Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan

Figures & data

Figure 1. Multifocal brain metastasis response to T-DXd.

Side-by-side comparison of post contrast, T1-weighted MRIs done before (left-sided panels) and 6 weeks after initiation of T-DXd. Each arrow indicates a metastasis that resolved after treatment initiation.

TDXd: Trastuzumab deruxtecan.

Table 1. Metastasis evolution after 2 months of initial (1A) and subsequent (1B) T-DXd administration.

Table 1A. Metastasis evolution after 2 months of initial T-Dxd administration.
Lesion	Maximal diameter (mm)		% change	Measurable (>5 mm)	RANO-BM response
	Baseline	After T-Dxd (2 mo)
1	38	41.1	8.2	^†	^†
2	6.5	0	‐100.0	X	CR
3	2.4	0	‐100.0
4	9.5	0	‐100.0	X	CR
5	14.7	0	‐100.0	X	CR
6	8.5	8.4	‐1	^† ^, ^‡	^† ^, ^‡
7	7.6	0	‐100.0	X	CR
8	8.6	9.4	9.3	^† ^, ^‡	^† ^, ^‡
9	8.6	0	‐100.0	X	CR
10	1.8	0	‐100.0
11	9.6	0	‐100.0	X	CR
12	3.0	0	‐100.0
13	14.7	0	‐100.0	X	CR
14	8.1	0	‐100.0	X	CR
15	6.9	0	‐100.0	X	CR
16	2.5	0	‐100.0
Table 1B. Metastasis evolution after 2 months of rescue T-Dxd administration.
Lesion	Maximal diameter (mm)		% change	Measurable (>5 mm)	RANO-BM response
	Before T-Dxd	After T-Dxd (2 mo)
1	33.8	30.5	‐9.8	^†	^†
2	12.7	10.3	‐18.9	X ^§	SD
3	8.7	6.4	‐26.4	X	SD
4	29.1	27.2	‐6.5	^†	^†
5	10.3	6.2	‐39.8	X ^§	PR
6	9.2	8.2	‐10.9	X ^§	SD
7	4.7	1.0	‐78.7
8	7.7	8.2	6.5	X	SD
9	9.9	0	‐100.0	X ^§	CR
10	4.3	2	‐53.5
11	3.8	0	‐100.0
12	9.1	0	‐100.0	X ^§	CR

† Biopsy-proven to represent treatment effect and not recurrent metastatic disease.

‡ These two lesions subsequently enlarged and became confluent. Lesion 4 in Table 1B represents the confluence of lesions 6 & 8 in Table 1A. The remainder of lesions listed in Table 1B do not necessarily correspond to those in Table 1A.

§ Target lesions (those with the five largest diameters) for the purposes of intracranial response assessment.

CR: Complete response; mo: months; PR: Partial response; RANO-BM: Response Assessment in Neuro-Oncology Brain Metastases; SD: Stable disease; TDXd: Trastuzumab deruxtecan.

Figure 2. Severe necrosis of two metastases.

(A) T1-weighted, post contrast MRI showing prominent size of a dominant left frontoparietal lesion. (B) Postoperative pathology showing necrotic and fibrinous material and, at upper right, dystrophic mineralization without evidence of active tumor (H&E staining). (C) T1-weighted, post contrast MRI showing a dominant, bilobed left frontal lesion with surrounding vasogenic edema responsible for the patient’s symptoms and treated via LITT. (D) Pathology of the targeted lesion showing tissue necrosis with few mononuclear cells (H&E).

LITT: Laser-interstitial thermal therapy.

Figure 3. Multifocal brain metastasis response to T-DXd with rechallenge.

Post contrast T1-weighted MRI showing (A) progression of CNS disease in the setting of a T-DXd holiday and (B) improvement of most lesion upon T-DXd reinstatement (2 months after (A)). Each arrow indicates a metastasis that resolved after treatment initiation.

TDXd: Trastuzumab deruxtecan.