Concomitant EGFR Mutations and ALK Rearrangements in Lung Adenocarcinoma Treated With Osimertinib
David Thomas1, McKenzie E Maloney1, Girindra Raval1
1Hematology and Oncology, Medical College of Georgia, Augusta University, Augusta, USA.
Abstract:
Lung cancer is the third most common cancer in addition to being the cancer responsible for the most annual deaths in the United States, comprising 15% of all diagnosed cancers, and 28% of all cancer deaths in 2020. Major advances in survival are because of gene sequencing and the advent of targeted biological therapy. The prevalence of epidermal growth factor receptor (EGFR) mutations coexisting with anaplastic lymphoma kinase (ALK) rearrangements is quite low. However, the clinical relevance and effective treatment of these cancers require further investigation. This case series describes two patients diagnosed with stage IV adenocarcinoma with coexisting EGFR and ALK rearrangements. In Case 1, a 73-year-old male presented with worsening ataxia and headaches. In Case 2, a 64-year-old female presented with worsening dyspnea. Molecular studies revealed ALK gene fusion and the L861Q EGFR mutation in Case 1 and L858R EGFR mutation and ALK gene fusion in Case 2. Both patients received a gamma knife and an EGFR-tyrosine kinase inhibitor (TKI), osimertinib. In one of the cases, following the discovery of new brain metastases, the dose of osimertinib was increased from 80 to 160 mg. The patient passed away nine months after beginning EGFR-TKI treatment, one month after increasing the dose. The second patient experienced a significant interval reduction in the size of enhancing metastasis in both the right frontal and left parietal lobe after four months of EGFR-TKI treatment. The cases of coexisting EGFR mutations and ALK rearrangements are quite rare, and treatment can be challenging. Here, EGFR-TKI had a mixed response among our patients.
Insights
This case series explores rare instances of lung cancer with coexisting epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. Treatment with EGFR-tyrosine kinase inhibitors (TKIs) showed mixed responses in these challenging cases.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer death in the US, with survival significantly improved by targeted therapies.
- Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are key drivers in non-small cell lung cancer.
- The co-occurrence of EGFR mutations and ALK rearrangements is rare, presenting unique treatment challenges.
Observation:
- This case series details two patients with stage IV lung adenocarcinoma harboring both EGFR mutations and ALK rearrangements.
- Patient 1, a 73-year-old male, presented with neurological symptoms; Patient 2, a 64-year-old female, experienced dyspnea.
- Molecular analysis confirmed ALK gene fusion with an EGFR L861Q mutation in Patient 1 and an EGFR L858R mutation with ALK gene fusion in Patient 2.
Findings:
- Both patients received stereotactic radiosurgery (gamma knife) and an EGFR-tyrosine kinase inhibitor (TKI), osimertinib.
- One patient experienced disease progression with new brain metastases, requiring an increased osimertinib dose, and ultimately passed away nine months after treatment initiation.
- The second patient demonstrated a significant reduction in brain metastasis size after four months of osimertinib treatment.
Implications:
- The management of lung cancer with concurrent EGFR mutations and ALK rearrangements is complex due to their rarity.
- EGFR-TKIs can be effective, but treatment outcomes are variable, necessitating further research into optimal therapeutic strategies.
- This case series highlights the need for comprehensive molecular profiling to guide personalized treatment approaches in lung cancer.
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