximum tolerated dose; LM: leptomeningeal metastases; NSCLC: non-small-cell lung cancer

a diffuse linear enhancement LM has been correlated with a prolonged OS compared with nodular LM
from NSCLC [4,57] . Those 2 models may not be reliable to predict the prognosis of LM from NSCLC without
an integration of molecular markers, especially in patients with druggable mutations. Some authors have
suggested a prognostic assessment integrated with molecular alterations (molGPA) to predict the outcome
of LM patients from NSCLC. In particular, 301 patients with LM from NSCLC were scored using the
molGPA and classified them into 3 prognostic groups of high, intermediate and low risk (molGPA score of
0, 0.5-1.0 and 1.5-2.0, respectively). The median OS of high, intermediate and low risk LM patients were 0.3,
3.5 and 15.9 months, respectively (P < 0.001). Moreover, EGFR/ALK positivity, KPS ≥ 60, and absence of
extracranial metastases are independent predictive factors for better OS .
[143]

CONCLUSION
The leptomeningeal space remains a sanctuary site, with limited penetration of drugs. Recent advances
in diagnosis and treatment have been made, but several issues are still unaddressed. A standardized MRI
assessment for evaluating LM at diagnosis and during follow needs to be validated in prospective cohorts.
Similarly, CSF liquid biopsy could be a useful tool for diagnosis and monitoring of LM, especially in those