^
4d
A phase I-III, multicenter study evaluating the efficacy and safety of multiple therapies in cohorts of patients with resectable stage I-III non-small cell lung cancer, selected according to biomarker status (ChiCTR2400090972)
P2, N=150, Not yet recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci
New P2 trial
|
ALK (Anaplastic lymphoma kinase)
|
ALK fusion
|
FoundationOne® CDx
|
Alecensa (alectinib)
8d
Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK-Positive NSCLC. (PubMed, JTO Clin Res Rep)
The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.
Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK positive • ALK fusion • ALK V3a
|
Alecensa (alectinib)
9d
A real-world retrospective study to assess efficacy and safety of alectinib as adjuvant therapy in IB-IIIB NSCLC patients harboring ALK rearrangement. (PubMed, Front Oncol)
Alectinib, as adjuvant therapy, demonstrated favorable efficacy and manageable safety in patients with completely resected ALK-positive stage I B-IIIB non-small cell lung cancer. A limitation of this study is the small sample size, and a larger-scale real-world sample study is needed to further evaluate the efficacy and safety of alectinib as adjuvant therapy.
Retrospective data • Journal • Real-world evidence • Real-world
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement
|
Alecensa (alectinib)
14d
Enrollment closed
|
BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden)
|
Avastin (bevacizumab) • cisplatin • Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • carboplatin • gemcitabine • Rozlytrek (entrectinib) • docetaxel • Alecensa (alectinib) • Cotellic (cobimetinib) • pemetrexed • divarasib (RG6330)
14d
HORIZON 2: A Study to See How Well and How Safely Different Treatments Work in a Group of Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P2, N=150, Not yet recruiting, Hoffmann-La Roche | Trial completion date: Nov 2034 --> Mar 2033 | Trial primary completion date: Oct 2029 --> Jun 2028
Trial completion date • Trial primary completion date
|
cisplatin • carboplatin • Alecensa (alectinib) • pemetrexed
15d
Long-Term Response of Lorlatinib to Leptomeningeal Metastasis in Patients with Anaplastic Lymphoma Kinase Fusion Positive Non-Small Lung Cancer: A Case Report. (PubMed, Case Rep Oncol)
In further analysis, lorlatinib revealed superior intracranial efficacy and prolonged time to intracranial progression compared with crizotinib. Herein, we report a case of ALK-positive NSCLC with leptomeningeal metastasis that was successfully treated with lorlatinib after progression to brigatinib and alectinib. This case demonstrates the potential of lorlatinib in managing leptomeningeal metastasis in ALK-positive NSCLC. The case suggests a paradigm shift in therapeutic approaches for CNS metastasis, including brain and leptomeningeal metastases.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement • ALK fusion
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)
24d
ALK-tyrosine kinase inhibitor intrinsic resistance due to de novo MET-amplification in metastatic ALK-rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination-case report. (PubMed, Transl Lung Cancer Res)
A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant 1 (EML4-ALK v.1) and TP53 co-mutation, displayed only mixed response after three months and highly symptomatic progression after 6 months of first-line brigatinib treatment. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment.
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4)
|
TP53 mutation • MET amplification • ALK rearrangement • MET overexpression • ALK fusion • MET expression
|
Xalkori (crizotinib) • Alecensa (alectinib) • Alunbrig (brigatinib)
26d
Targeted and cytotoxic inhibitors used in the treatment of lung cancers. (PubMed, Pharmacol Res)
On the order of 20% of NSCLCs bear activating mutations in EGFR and are treated with osimertinib and other kinase antagonists...Local treatment options to control thoracic disease include radiotherapy and surgery. In patients with extensive-stage disease, a platinum agent (cisplatin or carboplatin) combined with etoposide and an anti-PDL1 inhibitor (atezolizumab or durvalumab) for four cycles followed by anti-PDL1 maintenance therapy is the recommended first-line regimen.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
|
EGFR mutation • BRAF mutation • ALK translocation
|
Mekinist (trametinib) • cisplatin • Tagrisso (osimertinib) • Tecentriq (atezolizumab) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Retevmo (selpercatinib) • pemetrexed • etoposide IV • Tabrecta (capmatinib)
28d
Real-World Data Presenting the Descriptive Analysis of the Use of Tyrosine Kinase Inhibitors (TKIs) Among Metastatic Non-Small-Cell Lung Cancer (mNSCLC) Patients in Qatar: A Nationwide Retrospective Cohort Study. (PubMed, Clin Med Insights Oncol)
The TKIs used during this period include EGFR inhibitors such as afatinib, erlotinib, gefitinib, and osimertinib and ALK inhibitors such as alectinib and crizotinib. The EGFR-targeted and ALK-targeted therapies appear to have acceptable clinical response rate and safety profile in our population. Close and frequent monitoring of adverse events is advised to ensure a good quality of life and prevent serious complications.
