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Case Reports
. 2019 Jun 3:3:PO.19.00013.
doi: 10.1200/PO.19.00013. eCollection 2019.

Dramatic Response to Lorlatinib in a Patient With CD74-ROS1-Positive Lung Adenocarcinoma With Acquired F2004V Mutation

Anastasios Dimou  1 , Sai-Hong I Ou  2 , Robert C Doebele  1
Affiliations
Case Reports

Dramatic Response to Lorlatinib in a Patient With CD74-ROS1-Positive Lung Adenocarcinoma With Acquired F2004V Mutation

Anastasios Dimou et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Sai-Hong I. OuStock and Other Ownership Interests: Turning Point Therapeutics Honoraria: Pfizer, Roche Pharma AG, Roche, ARIAD/Takeda, AstraZeneca, Foundation Medicine, Merck Consulting or Advisory Role: Pfizer, Roche, AstraZeneca, Takeda, Foundation Medicine, Turning Point Therapeutics, Ignyta Speakers' Bureau: Genentech, AstraZeneca, Takeda Research Funding: Pfizer (Inst), Roche Pharma AG (Inst), AstraZeneca/MedImmune (Inst), AstraZeneca (Inst), ARIAD (Inst), Ignyta (Inst), Astellas Pharma (Inst), Chugai Pharma (Inst), Revolution Medicines (Inst)Robert C. DoebeleStock and Other Ownership Interests: Rain Therapeutics Consulting or Advisory Role: OncoMed, Ignyta, GreenPeptide, AstraZeneca, Roche, Bayer, Takeda, Rain Therapeutics Research Funding: Ignyta (Inst) Patents, Royalties, Other Intellectual Property: Licensing fees from Abbott Molecular for Patent PCT/US2013/057495, licensing fees from Ignyta for biologic materials (Inst), licensing fees for biologic materials from Genentech (Inst), licensing fees for patent from Rain Therapeutics Travel, Accommodations, Expenses: Ignyta, Rain Therapeutics, Roche No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Magnetic resonance images of the brain (T1 axial postcontrast series) (A) before and (B) 1 month after treatment with lorlatinib, showing significant response of all metastatic brain lesions.
FIG 2.
FIG 2.
Timeline of the clinical course, highlighting the treatment interventions and the molecular data from the time of diagnosis. cfDNA, circulating cell-free DNA; SAR, stereotactic ablative radiation.
FIG 3.
FIG 3.
Secondary mutations in ROS1 fusions reported in in vitro experiments in the literature and differential sensitivity to drugs with known ROS1 activity. The numbers in the boxes correspond to the average concentration (Cave) for the drug in steady state in patients, divided by the drug IC50 values calculated in Ba/F3 cells expressing the mutant ROS1 molecules. The half maximal inhibitory concentration (IC50) values were obtained from published reports. Colors represent relative potencies of the drugs compared with achievable drug exposure. The average IC50 was used if there was more than one publication for a certain mutation-drug combination. Repotrectinib is another potent ROS1 inhibitor with activity against many of these secondary mutations; it is not shown in the figure because the RP2D is not known yet for this drug. Cave values were calculated as the ratio of the area under the curve for 0 to 24 hours to 24 hours of the drug at steady state in patients., Secondary mutations that have been reported in clinical cases are highlighted in red and the ROS1 F2004V mutation described clinically for the first time in this report is highlighted in purple. The last column shows the homolog amino acid positions in ALK, estimated with the blastp program (https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins), and any ALK mutations at those positions reported in the literature or the Catalog of Somatic Mutations in Cancer (COSMIC) database. (*) These ALK mutations also are found in neuroblastoma.
See this image and copyright information in PMC

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