Alecensa (alectinib)

This study sought primarily to characterize the inhibition effects of four well-known ALK inhibitors, crizotinib, ceritinib, alectinib, and brigatinib, on human UDP-glucuronosyltransferases (UGTs) in vitro and to assess their potential DDI risks in vivo. In vitro-in vivo extrapolation (IVIVE) suggested that all four ALK inhibitors have potential for DDIs due to their inhibitory effects on UGTs. Among them, the DDI risks of alectinib and brigatinib were much higher than the FDA standard, which may have an impact on the safety of clinical drug use.

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

Treatment was then switched to the ALK inhibitor alectinib, and the patient again achieved a partial response. This case suggests that chemotherapy may enrich ALK fusion-positive tumour cell clones through selective pressure. These findings highlight the clinical importance of repeated genetic testing after disease progression and provide new insights for post-resistance treatment strategies.

Among patients with advanced non-small cell lung cancer (NSCLC), ALK-positive disease accounts for roughly 5% of cases We conducted a systematic search of PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov for randomized controlled trials comparing first-line ALK inhibitors with crizotinib or platinum-based chemotherapy and reporting intracranial outcomes. The safety profile was comparable between second- and third-generation ALK TKIs, with alectinib reporting fewer grade ≥3 adverse events (RR 0.72, 95% CI 0.58-0.88). These findings support the use of second- and third-generation ALK TKIs, particularly lorlatinib, as preferred first-line options for patients presenting with brain metastases at diagnosis.

Using alectinib in postoperative adjuvant therapy significantly reduces both the recurrence rate and recurrence-related treatment costs for stage IB (tumor ≥ 4 cm) to IIIA ALK+ NSCLC patients, compared to platinum-based chemotherapy. From perspective of Chinese healthcare system, this approach shows substantial potential for preventing recurrence and achieving cost savings.

Brigatinib was initiated, and a complete radiologic response was documented within 3 months and has been sustained for over 12 months, including durable intracranial disease control. Sustained CR in I1171N-mediated alectinib resistance is rare and highlights the critical role of repeat molecular testing to guide ALK TKI sequencing.

The patient with TRIM24::ALK fusion, following durable responses to alectinib and lorlatinib, relapsed with detection of on-target ALK kinase domain mutations (F1174V, I1171N) and MYC amplification on progression. Comprehensive molecular workup, including RNA-based NGS, is essential for detecting rare but actionable ALK rearrangements and optimizing therapeutic strategy. NGS of CSF was a valuable tool for the detection of clinically suspected leptomeningeal disease and disease monitoring.

We found progressive arthropathy, mostly painless, in one or more joints or intervertebral spaces of patients receiving crizotinib for NSCLC.

This case highlights the value of next-generation sequencing-based profiling in detecting rare actionable alterations missed by standard tests. We also include a discussion on why the EML4-AKL fusion was not detected in the usual test.

The patient received first-line osimertinib combined with pemetrexed/cisplatin, achieving durable disease control for 17 months...Treatment was switched to alectinib, leading to significant tumor regression and partial response. This case illustrates that in triple-positive NSCLC, initial EGFR-TKI combined with chemotherapy can achieve long-term control, while dynamic molecular profiling at progression is essential for identifying resistance mechanisms. Sequential targeted therapy guided by NGS remains a cornerstone for precision management in this complex molecular subtype.

This case demonstrates an exceptionally durable response to first-line alectinib in an ALK-positive LUAD patient with a concurrent rare RET variant. It underscores the long-term efficacy and tolerability of alectinib and highlights the importance of comprehensive genomic profiling in guiding personalized targeted therapy for genetically complex NSCLC.