Retrospective data • Journal • Real-world evidence • Real-world • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement
|
Xalkori (crizotinib) • Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Alecensa (alectinib)
29d
NRG-LU003: Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025
Trial completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
ALK positive • MET amplification • ALK rearrangement
|
cisplatin • Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • pemetrexed • Alunbrig (brigatinib) • Ensacove (ensartinib)
1m
Multisystem ALK-Positive Histiocytosis With DCTN1::ALK Fusion in an Adult, Responsive to Alectinib: Case Report and Literature Review. (PubMed, J Cutan Pathol)
ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • DCTN1 (Dynactin Subunit 1) • ALK1 (Activin A Receptor Like Type 1) • CD68 (CD68 Molecule)
|
ALK positive • ALK fusion • DCTN1-ALK fusion
|
Alecensa (alectinib)
1m
Cardiovascular toxicity of anaplastic lymphoma kinase inhibitors for patients with non-small cell lung cancer: a network meta-analysis. (PubMed, Future Oncol)
Aim: We conducted network meta-analysis to assess cardiovascular toxicity of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs).Materials & Eleven articles involving 2855 patients and six interventions including crizotinib, alectinib, ceritinib, lorlatinib, brigatinib and chemotherapy were analyzed. No significant difference was observed in overall cardiovascular risk among ALK-TKIs. For vascular toxicity, crizotinib and ceritinib had a higher risk of thrombotic events than brigatinib. Crizotinib and lorlatinib were more likely to cause blood pressure abnormalities. Clinicians should carefully monitoring cardiovascular events when ALK-TKIs used in NSCLCs patients with baseline cardiovascular diseases.
Retrospective data • Review • Journal
|
ALK (Anaplastic lymphoma kinase)
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
1m
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Alecensa (alectinib)
1m
Taiwan Nationwide Study of First-Line ALK-TKI Therapy in ALK-Positive Lung Adenocarcinoma. (PubMed, Target Oncol)
For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
1m
Appendicitis while on alectinib for non-small cell lung cancer: a tale of two case reports. (PubMed, Front Oncol)
Her symptoms continued despite an antibiotic course with re-imaging concerning for acute appendicitis, which was successfully treated with appendectomy and amoxicillin-clavulanic acid. Both patients remained on alectinib over the courses of appendicitis without interruption. While appendicitis has not been previously described as an adverse effect of alectinib, its incidence in two patients at our center within several months following the administration of alectinib raises its suspicion as a possible adverse effect.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Alecensa (alectinib)
1m
Combined blockade of GPX4 and activated EGFR/HER3 bypass pathways inhibits the development of ALK-inhibitor-induced tolerant persister cells in ALK-fusion-positive lung cancer. (PubMed, Mol Oncol)
We generated alectinib-induced DTP cells from a patient-derived ALK+ non-small-cell lung cancer (NSCLC) cell line and screened 3114 agents in the anticancer compounds library (TargetMol)...Triple combination with an ALK-TKI plus a bypass pathway inhibitor plus a GPX4 inhibitor suppressed cell growth and induced intracellular ROS accumulation more greatly than did treatment with each agent alone. The combined inhibition of ALK plus inhibition of activated bypass signals plus inhibition of GPX4 may be a potent therapeutic strategy for patients with ALK+ NSCLC to prevent the development of resistance to ALK-TKIs and lead to tumor eradication.
Journal
|
ALK (Anaplastic lymphoma kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • GPX4 (Glutathione Peroxidase 4)
|
ALK positive • ALK fusion
|
Alecensa (alectinib)
1m
Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC). (PubMed, Lung Cancer)
Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.
Retrospective data • Review • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)
1m
New P2 trial
|
cisplatin • carboplatin • Alecensa (alectinib) • pemetrexed
1m
Trial completion
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement
|
Alecensa (alectinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
1m
Correlation between ALK+ non-small cell lung cancer targeted therapy and thrombosis: a systematic review and network meta-analysis. (PubMed, BMJ Open)
Compared with chemotherapy, alectinib, lorlatinib, brigatinib and ceritinib, crizotinib significantly increased the risk of TE and VTE.
