Xalkori (crizotinib) vs Augtyro (repotrectinib)

Xalkori (crizotinib) and Augtyro (repotrectinib) are both targeted therapies used to treat certain types of cancer, but they differ in their specific indications and mechanisms of action. Xalkori is approved for the treatment of non-small cell lung cancer (NSCLC) with specific genetic alterations (ALK or ROS1), and it works by inhibiting these cancer-driving proteins. Augtyro, on the other hand, is designed to target a broader range of mutations, including those resistant to earlier treatments, and is used for the treatment of solid tumors with NTRK gene fusions, ROS1 or ALK mutations, providing an option for patients who might have developed resistance to prior therapies such as Xalkori. When deciding which medicine is right for them, patients should consider factors such as the specific genetic makeup of their cancer, previous treatments, and the safety and efficacy profile of each medication, in consultation with their healthcare provider.

Difference between Xalkori and Augtyro

Metric	Xalkori (crizotinib)	Augtyro (repotrectinib)
Generic name	Crizotinib	Repotrectinib
Indications	ALK or ROS1-positive non-small cell lung cancer (NSCLC)	Advanced solid tumors with ALK, ROS1, or NTRK1-3 alterations
Mechanism of action	ALK and ROS1 tyrosine kinase inhibitor	ALK, ROS1, and TRK tyrosine kinase inhibitor
Brand names	Xalkori	Augtyro
Administrative route	Oral	Oral
Side effects	Visual disorders, gastrointestinal effects, edema, elevated transaminases, fatigue	Fatigue, constipation, cough, dyspnea, dizziness
Contraindications	Hepatic impairment, concurrent use with strong CYP3A inhibitors or inducers	Not yet fully established; similar contraindications to other tyrosine kinase inhibitors may apply
Drug class	Tyrosine kinase inhibitor	Tyrosine kinase inhibitor
Manufacturer	Pfizer	Turning Point Therapeutics

Efficacy

Xalkori (Crizotinib) Efficacy in Treating Lung Cancer

Xalkori (crizotinib) is an oral medication approved by the Food and Drug Administration (FDA) for the treatment of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive. Clinical trials have demonstrated that crizotinib is effective in shrinking tumors in patients with ALK-positive NSCLC. The efficacy of Xalkori was established in a multicenter, single-arm study where patients with advanced ALK-positive NSCLC who had received prior chemotherapy showed a significant response rate to crizotinib treatment. The response rate was observed through objective response rates (ORR) and progression-free survival (PFS), with many patients experiencing a substantial delay in disease progression.

In addition to its use in previously treated ALK-positive NSCLC, Xalkori has also shown efficacy as a first-line treatment. In a randomized trial comparing crizotinib with standard chemotherapy in untreated advanced ALK-positive NSCLC patients, crizotinib significantly improved progression-free survival, with a median PFS of several months longer than that observed with chemotherapy. The overall response rate was also higher in the crizotinib group compared to the chemotherapy group, indicating a greater likelihood of tumor shrinkage.

Augtyro (Repotrectinib) Efficacy in Treating Lung Cancer

Augtyro (repotrectinib) is an investigational, next-generation tyrosine kinase inhibitor targeting the tropomyosin receptor kinase (TRK), ROS1, and ALK kinases. While not yet approved by the FDA, repotrectinib has shown promise in early clinical trials for the treatment of lung cancer, particularly in patients with ROS1-positive NSCLC and those with ALK-positive NSCLC who have become resistant to prior ALK inhibitors. In these trials, repotrectinib demonstrated a favorable response rate, indicating its potential as an effective treatment option for these patient populations.

Early-phase clinical trials have reported that repotrectinib is well-tolerated and has significant anti-tumor activity in patients with advanced NSCLC harboring ROS1 or ALK rearrangements. The reported data suggest that repotrectinib may offer benefits for patients who have developed resistance to first-generation ALK inhibitors, such as crizotinib, or those who have not previously been treated with an ALK inhibitor. As repotrectinib continues through the clinical development process, further studies will be required to confirm its efficacy and safety profile in a larger cohort of lung cancer patients.

Regulatory Agency Approvals

Xalkori

European Medical Agency (EMA), European Union
Food and Drug Administration (FDA), USA
Health Canada
Pharmaceuticals and Medical Devices Agency (PMDA), Japan
Therapeutic Goods Administration (TGA), Australia

Augtyro

Food and Drug Administration (FDA), USA

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