Table 2 Open in new tab Significant...

Clinical Trial Number and Reference

Number of Patients

Phase

Drug

Brain Metastases Patient Selection

Response Data

Survival Data

UMIN000001755³⁴

224

III

Prophylactic cranial irradiation vs observation in small-cell lung cancer with no brain metastases

No brain metastases at baseline

Median OS 11.6 months vs 13.7 months (HR 1.27, P = .094)

Iuchi et al.¹⁴²

Gefitinib for adenocarcinoma NSCLC with EGFR mutation

Patients with symptomatic and asymptomatic brain metastases, no radiotherapy

87.8% response rate

Median PFS 14.5 months and median OS 21.9 months.
Exon 19 deletions compared to L858R mutation were associated with better outcomes (OS P = .025)

NCT02296125⁸²

556

III

Osimertinib vs first-generation EGFR-TKI

Only patients with stable asymptomatic brain metastases included

6% of patients had CNS progression in the osimertinib group compared to 15% in the standard EGFR-TKI group

Osimertinib significantly increased PFS compared to first-generation TKIs (HR 0.46; 95% CI 0.37–0.57)

NCT01154140⁸⁷

III

Crizotinib vs pemetrexed plus cisplatin or carboplatin

Only patients with stable asymptomatic brain metastases included

Intracranial disease control rate was significantly higher with crizotinibat 12 weeks (85% vs 45%; P < .001) and 24 weeks (56% vs 25%, P = .006)

PFS was longer in crizotinib group (HR 0.40, P < .001)

NCT02075840⁹⁵

303

III

Alectinib vs crizotinib in ALK-positive NSCLC

Only patients with stable asymptomatic brain metastases included. CNS progression could receive local therapy if isolated asymptomatic CNS progression occurred

12% of patients in alectinib group had CNS progression vs 45% in crizotinib group (HR 0.16, P < .001). CNS complete response was significantly more likely in the alectinib group compared to the crizotinib group (45% vs 9%, P < .001)

PFS was longer in the alectinib group (HR 0.47, P < .001)

NCT01970865⁹⁶

276

Lorlatinib

Only patients with stable asymptomatic brain metastases included

In patients with at least one prior ALK inhibitor, 51 of 81 patients had an intracranial response (63%; 95% CI 51.5–73.4)

NCT02578680

108

III

Pemetrexed and platinum-based drug plus pembrolizumab or placebo in patients without EGFR or ALK mutations

Only patients with stable asymptomatic brain metastases included

Pembrolizumab patients had significantly longer OS (HR 0.36, 95% CI 0.20–0.62) and PFS (HR 0.42, 95% CI 0.26–0.68)

