- |||||||||| Alecensa (alectinib) / Roche
Review, Journal: Multisystem ALK-Positive Histiocytosis With DCTN1::ALK (Pubmed Central) - Oct 15, 2024
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.
- |||||||||| Alecensa (alectinib) / Roche
Journal: Appendicitis while on alectinib for non-small cell lung cancer: a tale of two case reports. (Pubmed Central) - Oct 11, 2024
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.
- |||||||||| Alecensa (alectinib) / Roche
Journal: 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 Central) - Oct 6, 2024
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.
- |||||||||| Alecensa (alectinib) / Roche
Biomarker, Journal, Next-generation sequencing: Case Report: Structurally Rare EML4-ALK Identified by Next Generation Sequencing in a Patient with NSCLC with Bilateral Ovarian Metastases. (Pubmed Central) - Sep 30, 2024
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.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca, Alecensa (alectinib) / Roche
Review, Journal, IO biomarker, Metastases: Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario. (Pubmed Central) - Sep 27, 2024
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.
- |||||||||| Alecensa (alectinib) / Roche
Journal: Alectinib in resected ALK-positive non-small-cell lung cancer (Pubmed Central) - Sep 25, 2024
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. No abstract available
- |||||||||| Alecensa (alectinib) / Roche
Journal: Successful treatment of a non-small-cell lung cancer patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del with alectinib. (Pubmed Central) - Sep 25, 2024
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.
- |||||||||| Alecensa (alectinib) / Roche
Journal, Metastases: Diagnostic and Therapeutic Implications of a FUS::TFCP2 Fusion and ALK Activation in a Metastatic Rhabdomyosarcoma. (Pubmed Central) - Sep 21, 2024
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.
- |||||||||| Phase classification, Metastases: ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma (clinicaltrials.gov) - Sep 20, 2024
P2, N=90, Recruiting,
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. Phase classification: P --> P2
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: A narrative review on perioperative systemic therapy in non-small cell lung cancer. (Pubmed Central) - Sep 17, 2024
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.
- |||||||||| Retrospective data, Review, Journal, Metastases: Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-na (Pubmed Central) - Sep 12, 2024
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-na
- |||||||||| Lorbrena (lorlatinib) / Pfizer
Journal: Complete and durable regression of leptomeningeal involvement during lorlatinib treatment in a patient with lung cancer. (Pubmed Central) - Sep 11, 2024
Third-line lorlatinib was then administered, and 2?months later encephalic MRI documented complete regression of the leptomeningeal involvement that is still maintained after 36?months while treatment with lorlatinib is still ongoing with good tolerability. To the best of our knowledge, this is the longer intracranial response reported in the literature, underlining the importance of the most appropriate choice of systemic treatments and their integration with loco-regional approaches to improve outcomes.
- |||||||||| Alecensa (alectinib) / Roche
MUCINOUS LUNG ADENOCARCINOMA PRESENTING AS A HEMORRHAGIC PLEURAL EFFUSION (Convention Center Exhibit Hall: Poster Area 3) - Sep 11, 2024 - Abstract #CHEST2024CHEST_6609;
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.
- |||||||||| Cilcane (cilengitide) / Iceni Pharma, Tabrecta (capmatinib) / Novartis, Alecensa (alectinib) / Roche
Journal: Cancer-associated fibroblasts confer ALK inhibitor resistance in EML4-ALK -driven lung cancer via concurrent integrin and MET signaling. (Pubmed Central) - Sep 10, 2024
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.
- |||||||||| Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Journal, HEOR, Real-world evidence, Real-world, Metastases: Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK-positive advanced non-small cell lung cancer. (Pubmed Central) - Sep 7, 2024
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. In this large real-world study, TTD2 and the total time on sequential ALK TKIs was approximately 2.5
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Vizimpro (dacomitinib) / Pfizer
Trial completion, Enrollment change, Trial completion date, Trial primary completion date, Metastases: DELINOR: A Study to Learn About the Effectiveness of Cancer Medicines in Patients With Metastatic Non-small Cell Lung Cancer in Norway. (clinicaltrials.gov) - Sep 4, 2024
P=N/A, N=1, Completed,
These data support the use of lorlatinib as a first-line treatment for ALK+ advanced/metastatic NSCLC. Recruiting --> Completed | N=20605 --> 1 | Trial completion date: Feb 2025 --> Jan 2024 | Trial primary completion date: Feb 2025 --> Jan 2024
- |||||||||| Alecensa (alectinib) / Roche
Journal: Redefining Recovery: The Transformative Impact of the ALINA Trial on Adjuvant Therapy for ALK-Positive Non-Small Cell Lung Cancer. (Pubmed Central) - Sep 3, 2024
This approval was grounded in the outcomes of the ALINA trial, which demonstrated that alectinib significantly enhances disease-free survival compared to traditional platinum-based chemotherapy in the adjuvant setting. The ALINA trial is notable not just for advancing ALK tyrosine kinase inhibitors (TKIs) into the adjuvant setting but also for its innovative approach of comparing them to adjuvant chemotherapy, distinguishing it from other landmark trials.
- |||||||||| Review, Journal, Checkpoint inhibition, PD(L)-1 Biomarker, Checkpoint block: Early-Stage Non-Small Cell Lung Cancer: New Challenges with Immune Checkpoint Blockers and Targeted Therapies. (Pubmed Central) - Aug 31, 2024
Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR- and ALK-positive NSCLC, respectively, changing the standard of care in these subgroups...In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC...Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC.
- |||||||||| Journal: Targeting ALK receptors in non-small cell lung cancer: what is the road ahead? (Pubmed Central) - Aug 20, 2024
Second- and third-generation ALK inhibitors (alectinib, brigatinib, and lorlatinib) offer to NSCLC patients a clinically meaningful prolongment of survival with a very good quality of life profile...Very recently, alectinib has been demonstrated to improve efficacy outcomes compared with chemotherapy also in resected stage IB-IIIA ALK-rearranged NSCLC, extending the clinical benefit offered by ALK inhibitors also to the adjuvant setting. Future development of ALK inhibitors in NSCLC treatment includes the search for optimal management of acquired resistance to first-line treatments and the extension of use of ALK inhibitors also to neoadjuvant and preferably to perioperative setting.
- |||||||||| Alecensa (alectinib) / Roche
Dysphagia As a Presenting Symptom of An Aggressive Adenocarcinoma of Lung In a Female (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_1094;
They were successfully transitioned to an oral regimen with Alectinib...Figure: Near complete resolution of the right-sided lung mass is appreciated with a notable reduction in the size of the mediastinal mass. Specifically, the measurements decreased from the initial size of 58 x 73mm to 30 x 31mm as demonstrated by the image on the left (initial CT scan) and the image on the right (CT at 3 month follow-up)
- |||||||||| Alecensa (alectinib) / Roche
Enrollment closed, Trial completion date, Trial primary completion date, Metastases: ALNEO: Alectinib in Neo-adjuvant Treatment of Stage III NSCLC (clinicaltrials.gov) - Aug 9, 2024
P2, N=33, Active, not recruiting,
Patients on alectinib had reduced EMA binding. Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2023 --> Dec 2024
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