Alecensa (alectinib)

This case highlights the possibility that alectinib may impair postoperative wound repair. Comprehensive perioperative drug evaluation, multidisciplinary collaboration, and carefully monitored treatment interruption are recommended to maintain the balance between oncologic control and effective tissue healing.

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.

One case harbored an ALK rearrangement, guiding effective targeted therapy with alectinib...Accurate histopathological assessment is essential to establish a correct diagnosis and guide appropriate therapy. A multidisciplinary approach remains the cornerstone of diagnostic precision in CUP cases.

The patient subsequently received palliative systemic chemotherapy with an alectinib-based targeted regimen starting in April 2025, but showed progressive disease on follow-up, even with additional second-line gemcitabine/cisplatin and third-line pembrolizumab therapy. This case highlights that even relatively subtle-appearing lesions require a high index of suspicion for malignancy, emphasizing the importance of early biopsy and comprehensive systemic evaluation. Carcinosarcoma, though rare, should be considered in the differential diagnosis of aggressive tumors arising in atypical locations.

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

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

P2, N=16, Completed, University of Sydney | Active, not recruiting --> Completed

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

The results of the ADAURA trial led to the approval of osimertinib for adjuvant treatment of completely resected, EGFR-mutated NSCLC, while the ALINA trial provided the basis for the approval of alectinib in the adjuvant treatment of ALK-positive, completely resected NSCLC. This article discusses the current evidence regarding the perioperative use of targeted therapies, the recommendations for molecular testing in non-small cell lung cancer, and the resulting therapeutic implications, as well as ongoing research efforts in this evolving field.

This case adds to the limited body of evidence and underscores the importance of recognizing neuroendocrine differentiation in ALK-positive lung cancer cases which show clinical progression. Further studies are needed to elucidate the molecular drivers of this transformation and to optimize treatment strategies for affected patients.

This case illustrates the successful personalization of neoadjuvant alectinib by employing an imaging response-adapted strategy. This strategy utilized dynamic imaging assessments to guide the scheduling of the surgical procedure, culminating in a deep pathological response and prolonged disease-free survival, thereby offering a refined perioperative paradigm for ALK-rearranged NSCLC.

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.