Treatment in NTRK Fusion-Positive Lung Cancer


Luis Raez, MD: Usually, when we find a genetic alteration that can be targeted, that is the preferred modality for treatment. In this case, I don’t have any doubt that this patient may benefit from chemotherapy or a combination of chemotherapy and immunotherapy. However, if we can have this patient on a nontoxic targeted agent for 1 or 2 years with outstanding quality of life, that would be our preferred approach. We have 2 agents approved by the FDA for NTRK fusions, and these are larotrectinib and entrectinib. Both of these agents are already in the market and approved for treatment of this genetic alteration.

Historically speaking, we have been using larotrectinib in most of these patients because, first of all, many of us have more experience with larotrectinib. Some of us were part of the group that originally studied this agent. Larotrectinib was approved first. For that reason, I think there is, in America, more experience with the use of larotrectinib. This patient was treated, responded very well, and was able to remain in remission for several months. Normally, we take these patients and perform evaluations like CT [computed tomography] scans or PET [positron emission tomography] scans every 2 to 3 months to be sure that the patients are stable or are not progressing. If we see signs of progression, such as a new tumor or an increase in the size of the tumors greater than 20%, we call that a failure, and then we have to switch to another agent. But in this case, treatment was successful because of these reasons.

This case is very important because of the brain metastases. As we mentioned before, the standard of care in America is to use stereotactic brain radiation every time we have new metastases. As long as we have fewer than 3 or 4 brain metastases—and the number keeps changing—we use stereotactic brain radiation. We have been doing this successfully for more than 10 years. But thanks to targeted agents such as larotrectinib or entrectinib that have brain penetration, the patient in the case that we presented had a response in the central nervous system. The patient didn’t have to receive radiation to the brain. That’s a major advance because radiation to the brain, even if this is stereotactic—a limited amount of radiation—can generate brain necrosis or other consequences in the years to come.

Nowadays, our patients with lung cancer live for several years, so we’re seeing brain necrosis and other adverse effects of this treatment. That is why with agents like larotrectinib or entrectinib—if there are 1, 2, or 3 small brain metastases—our standard of care has changed recently. Now we prefer oral therapy and do an assessment of the brain, and most of the time we see that if there are brain responses, we don’t have to use radiation therapy at the beginning of treatment.

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+

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