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Thorac Cancer
2022 Feb 01;134:637-642. doi: 10.1111/1759-7714.14291.
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Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent EGFR mutations and DCTN1-ALK fusion.
Yin Q
,
Guo T
,
Zhou Y
,
Sun L
,
Meng M
,
Ma L
,
Wang X
.
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The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. The co-occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1-ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions after she acquired osimertinib resistance. Furthermore, we summarize 22 published cases of patients with lung adenocarcinoma with concurrent EGFR mutation and ALK rearrangement, including details of clinical characteristics, natural history, and pertinent therapy of this uncommon tumor subtype. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co-alterations in the pre-alectinib era and that ALK inhibition with crizotinib did not show more eye-catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.
FIGURE 1. The patient's treatment history and chronological imaging follow‐up results. (a) Chest CT, brain MRI, and chest X‐ray images of the patient before and after treatment. The red arrow in the chest CT of August 2018 indicates new metastases in the lung; the red arrows in the chest x‐rays of April 2020, June 2020, and January 2021 indicate the pleural fluid line. (b) Timeline of multiline treatment and summary of the duration of each treatment
FIGURE 2. Detection of dynactin subunit 1 (DCTN1) and the anaplastic lymphoma kinase fusion (DCTN1‐ALK). (a) Detailed fusion site of DCTN1‐ALK. (b) NGS results showed a breakpoint of fusion. (c) The DCTN1‐ALK fusion was further confirmed by FISH and immunohistochemistry of the primary lung tumor tissue. (Left) A split signal was observed in 68% of cells. (Right) Immunohistochemistry indicated strong ALK expression
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