Table 1. Response to multikinase inhibition in RET-rearranged lung cancers.

The best objective response and the best intracranial response to multikinase inhibitor therapy (single agent or combination therapy) with activity against RET were determined by RECIST v1.1.

Drug	Fusion	Line of TKI Therapy	Measurable Intracranial Disease at Baseline	Evaluable Intracranial Disease at Baseline	Active Untreated Intracranial Disease Pre- TKI	Best Intracranial Response	Best Overall Response*	Duration of Therapy (months)	TKI Response Rate1
Alectinib									1/2 (50%)
Case 1	CCDC6-RET	2nd	Yes	Yes	Yes	PR	PR	9.0
Case 2	KIF5B-RET	1st	Yes	Yes	Yes	SD	PD	1.8
Cabozantinib									0/3 (0%)
Case 3	KIF5B-RET	1st	Yes	Yes	Yes	SD	SD	7.4
Case 4	FISH+	1st	Yes	Yes	Yes	SD	SD	1.6
Case 5	RUFY2-RET	1st	Yes	Yes	Yes	PD	PD	0.9
Case 6	KIF5B-RET	1st	No	Yes	Yes	SD2	SD	23.6
Case 7	FISH+	1st	No	Yes	Yes	SD2	SD	40.8
Case 8	FISH+	1st	No	Yes	Yes	PD2	PD	1.6
Ponatinib									0/3 (0%)
Case 1	CCDC6-RET	1st	Yes	Yes	Yes	PD	SD	5.0
Case 9	KIF5B-RET	2nd	Yes	Yes	Yes	SD	PD	3.0
Case 10	KIF5B-RET	1st	Yes	Yes	Yes	PD	PD	0.9
Case 11	KIF5B-RET	1st	No	Yes	Yes	SD2	SD	4.0
Sunitinib									N/A
Case 9	KIF5B-RET	1st	No	Yes	No (prior RT)	PD3	SD	4.4
Vandetanib									0/1 (0%)
Case 9	KIF5B-RET	3rd	Yes	Yes	Yes	SD	SD	4.7+
Vandetanib + Everolimus									1/2 (50%)
Case 12	CCDC6-RET	3rd	Yes	Yes	Yes	PR	SD	6.8
Case 1	CCDC6-RET	3rd	Yes	Yes	Yes	SD	SD	3.7
Case 13	KIF5B-RET	2nd	No	Yes	Yes	SD3	SD	2.5

^1–overall response rate only in patients with measurable disease at baseline,

^2–intracranial response in non-target lesions,

^3–brain radiation (RT) administered prior to sunitinib, but first follow-up brain scan revealed progression of disease on sunitinib; TKI – tyrosine kinase inhibitor, FISH+ – positive RET fluorescence in situ break apart test;

⁺(under duration of therapy) – indicates that therapy is ongoing; PR – partial response. SD – stable disease. PD – progression of disease. N/A – not applicable.

^*–refers to the best overall response (extracranial and intracranial)