case
- A 59-year-old woman presented to her primary care physician complaining of non-cough, chest pain, and intermittent low back pain that had persisted for 6 weeks.
- The patient was a lifelong nonsmoker and had no history of cardiovascular disease, peripheral vascular disease, or diabetes.
- There was no family history of malignancy.
- Hypertension is well controlled with angiotensin II receptor antagonist 160 mg orally once daily.
- Blood pressure, 114/76 mmHg.pulse, 78 bpm, regular
- ECOG performance status: 0
- Pulmonary report: Decreased breath sounds on auscultation over the posterior right midline.
- Chest radiograph: An opaque mass is visible in the center of the right lung field.
- Patient referred to thoracic oncologist for further consultation and evaluation
- Chest CT: Visualized solid, 7 cm, centrally concentrated right middle lobe mass. No evidence of bronchography, cavitation, or calcification.Ipsilateral positive, 20 mm, mediastinal lymph node
- Fludeoxyglucose F18 PET/CT: Active uptake from L3 to L5 was detected.bilateral iliac crests and ischial spines
- Brain MRI: negative for suspicious lesions
- The patient underwent endobronchial ultrasound-guided transbronchial needle aspiration without complications.
- Immunohistochemistry of formalin-fixed paraffin-embedded tissue specimens was positive for elevation. ROS1 Microgranular cytoplasmic protein levels (H-score > 150). TTF-1 positive. PD-L1: (<1%)
- histopathology: Adenocarcinoma characterized by aggregation of malignant glandular cells. Enlarged pleomorphic nucleus. Vesicular nuclear chromatin. and high nuclear-to-cytoplasmic ratio.
- Molecular profiling: positive ROS1 (including CD74 gene partner); negative for other actionable mutations.
- Stage: T3N2M1b
First-line treatment
- Pre-treatment liver function tests: Serum alanine transaminase, aspartate transaminase, and bilirubin concentrations are within normal limits.
- The patient began a course of repotrectinib (Augtyro) 160 mg orally once daily for 14 days, then increased to 160 mg orally twice daily until disease progression or unacceptable toxicity. To do.
- The patient experienced intermittent, mild, self-limiting episodes of dizziness that did not require interruption or delay of dosing.
- On day 14 of lepotrectinib administration, it was recommended to increase the total daily dose to 320 mg.
follow up plan:
- Return to the office every three months.
- Monitor treatment response for sustained efficacy and tolerability.
- Repeat diagnostic tests, including imaging tests, as needed.
targeted oncology: Why do non-small cell lung cancer (NSCLC) patients receiving lepotrectinib experience dizziness during treatment?
Vamsidhar Velcheti, MD, MBA: [After this patient starts repotrectinib], during the first 2 weeks of treatment, intermittent dizziness, which is common with lepotrectinib, occurred. These drugs include [a lot of] There are interactions, and repotrectinib is also a TRK inhibitor. [toxicity] The problem arises from.1 These patients experience dizziness when they first stop these drugs. [they could even experience] Ataxia, which is usually caused by initial TRK activity. That’s something to remember.
Vamsidhar Velcheti, MD, MBA
Professor of Medicine
New York University Grossman School of Medicine
Thoracic Oncology Program Director
New York University Langone Health
Perlmutter Cancer Center
New York, New York
What were the patient characteristics in the Phase 1/2 TRIDENT-1 trial (NCT03093116)?
[In the phase 1/2 TRIDENT-1 trial]they established a phase 1 dose escalation of 160 mg [of repotrectinib] After 2 weeks, increase to 160 mg twice daily.2 [Patients on the phase 2 dose escalation were split into cohorts based on] If they were ROS1 tyrosine kinase inhibitors, [TKI] There were 1 case of TKI with chemotherapy, 2 cases of TKI without chemotherapy, and 1 case of TKI without chemotherapy.
Primary endpoints include objective response rate. [with secondary end points of duration of response and time to response]. Most of the patients who were not smokers had no history of smoking. ROS1 TKI treatment in a high proportion of patients.It is generalized that non-smokers are female patients. [and in this study they made up most patients in both the no prior TKI (61%) and 1 prior TKI with no chemotherapy (68%) cohorts].2 I think you need to consider the probability of pre-testing. [the patient] They are also more likely to carry oncogenic mutations.
What is the efficacy data behind the use of repotrectinib in the NSCLC population?
approval [for repotrectinib] It was…accelerated approval. 3 majority [of the patients in this study] The patient responded to lepotrectinib and showed progression-free survival. [patients with no prior ROS1 TKI therapy] It was almost 3 years, [at a median of 35.7 months (95% CI, 27.4–not estimated [NE])].2
This was notable and led to a boost [at looking at phase 3 data for this patient population on repotrectinib]. Even if the patient was previously treated with a ROS1 TKI…[had a nice ORR of 38% (95% CI, 25%-52%)]….We saw tumor shrinkage in every patient in that cohort of trials…and these are the profound responses we’re seeing. [with repotrectinib in both the TKI naïve and 1 prior TKI cohort with a median DOR of 34.1 months (95% CI, 25.6%-NE) and 14.8 months (95% CI, 7.6%-NE), respectively].2
References:
1. Han SY. TRK inhibitors: tissue-independent anticancer agents. Pharmaceuticals (Basel). 2021;14(7):632. doi:10.3390/ph14070632
2. Drilon A, Camidge R, Lin J, et al. Repotrectinib for ROS1 fusion-positive non-small cell lung cancer. N English J Medicine. 2024; 390:118-131. doi: 10.1056/NEJMoa2302299
3. FDA approves repotrectinib for ROS1-positive non-small cell lung cancer. news release. F.D.A. November 16, 2023. Accessed February 20, 2024. http://tinyurl.com/4hd9n7sc
