From the Guidelines
The first-line treatment for ROS1-positive non-small cell lung cancer (NSCLC) is typically crizotinib (Xalkori), administered at 250 mg twice daily, due to its high response rate of about 70%–80% and median duration of response of 19.7 months, as shown in a phase II single-arm trial 1. The treatment options for ROS1-positive NSCLC include:
- Crizotinib (Xalkori) at 250 mg twice daily
- Entrectinib (Rozlytrek) at 600 mg once daily
- Ceritinib (Zykadia) at 450 mg once daily with food
- Lorlatinib (Lorbrena) at 100 mg once daily
- Repotrectinib, a next-generation ROS1, TRK, and ALK TKI, which has shown a confirmed objective response of 79% among those who had not received a ROS1 TKI and 38% among those who had received one ROS1 TKI 1 These medications are taken orally and continued until disease progression or unacceptable toxicity occurs. Common side effects include:
- Vision disturbances
- Nausea
- Diarrhea
- Liver enzyme elevations
- Edema Regular monitoring with liver function tests, electrocardiograms, and vision assessments is necessary, as shown in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer, Version 4.2024 1. These drugs work by blocking the abnormal ROS1 protein that drives cancer growth, effectively targeting the specific molecular alteration rather than attacking all rapidly dividing cells like traditional chemotherapy. ROS1 testing is essential before starting treatment to confirm the presence of the gene rearrangement, as these medications are only effective in patients with this specific genetic alteration, as recommended in the pan-asian adapted clinical practice guidelines for the management of patients with metastatic non-small-cell lung cancer 1.
From the FDA Drug Label
ROZLYTREK is indicated for the treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC), as detected by an FDA-approved test. The Entrectinib (PO) drug, also known as ROZLYTREK, is used to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC) in adults, as detected by an FDA-approved test 2.
- The drug is specifically indicated for patients with ROS1-positive NSCLC.
- ROS1 positivity should be detected by an FDA-approved test.
- The treatment is for adult patients with metastatic NSCLC.
From the Research
Ros 1 Drug Overview
- Ros 1 drug, also known as crizotinib, is a tyrosine kinase inhibitor used to treat non-small cell lung cancer (NSCLC) with ROS1 gene rearrangements 3, 4, 5, 6, 7.
- Crizotinib has shown significant activity in ROS1-rearranged lung cancer and is considered the gold standard first-line treatment 4, 5.
Efficacy of Crizotinib
- Crizotinib has demonstrated a significantly longer median progression-free survival (PFS) compared to platinum-based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants 3.
- The median PFS with first-line crizotinib treatment was significantly longer in patients harboring CD74 fusion variants compared to those harboring non-CD74 fusion variants 3.
- Crizotinib has shown an objective response rate (ORR) of 66% in patients with ROS1-positive mNSCLC, with a median duration of response of 18.3 months 5.
Resistance Mechanisms and Newer Generation Therapies
- Despite the initial response to crizotinib, most patients develop disease progression, which may be intracranial or extracranial 6, 7.
- Newer generation tyrosine kinase inhibitors with increased potency against ROS1 and ROS1-resistance mutations, and improved intracranial activity are under evaluation in clinical trials 4, 6, 7.
- Sequential treatment with crizotinib followed by lorlatinib has been associated with improved overall survival (OS) in patients with ROS1-rearranged NSCLC 6.
Treatment Patterns and Clinical Outcomes
- Treatment patterns and clinical outcomes among patients with ROS1-rearranged NSCLC progressing on crizotinib have been studied, and results show that a subset of patients may benefit from treatment with TKIs beyond progression 6.
- Patients treated with sequential ROS1 TKIs had a significantly longer median OS compared to those who were not 6.