Table 2

Open in new tab

Significant Trials in Lung Cancer Brain Metastases

Clinical Trial Number and Reference	Number of Patients	Phase	Drug	Brain Metastases Patient Selection	Response Data	Survival Data
UMIN000001755³⁴	224	III	Prophylactic cranial irradiation vs observation in small-cell lung cancer with no brain metastases	No brain metastases at baseline	NA	Median OS 11.6 months vs 13.7 months (HR 1.27, P = .094)
Iuchi et al.¹⁴²	41	II	Gefitinib for adenocarcinoma NSCLC with EGFR mutation	Patients with symptomatic and asymptomatic brain metastases, no radiotherapy	87.8% response rate	Median PFS 14.5 months and median OS 21.9 months. Exon 19 deletions compared to L858R mutation were associated with better outcomes (OS P = .025)
NCT02296125⁸²	556	III	Osimertinib vs first-generation EGFR-TKI	Only patients with stable asymptomatic brain metastases included	6% of patients had CNS progression in the osimertinib group compared to 15% in the standard EGFR-TKI group	Osimertinib significantly increased PFS compared to first-generation TKIs (HR 0.46; 95% CI 0.37–0.57)
NCT01154140⁸⁷	79	III	Crizotinib vs pemetrexed plus cisplatin or carboplatin	Only patients with stable asymptomatic brain metastases included	Intracranial disease control rate was significantly higher with crizotinibat 12 weeks (85% vs 45%; P < .001) and 24 weeks (56% vs 25%, P = .006)	PFS was longer in crizotinib group (HR 0.40, P < .001)
NCT02075840⁹⁵	303	III	Alectinib vs crizotinib in ALK-positive NSCLC	Only patients with stable asymptomatic brain metastases included. CNS progression could receive local therapy if isolated asymptomatic CNS progression occurred	12% of patients in alectinib group had CNS progression vs 45% in crizotinib group (HR 0.16, P < .001). CNS complete response was significantly more likely in the alectinib group compared to the crizotinib group (45% vs 9%, P < .001)	PFS was longer in the alectinib group (HR 0.47, P < .001)
NCT01970865⁹⁶	276	II	Lorlatinib	Only patients with stable asymptomatic brain metastases included	In patients with at least one prior ALK inhibitor, 51 of 81 patients had an intracranial response (63%; 95% CI 51.5–73.4)	NA
NCT02578680	108	III	Pemetrexed and platinum-based drug plus pembrolizumab or placebo in patients without EGFR or ALK mutations	Only patients with stable asymptomatic brain metastases included	NA	Pembrolizumab patients had significantly longer OS (HR 0.36, 95% CI 0.20–0.62) and PFS (HR 0.42, 95% CI 0.26–0.68)

Clinical Trial Number and Reference	Number of Patients	Phase	Drug	Brain Metastases Patient Selection	Response Data	Survival Data
UMIN000001755³⁴	224	III	Prophylactic cranial irradiation vs observation in small-cell lung cancer with no brain metastases	No brain metastases at baseline	NA	Median OS 11.6 months vs 13.7 months (HR 1.27, P = .094)
Iuchi et al.¹⁴²	41	II	Gefitinib for adenocarcinoma NSCLC with EGFR mutation	Patients with symptomatic and asymptomatic brain metastases, no radiotherapy	87.8% response rate	Median PFS 14.5 months and median OS 21.9 months. Exon 19 deletions compared to L858R mutation were associated with better outcomes (OS P = .025)
NCT02296125⁸²	556	III	Osimertinib vs first-generation EGFR-TKI	Only patients with stable asymptomatic brain metastases included	6% of patients had CNS progression in the osimertinib group compared to 15% in the standard EGFR-TKI group	Osimertinib significantly increased PFS compared to first-generation TKIs (HR 0.46; 95% CI 0.37–0.57)
NCT01154140⁸⁷	79	III	Crizotinib vs pemetrexed plus cisplatin or carboplatin	Only patients with stable asymptomatic brain metastases included	Intracranial disease control rate was significantly higher with crizotinibat 12 weeks (85% vs 45%; P < .001) and 24 weeks (56% vs 25%, P = .006)	PFS was longer in crizotinib group (HR 0.40, P < .001)
NCT02075840⁹⁵	303	III	Alectinib vs crizotinib in ALK-positive NSCLC	Only patients with stable asymptomatic brain metastases included. CNS progression could receive local therapy if isolated asymptomatic CNS progression occurred	12% of patients in alectinib group had CNS progression vs 45% in crizotinib group (HR 0.16, P < .001). CNS complete response was significantly more likely in the alectinib group compared to the crizotinib group (45% vs 9%, P < .001)	PFS was longer in the alectinib group (HR 0.47, P < .001)
NCT01970865⁹⁶	276	II	Lorlatinib	Only patients with stable asymptomatic brain metastases included	In patients with at least one prior ALK inhibitor, 51 of 81 patients had an intracranial response (63%; 95% CI 51.5–73.4)	NA
NCT02578680	108	III	Pemetrexed and platinum-based drug plus pembrolizumab or placebo in patients without EGFR or ALK mutations	Only patients with stable asymptomatic brain metastases included	NA	Pembrolizumab patients had significantly longer OS (HR 0.36, 95% CI 0.20–0.62) and PFS (HR 0.42, 95% CI 0.26–0.68)

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