ALK positive

For ALK mutations, the analysis showed that patients with ALK-positive tumors had distinct radiological features, including a higher occurrence in the lower lobes and fewer ground glass nodules compared to the WT group. The study concluded that specific radiological and pathological characteristics, along with EGFR and ALK mutation statuses, could be used to guide the treatment and diagnosis of lung adenocarcinoma.

The patient remains disease-free at 9 months postoperatively. This case highlights the importance of comprehensive molecular testing in ALK-negative IMT and demonstrates that complete surgical resection can achieve excellent outcomes even in rapidly growing lesions.

While the presence of bone, liver, and adrenal metastasis were independent risk factors for OS. Alectinib is recommended over crizotinib in the treatment of patients with ALK-positive NSCLC.

Further analysis revealed that ALK rearrangement was significantly associated with an increased risk of metastasis &lsqb;odds ratio (OR) =2.15; P=0.045], particularly to the bone (OR =5.38; P<0.001) and brain (OR =2.88; P=0.041) after adjusting for confounders. ALK rearrangements were linked to more aggressive histology and increased risk of bone and brain metastases in resected, stage I LUADs, emphasizing the potential relevance of molecular profiling in postoperative risk assessment and treatment planning, even in stage IA patients.

Transition to lorlatinib was associated with extended survival in both groups, reflecting its use as a later-line therapy following resistance. Alectinib demonstrated superior disease control in terms of PFS. Further research is warranted to optimize treatment sequence strategies for ALK inhibitors.

Its recognition is crucial, as ALK-positive ALCL generally responds well to therapy. Further studies are required to better define the clinical and prognostic implications of this presentation.

P2, N=155, Active, not recruiting, Daiichi Sankyo | Trial completion date: Sep 2025 --> Feb 2027

ICIs have become a standard component for resectable stageⅡ-Ⅲ NSCLC, while osimertinib and alectinib established new standards for EGFR- and ALK-positive tumors, respectively. Remaining challenges include optimal patient selection, integration with surgery, and biomarker development. Future directions point to personalized strategies incorporating circulating tumor deoxyribonucleic acid (ctDNA) monitoring and novel therapies to further enhance prognosis in resectable NSCLC.

P1, N=340, Recruiting, AbbVie | N=244 --> 340

We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

Our validation study shows that overly sensitive ALK IHC assays could result in false-positive tumours presenting with difficult-to-read focal or diffusely weak immunoreactivity, which could lead to potential overuse of confirmatory molecular tests. We therefore recommend carefully fine-tuning ALK IHC assays with the D5F3 clone by comparing diagnostic performance with molecular data.

These results, along with the extended intracranial efficacy and consistent safety profile of long-term lorlatinib treatment, are unprecedented in patients with ALK-positive mNSCLC. This Grand Rounds article summarizes the efficacy, safety, and tolerability of lorlatinib after 5 years and includes a fictional patient case to demonstrate how advanced practice providers contribute to personalized patient care and the identification and management of adverse events.