Management of Toxicities of Larotrectinib

Luis Raez, MD: The management of these toxicities is not very complicated because the toxicities are what is commonly seen. For example, with larotrectinib, some patients have anemia, but the management of anemia is very easy. We don’t do anything until the hemoglobin goes down to around 7g/dL, and sometimes we transfuse patients. Weight gain is something that doesn’t matter to our patients because some of our patients are malnourished and underweight. We monitor the liver function tests, certainly, and we will dose reduce if we see toxicity.

We monitor the leukocyte count, the white blood cell count, and the ANC, or absolute neutrophil count. There has been a very low incidence of leucopenia or neutropenia, and certainly we will use a dose adjustment if that’s the case with these agents. Something peculiar with these agents is the dizziness. Patients feel a little dizzy. But most of the patients say that does not affect their daily activities, that it’s something that can be tolerated until we can find a better way to administer these agents.

What is important to know about duration of response is that it provides extra time to the patient and prolongs their survival, because we are delaying the onset of palliative chemotherapy that has a well-known outcome. Duration of response opens the possibility of hope. For example, this patient in the case that we are discussing today has been on larotrectinib for 18 months. You already have 18 months of extra life. However, during these 18 months, there is another agent, LOXO-195, that has been developed to overcome resistance. Now this patient doesn’t have to be on chemotherapy. When he started the clinical trial, maybe the only option was larotrectinib and then chemotherapy; whereas nowadays, the patient has a second option because there has been a durable response. That’s the benefit. Nowadays, we are developing drugs very quickly. Even a durable response and stable disease is worth it because we can find something when the patients progress, and we don’t have to put them on chemotherapy right away.

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+