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 in treatment.
- 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.
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 also have a high rate of 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