Case of an NTRK Fusion-Positive Lung Cancer Patient

Luis Raez, MD: We’re discussing today a 67-year-old patient who was newly diagnosed with adenocarcinoma of the lung. This patient presented with a 2.7-cm mass in the right lobe, and this was discovered on a chest x-ray [radiograph]. This was corroborated later by a CT [computed tomography] scan, and a CT-guided biopsy proved that this is an adenocarcinoma. Nowadays, for all patients with lung cancer, it’s necessary to perform genomic profiling of their tissue or blood. In this case, the genomic profiling of this patient that was done in his tissue showed that he does not carry the most common mutations, such as EGFR, ALK, ROS1, or BRAF. However, it was very interesting to find that this patient caries an NTRK fusion or translocation.

As part of the work-up, the patient had an MRI [magnetic resonance imaging] scan of the brain, and it showed that he already has a single, small metastatic lesion measuring less than 1 cm. With this picture—a patient with metastatic adenocarcinoma of the lung and an NTRK-fusion protein—it was decided to treat him with larotrectinib. Larotrectinib is a new tyrosine kinase inhibitor that we’re going to review for these type of genetic alterations.

It was very interesting to observe the decision to not administer stereotactic brain radiation therapy to the single metastatic lesion. That has been our standard of care for many years, but now we have an agent that can penetrate the central nervous system. Maybe these patients will no longer need to be treated with stereotactic brain radiation, at least not at the beginning of therapy. This patient was treated successfully with larotrectinib. The standard dosage is 100 mg twice a day, and he responded for several months and has stayed in remission for a long time. That’s why we found this case to be very interesting.

When we talk about incidence of NTRK fusions, we know they’re common in lung cancer. It’s a very interesting topic. I remember I had the honor of presenting data at the IASLC [International Association for the Study of Lung Cancer] World Conference on Lung Cancer 3 years ago in Denver, Colorado. At that time, the few data that were available showed that around 5% of lung cancers had these genetic alterations because each alteration occurred around 1.5% of the time, and when you added the 3 genes together, we would have close to 5% incidence. However—as it happens in most types of science—as we performed more testing, we found that the incidence is very low. For example, in the paper that we published with the first 55 patients in the New England Journal of Medicine, we found that the incidence was around 1% for all solid tumors.

Nowadays, in lung cancer, we have hundreds of thousands of patients tested, and we know that around 0.3% of patients have NTRK fusions. In my own experience at my institution, the first time we tested for NTRK fusions in around 400 patients with lung cancer, we found only 3 among 400. That’s why the incidence is very low. However, it’s very meaningful because there are around 225,000 new patients with lung cancer every year in the United States. Even 0.3% is a large number of patients and more common than some other rare cancers. That’s why I think it’s very worth testing everybody, because we need to identify these thousands of patients who are going to benefit from this type of genetic alteration.

Transcript edited for clarity.

Case: A 67-Year-Old Man With NTRK Fusion-Positive Metastatic Non-Small Cell Lung Cancer

Initial presentation

A 67-year old man presented with a 2-month history of cough and dyspnea on exertion

PMH/SH: hypercholesterolemia, never smoker

PE: right-sided wheezing on auscultation

Clinical workup

Labs: WNL

Chest X-ray showed a right-side mass ~2.5 cm

Chest/abdomen/pelvic CT showed a 2.7-cm solid pulmonary lesion in the right lobe, ipsilateral mediastinal lymph node involvement

CT‐guided core needle biopsy of the lung lesion and lymph node revealed lung adenocarcinoma, grade 3

Contrast‐enhanced MRI of the head showed a small lesion (0.6 cm); indicating CNS metastasis

Molecular and genomic testing:NTRK+, BRAF-, EGFR-, ALK-, ROS1-,KRAS-, PD-L1 0%

Stage T1cN2M1b; ECOG PS 1

Treatment and Follow-Up

Larotrectinib 100 mg PO BID was initiated; treatment was well-tolerated

Stereotactic radiosurgery of the brain was deferred due to location and increased risk of post-operative morbidity

Imaging at 2 months showed stable disease; sustained response upon follow-up

Imaging at 18 months showed decreased size of pulmonary and brain lesions

Repeat genomic testing: NTRK+