Xalkori (crizotinib)

This ADP-ribosylation-based prognostic model reliably predicts LUAD survival and identifies potential biomarkers for tailored therapy.

While second- and third-generation ALKi (including alectinib, brigatinib, ensartinib, envonalkib, and lorlatinib) have demonstrated superior efficacy compared with the first-generation inhibitor crizotinib in randomized trials, the absence of direct head-to-head comparisons limits the definition of their relative clinical benefit. This indirect comparison indicates that lorlatinib provides the most durable PFS and the strongest intracranial disease control, although ALKis are characterized by distinct toxicity profiles. In the absence of clear OS differences at present, first-line treatment selection should integrate efficacy, intracranial activity, tolerability, and emerging molecular features within a personalized therapeutic framework.

P3, N=50, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | N=200 --> 50 | Trial completion date: May 2026 --> Sep 2025 | Trial primary completion date: May 2026 --> Sep 2025

Tumor burden was prognostic and predictive in ALK-positive NSCLC. Treatment intensification may benefit patients with high tumor burden.

This first documented case demonstrates the therapeutic efficacy of crizotinib in ALK-IR rearranged NSCLC, emphasizing the importance of comprehensive molecular profiling in guiding precision oncology.

The patient was treated with the oral targeted drug crizotinib and died of multiple organ failure 18 months after surgery...UIMT and EIMS that exhibit aggressive behavior typically possess a greater number of genetic alterations. The abnormal expression of p53 or p16 protein, when combined with clinicopathological parameters, can serve as indicators for predicting the adverse biological behavior of tumors.

Despite robust evidence supporting ALK-targeted therapies, this study highlights substantial disparities in access to diagnostics and treatment for ALK-rearranged NSCLC in Brazil, particularly among patients reliant on the public health care system. Findings underscore the need for policies to strengthen testing infrastructure, ensure equitable access to guideline-recommended therapies, and enhance provider education. Addressing these gaps is essential for equitable precision oncology and improved outcomes.

Upon light irradiation, the caged compound undergoes efficient uncaging to release active Crizotinib, restoring its potent kinase inhibitory and antiproliferative activities. This work establishes BODIPY-caged Crizotinib as a promising photoactivatable agent for precision cancer therapy.

During treatment, reducing crizotinib dosage does not lead to recurrence of lung cancer while minimizing complications. The case underscores the necessity of integrating imaging and pathological features in the diagnostic process, alongside the need for personalized adjustments and development of treatment plans tailored to each patient.

With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented long-term benefit in patients with advanced ALK-positive NSCLC. Patients without progression within 24 months on lorlatinib have a low risk of progression or death at year 7 and may continue long-term treatment. Findings suggest that sustained long-term disease control with first-line lorlatinib may enable advanced ALK-positive NSCLC to evolve toward a chronic condition.

This exploratory study identified WDR17 as a candidate biomarker associated with TKI resistance in lung adenocarcinoma, potentially involved in maintaining protein homeostasis and metabolic balance. These preliminary findings warrant validation in larger, independent cohorts.

P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: May 2026 --> Jun 2027