Clinical • Retrospective data • Review • Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
2ms
Case Report: Structurally Rare EML4-ALK Identified by Next Generation Sequencing in a Patient with NSCLC with Bilateral Ovarian Metastases. (PubMed, Onco Targets Ther)
Despite two cycles of adjuvant chemotherapy consisting of carboplatin and gemcitabine, CT revealed that the pleural effusion had increased from it before chemotherapy, and the shortness of breath worsened...Treatment with alectinib, a second-generation ALK-tyrosine kinase inhibitor, led to a partial response of 18 months' duration, and the shortness of breath improved...Variations in the drug response among EML4-ALK fusion variants highlight the importance of understanding their molecular structure. Further investigation is warranted to refine fusion gene detection methods and assess the therapeutic implications of rare fusion variants.
Journal • Next-generation sequencing
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK rearrangement • EML4-ALK fusion • ALK fusion • EML4-ALK rearrangement
|
carboplatin • gemcitabine • Alecensa (alectinib)
2ms
Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario. (PubMed, Curr Oncol)
To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB-IIIA (TNM 7th edition)...In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)-IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.
Review • Journal • IO biomarker • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement
|
Tagrisso (osimertinib) • Alecensa (alectinib)
2ms
Successful treatment of a non-small-cell lung cancer patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del with alectinib. (PubMed, Thorac Cancer)
However, in recent years the use of next-generation sequencing (NGS) in clinical laboratories has become increasingly widespread, identifying a lot of new ALK fusion partners as well as a large quantity of co-occurring genomic alterations. Unfortunately, the growing number of genomic alterations detected by NGS does not always correspond to adequate knowledge of their clinical significance, often resulting in an empiric treatment of patients harboring uncommon mutations.
Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • HIP1 (Huntingtin Interacting Protein 1)
|
ALK rearrangement • ALK fusion
|
Alecensa (alectinib)
2ms
Trial completion
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement
|
FoundationOne® CDx • VENTANA ALK (D5F3) CDx Assay
|
Xalkori (crizotinib) • Alecensa (alectinib) • Alunbrig (brigatinib)
2ms
A novel molecular target, superoxide dismutase 1, in ALK inhibitor-resistant lung cancer cells, detected through proteomic analysis. (PubMed, Exp Cell Res)
SOD1 overexpression is thought to be a mechanism for alectinib resistance, suggesting the possibility of overcoming resistance using SOD1 inhibitors.
Journal • BRCA Biomarker • PARP Biomarker
|
ALK (Anaplastic lymphoma kinase) • BRCA1 (Breast cancer 1, early onset)
|
BRCA1 mutation • ALK positive
|
Alecensa (alectinib)
2ms
AXL and SHC1 confer crizotinib resistance in patient-derived xenograft model of ALK-driven lung cancer. (PubMed, iScience)
To discover therapeutic targets to overcome crizotinib resistance (CR), we generated patient-derived xenograft CR mice and subjected them to phosphorylation profiling, together with CR mice treated with ASP3026 or alectinib. We also found that SHC1 phosphorylation was increased in CR mice and SHC1 knockdown sensitized ALK-driven cells to crizotinib. Our study provides a new view of signaling pathways leading to CR, suggesting AXL and SHC1 as potential targets for combination therapy to overcome CR.
Preclinical • Journal
|
ALK (Anaplastic lymphoma kinase) • AXL (AXL Receptor Tyrosine Kinase)
|
ALK rearrangement
|
Xalkori (crizotinib) • Alecensa (alectinib) • ASP-3026
2ms
Diagnostic and Therapeutic Implications of a FUS::TFCP2 Fusion and ALK Activation in a Metastatic Rhabdomyosarcoma. (PubMed, Genes Chromosomes Cancer)
This patient displayed a rapid and dramatic clinical and radiographic response to an ALK inhibitor, alectinib. Unfortunately, the response was short-lived, likely due to the advanced stage and aggressiveness of the disease. This report describes genome and transcriptome characterization of an intraosseous rhabdomyosarcoma, few of which exist in the literature, as well as providing evidence that inhibition of ALK may be a rational treatment strategy for patients with this exceedingly rare soft tissue sarcoma subtype characterized by TFCP2 fusions and ALK activation.
