Combined Lorlatinib, Dabrafenib, and Trametinib Treatment for ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer with a Lorlatinib-Induced BRAF V600E Mutation: A Case Report

Figures & data

Figure 1 Diagram of patient’s treatment history and clinical course. (A) Timeline of treatment; (B) Change of tumor lesions upon the combined treatment with dabrafenib, trametinib and lorlatinib. The arrow denotes pericardial or pleural effusion; Two months after the treatment beginning, both pericardial and effusions declined; lung lesion remained stable; Three months after the treatment beginning, the arrow denotes the increased pleural effusion, lung lesion remained stable.

Abbreviations: ARMS-PCR, amplification refractory mutation system PCR; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; NGS, next-generation sequencing; AP, pemetrexed + cisplatin; PR, partial response; SD, stable disease; PFS, progression-free survival; TTF, time to treatment failure.

Table 1 List of Alterations Detected by NGS

Sample Collection Time	PD on 1st Line (Dec. 2019)	PD on 2nd Line (Mar. 2021)	PD on 3rd Line (Nov. 2021)	4th Line SD (Mar. 2022)
Sample type	Plasma	Plasma	Pericardial effusion	Pleural effusion
Alterations/Features	Allele frequency
MED13L-ROS1 (M1:R34)	20.51%	4.08%	40.85%	48.46%
EZR-ROS1 (E11:R34)	4.19%	1.23%	14.64%	15.29%
ARID1A c.1921-2A>T	0.69%	/	48.23%	51.58%
NF1 p.G127Ter	/	1.26%	/	/
BRAF p.V600E	/	/	37.27%	29.12%
NFE2L2 p.T80A	/	/	22.40%	34.03%
FGF19 amp	/	/	CN:3.4	/
FGF4 amp	/	/	CN:3.7	/
FGF3 amp	/	/	CN:3.7	/
NRAS p.Q61R	/	/	/	9.16%
NTRK amp	/	/	/	CN:4.2
CDKN2A del	/	/	/	CN:0.9

Figure 2 IGV illustration of ROS1 novel fusion and potential drug-resistant mutations. (A) MED13L-ROS1(M1:R34); (B) NF1 p.G127Ter; (C) BRAF, c.1799T > A, p.V600E; (D) NRAS, c.182A>G, p.Q61R.