Alecensa (alectinib)

The association between the docking predictions and clinical outcomes corroborates the utility of computational modeling for tailoring therapies, although the structural models provide mechanistic insight into drug efficacy against these rare mutations. The present integrated approach emphasizes the value of merging in silico methods into clinical decision-making to overcome the therapeutic uncertainty of uncommon oncogenic driver alterations.

Alectinib is the first ALK inhibitor to show a consistent DFS benefit over chemotherapy in patients with resected early-stage ALK-positive NSCLC, regardless of disease stage per AJCC/UICC 7th or 8th edition, nodal status, or tumor size.

In this study, there was no significant difference in the therapeutic effect of alectinib by ALK fusion variants. This finding indicates that alectinib may be an effective treatment option even for patients with V3.

The patient received two cycles of nab-paclitaxel and carboplatin, and repeated CT scan showed disease progression. Her treatment was subsequently changed to glumetinib plus iruplinalkib and she died less than one month later...Co-amplification of the multiple genes may be involved in aggressive disease and drug resistance, which should be considered in future clinical trials and clinical management. Early broad-panel next-generation sequencing testing in LUSCC patients who are never-smokers may help guide management for patients who have complex mutational profiles.

Disproportionality analyses were performed using four algorithms-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS)-to detect adverse event signals for crizotinib, alectinib, and brigatinib. All three ALK-TKIs demonstrate distinct, generation-dependent safety profiles characterized by early-onset hepatobiliary and pulmonary toxicities, with evident sex-specific differences in organ susceptibility. Intensive safety monitoring during the initial 12 weeks of therapy is essential for preventing severe outcomes.

Targeted therapy with the CNS-penetrant ALK inhibitor alectinib induced rapid clinical improvement and significant radiographic regression. This case highlights the diagnostic pitfalls of CNS ALCL, emphasizes the necessity of early biopsy in atypical lesions, and demonstrates the transformative potential of molecularly targeted therapies for rare neuro-oncological malignancies.

In this phase IV open-label study, patients with ALK-positive metastatic NSCLC that progressed on first-line alectinib or ceritinib received lorlatinib 100 mg once daily. Lorlatinib continued to show clinically meaningful benefit in patients with previously treated ALK-positive metastatic NSCLC. clinicaltrials.gov identifier is NCT04362072.

P1/2, N=11, Active, not recruiting, Hoffmann-La Roche | Phase classification: P3 --> P1/2 | Trial completion date: Mar 2033 --> Aug 2026 | Trial primary completion date: Jun 2028 --> Aug 2026

P1/2, N=45, Recruiting, Instituto Nacional de Cancerologia de Mexico | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P1/2, N=56, Recruiting, Joshua Palmer | Trial completion date: Jun 2027 --> Feb 2029 | Trial primary completion date: Jun 2026 --> Feb 2028

After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (EGFR) mutant and anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC), also combined with a progressively better safety profile, from chemotherapy to new generation tyrosine kinase inhibitors (TKIs) (osimertinib, alectinib, brigatinib), the recent MARIPOSA and CROWN trials have changed this trend. The story would be easy and totally positive if these two innovative, amazing treatments were not associated with new peculiar features in safety profiles that must be discussed with patients, because they potentially affect their quality of life. When treating these patient populations, the peculiar safety profiles of amivantamab plu lazertinib and lorlatinib require a well-structured shared decision making, "where and when", both the high probability of a longer survival and the risk of worse quality of life must be well announced and explained to our patients before the shared final treatment choice.