Journal • Metastases
|
FUS (FUS RNA Binding Protein) • TFCP2 (Transcription Factor CP2)
|
ALK fusion
|
Alecensa (alectinib)
2ms
ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma (clinicaltrials.gov)
P2, N=90, Recruiting, Hunan Province Tumor Hospital | Phase classification: P --> P2
Phase classification • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • carboplatin • paclitaxel • Alecensa (alectinib) • Lorbrena (lorlatinib) • pemetrexed • Alunbrig (brigatinib)
2ms
Alectinib maintenance therapy following cord blood transplantation for relapsed pediatric anaplastic large cell lymphoma with central nervous system involvement. (PubMed, Ann Hematol)
The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Alecensa (alectinib)
2ms
Alectinib Versus Crizotinib in Asian Patients With Treatment-Naïve Advanced ALK-Positive NSCLC: Five-Year Update From the Phase 3 ALESIA Study. (PubMed, JTO Clin Res Rep)
No new safety signals were observed. With four additional years of follow-up, these updated results confirm the clinical benefit and manageable safety of alectinib in Asian patients with advanced ALK-positive NSCLC, and confirm alectinib as a standard-of-care treatment for patients with advanced ALK-positive NSCLC.
P3 data • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib)
2ms
Epithelioid inflammatory myofibroblastic sarcoma treated with Alectinib: a case report and literature review. (PubMed, Front Oncol)
After a comprehensive assessment and symptomatic treatment, her condition stabilized, leading to a favorable prognosis. This study summarizes cases of abdominal EIMS, highlights the successful use of Alectinib for treatment, and discusses the management of medication-related complications.
Review • Journal
|
ALK (Anaplastic lymphoma kinase)
|
Alecensa (alectinib)
2ms
A narrative review on perioperative systemic therapy in non-small cell lung cancer. (PubMed, Explor Target Antitumor Ther)
Adjuvant atezolizumab in NSCLC first demonstrated a clinical benefit with an immune checkpoint inhibitor. Then, with studies studying a significant benefit in major pathologic response in surgical patients treated preoperatively with immunotherapy compared to only chemotherapy, neoadjuvant nivolumab and chemotherapy were evaluated and showed significant event-free survival benefit leading to subsequent studies evaluating perioperative immunotherapy and chemotherapy. Meanwhile, with regards to targeted therapies, adjuvant osimertinib in EGFR-mutated NSCLC and adjuvant alectinib in ALK-rearranged NSCLC have both received regulatory approvals following demonstrated clinical benefit in clinical trials...Furthermore, circulating tumor DNA and studies looking at better tools to prognosticate immunotherapy response will help with decision-making regarding which patients should receive immunotherapy and if so, either only pre-operatively or both pre- and post-operatively. In this review, we look at the evolution of systemic therapy in the perioperative setting from adjuvant chemotherapy to adjuvant immunotherapy to perioperative immunotherapy and look at perioperative targeted therapy while looking ahead to future considerations.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
EGFR mutation • ALK rearrangement
|
Opdivo (nivolumab) • Tagrisso (osimertinib) • Tecentriq (atezolizumab) • Alecensa (alectinib)
2ms
Intraosseous spindle cell rhabdomyosarcoma with FET (EWSR1)- TFCP2 and LOC101929418-ALK fusions: a case report and literature review (ECP 2024)
After unsuccessful chemotherapy, Alectinib (ALK inhibitor) combined with radiotherapy was initiated... Intraosseous spindle cell rhabdomyosarcoma (RMS) with TFCP2 rearrangement is a highly aggressive tumour with an early onset, fast progression and poor response to standard therapies. Our case, one of the few cases described with two gene fusions, contributes to understanding its molecular profile. Further clinical studies are required to explore the efficacy of targeted therapy for ALK and for the development of new effective treatment approaches.
Review • Clinical • Case report
|
EWSR1 (EWS RNA Binding Protein 1) • TFCP2 (Transcription Factor CP2) • MYOD1 (Myogenic Differentiation 1) • NCOA2 (Nuclear Receptor Coactivator 2)
|
ALK fusion
|
Archer® FusionPlex® Sarcoma kit • FusionPlex® Dx
|
Alecensa (alectinib)
2ms
Coexistence of acute severe leukocytosis and anaplastic lymphoma kinase‑positive histiocytic sarcoma, a rare entity with an unusual presentation: A case report. (PubMed, Oncol Lett)
The patient initially responded to crizotinib but required alectinib due to central nervous system progression. The patient has shown a near-complete response and remained stable for 2 years; however, there has been recent lymph node progression.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib)
2ms
A novel secondary ALK gene mutation which resistant to second-generation TKIs: a case report and literature review. (PubMed, Front Oncol)
We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib...Ensartinib and ceritinib were administered as second-line and third-line treatments...The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
|
ALK positive • ALK fusion • ALK mutation • ALK V1180L
|
Alecensa (alectinib) • Zykadia (ceritinib) • Ensacove (ensartinib)
2ms
Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis. (PubMed, Transl Lung Cancer Res)
Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. Next-generation ALK inhibitors had better efficacy than crizotinib in the treatment of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC. Iruplinalkib may have more favorable PFS benefit than other ALK inhibitors for Asians.
