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Consult

Clinician-to-Clinician Update

Masonic Cancer Clinic
Clinics and Surgery Center
909 Fulton St., SE, Suite 202
Minneapolis, MN 55455

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Diagnostics and Targeted Lung-Cancer Therapy Provide Positive Outcomes

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A 66-year-old woman who had never smoked was seen at a community facility after she experienced neck pain and 2 months of left upper-extremity numbness and weakness. She was initially managed conservatively with physical therapy and pain medications. Later, an MRI scan of her cervical and thoracic spine revealed severe degenerative cervical stenosis and lytic lesions at C2 and the spinous process of T1 vertebrae. 

Diagnosis and Management

Biopsy of the lesion at T1 revealed adenocarcinoma, consistent with primary lung carcinoma. Subsequent PET/CT scanning showed a 2 x 2 cm mass in the left upper lobe of the lung and hilar and mediastinal adenopathy with hypermetabolic activity, several bony lesions, including at the left 8th rib, and metastasis to the skull. At this point, she was referred to University of Minnesota Health Cancer Care physicians for further management. The patient had not undergone molecular testing, and physicians discussed initiating treatment versus waiting for results of molecular diagnostics. The care team decided to schedule chemotherapy 2 weeks from the initial visit with the understanding that if molecular studies revealed a mutation, physicians would cancel chemotherapy and instead use targeted therapy.

Diagnostics revealed that the patient had a PDL-1 expression level <1% with a low tumor mutation burden (2 mutations/megabase pair). Mutational analysis revealed an EGFR exon 19 deletion. Her chemotherapy appointments were cancelled, and she was started on 150 mg erlotinib daily. She experienced a fairly severe rash on this dose and had her regimen reduced to 100 mg daily after 2 weeks. Two months after initiating treatment, she experienced a dramatic reduction in the tumor burden in her lung and spine, and the patient reported reduced pain and improved quality of life. She has remained on this treatment for 9 months and is continuing to respond to therapy.

Discussion

This case highlights the importance of obtaining molecular diagnostic information to guide treatment decision-making. During her initial treatment prior to referral, this patient did not get the appropriate molecular diagnostics immediately, and without that information, she may have received suboptimal therapy. Our treatment protocol is for all patients who have lung adenocarcinoma to undergo reflexive testing for targetable EGFR, BRAF, ERBB2, and MET mutations as well as ALK and ROS1 gene rearrangements. In this case, the testing led to a choice of targeted therapy rather than chemotherapy.

Although these mutations are only seen in about 20% of patients with lung cancer, identifying them early is important so that patients are able to receive the safest and most effective treatment. In addition to these mutations, we believe that up to 50% of patients with lung cancer will have an identifiable mutation that can be treated effectively with a targeted therapy. One example is the recent finding that tyrosine receptor kinase (TRK) mutations can be targeted with entrectinib, currently being tested in a clinical trial at the University of Minnesota. Should this therapy prove effective in TRK-mutated cancers, TRK-mutation testing could become part of standard reflexive testing. Ultimately, the goal is to have effective therapies for the vast majority of patients with newly diagnosed lung cancer. 

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