Retrospective data • Review • Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib) • Ensacove (ensartinib) • Qi Xinke (iruplinalkib) • Anluoqing (envonalkib)
2ms
MUCINOUS LUNG ADENOCARCINOMA PRESENTING AS A HEMORRHAGIC PLEURAL EFFUSION (CHEST 2024)
With the presence of the ALK rearrangement, the patient was started on alectinib...The patient subsequently underwent three cycles of carboplatin/pemetrexed, and ultimately transitioned to hospice care and passed away fourteen months after initial diagnosis... Mucinous adenocarcinoma is an uncommon histological subtype of lung adenocarcinoma with a poor prognosis, with patients often presenting at a later disease stage with complications which may include malignant pleural effusions.
PD(L)-1 Biomarker • IO biomarker • Pleural effusion
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • NKX2-1 (NK2 Homeobox 1) • NAPSA (Napsin A Aspartic Peptidase)
|
PD-L1 expression • PD-L1 overexpression • ALK rearrangement
|
PD-L1 IHC 22C3 pharmDx • NeoTYPE® Lung Tumor Profile
|
carboplatin • Alecensa (alectinib) • pemetrexed
2ms
Disease characteristics and treatment outcomes in patients with resected early-stage ALK+ non-small cell lung cancer from ALINA, a phase III randomized trial of adjuvant alectinib vs. chemotherapy (AATS-ITSOS 2024)
P3 | "Alectinib is the first ALK inhibitor to show a consistent DFS benefit across lymph node stages with a manageable safety profile, and is an effective new treatment strategy for patients with resected ALK+ NSCLC."
P3 data • Clinical
|
Alecensa (alectinib)
2ms
Breakfast Symposium: Alecensa (alectinib) - New Indication based on Results from the Phase III ALINA Study | Sponsored by: Genentech (non-CME) (AATS-ITSOS 2024)
"Sponsored by: Genentech (non-CME) This session will provide a comprehensive overview of Alecensa and the indication in ALK positive NSCLC based on the Phase III ALINA study results. Attendees will gain insights into the study design, efficacy and safety and the clinical significance of Alecensa in reducing the risk of disease recurrence or death in ALK positive NSCLC patients."
P3 data
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Alecensa (alectinib)
2ms
Cancer-associated fibroblasts confer ALK inhibitor resistance in EML4-ALK -driven lung cancer via concurrent integrin and MET signaling. (PubMed, bioRxiv)
Consistently, combination of the ALK TKI alectinib with the MET TKI capmatinib and/or the integrin inhibitor cilengitide was significantly more efficacious than single agent treatment in suppressing tumor growth using an in vivo EML4-ALK -dependent allograft mouse model of NSCLC. In summary, these findings emphasize the complexity of resistance-associated crosstalk between CAFs and cancer cells, which can involve multiple concurrent signaling pathways, and illustrate how comprehensive elucidation of paracrine and juxtacrine resistance mechanisms can inform on more effective therapeutic approaches.
Journal
|
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • ITGB1 (Integrin Subunit Beta 1)
|
EML4-ALK fusion • ALK fusion
|
Alecensa (alectinib) • Tabrecta (capmatinib) • Cilcane (cilengitide)
2ms
Long-term survival following molecular-targeted therapy for intramedullary non-small-cell lung cancer metastasis. (PubMed, Surg Neurol Int)
At present, 14 years after the original ICSM surgery, the patient remains disease free but continued alectinib (Karnofsky Performance Scale: 90%). Although the prognosis for ICSM is generally poor, molecular-targeted therapies, such as alectinib, as administered in this case, may provide long-term survival for patients with ALK-positive NSCLC tumors.
Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK rearrangement
|
Alecensa (alectinib)
2ms
Comparative Efficacy and Safety of Lorlatinib Versus Alectinib and Lorlatinib Versus Brigatinib for ALK-Positive Advanced/Metastatic NSCLC: Matching-Adjusted Indirect Comparisons. (PubMed, Clin Lung Cancer)
Lorlatinib was estimated to have superior efficacy over first- and second-generation ALK-TKIs, but a higher rate of Grade ≥3 AEs compared to alectinib. These data support the use of lorlatinib as a first-line treatment for ALK+ advanced/metastatic NSCLC.
Journal • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive
|
Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)