- |||||||||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Journal: The potential role of HGF-MET signaling and autophagy in the war of Alectinib versus Crizotinib against ALK-positive NSCLC. (Pubmed Central) - May 11, 2019 However, given the potential relevance of HGF-MET signaling and especially autophagy to the war against ALK-positive NSCLC between Alectinib and Crizotinib, it's too early to reach a convincing conclusion. Therefore, to further improve the therapeutic efficacy of ALK-positive NSCLC, this commentary highlights the negligence in design of relevant clinical trials, emphasizes the importance of molecular characteristics investigation, and discusses the prospect of combination therapy.
- |||||||||| Biomarker, Journal, PD(L)-1 Biomarker, IO Biomarker: Tissue and Blood Biomarkers in Lung Cancer: A Review. (Pubmed Central) - May 2, 2019
For predicting response to single agent pembrolizumab in the first-line treatment of patients with advanced adenocarcinoma or squamous cell NSCLCs, PD-L1 should be measured by an approved assay (e.g., PD-L1 IHC 22C3 pharmDx method)...Serum biomarkers may also be of use in determining prognosis and monitoring response to systemic therapies. With the increasing use of biomarkers, personalized treatment especially for patients with adenocarcinoma-type NSCLC is finally on the horizon.
- |||||||||| Clinical, Journal: Treatment of ALK-positive nonsmall cell lung cancer: recent advances. (Pubmed Central) - Apr 26, 2019
Our review will discuss the recent phase III data with ceritinib and alectinib as well as clinical trials with other ALK inhibitors. We will also address two important issues in the management of ALK-positive NSCLC, prevention and treatment of brain metastases and management of emergent ALK-TKI resistance mechanisms.
- |||||||||| Alecensa (alectinib) / Roche
Journal: A Molecular Dynamics Investigation into the Mechanisms of Alectinib Resistance of Three ALK Mutants. (Pubmed Central) - Apr 19, 2019 The "key and lock mechanism" between the ethyl group at position 9 of alectinib and a recognition cavity in the hinge region of ALK is presented to illustrate the major molecular origin of drug resistance. Our results provide mechanistic insight into the effect of ALK mutations resistant to alectinib, which could contribute to further rational design of inhibitors to combat the acquired resistance.
- |||||||||| Alecensa (alectinib) / Roche
Journal: VIT-ALK, a Novel Alectinib-Sensitive Fusion Gene in Lung Adenocarcinoma. (Pubmed Central) - Apr 19, 2019 Our results provide mechanistic insight into the effect of ALK mutations resistant to alectinib, which could contribute to further rational design of inhibitors to combat the acquired resistance. No abstract available
- |||||||||| Alecensa (alectinib) / Roche
Clinical, Journal, Real-World Evidence: Safety and effectiveness of alectinib in a real-world surveillance study in patients with ALK-positive NSCLC in Japan. (Pubmed Central) - Apr 18, 2019 The 18-month cumulative OS rate was longer in patients with ECOG performance status ≤1 (versus 2 or ≥3; 83.7% versus 44.5% or 27.2%), without prior crizotinib (versus with; 81.1% versus 73.4%), receiving first-line alectinib (versus second and third or later line; 83.0% versus 79.2% or 71.9%), without brain metastases (versus with; 79.5% versus 71.5%). These data confirm the favorable safety and effectiveness of alectinib in patients with ALK-positive NSCLC in Japan.
- |||||||||| Clinical, Review, Journal: Lung Toxicity in Non-Small-Cell Lung Cancer Patients Exposed to ALK Inhibitors: Report of a Peculiar Case and Systematic Review of the Literature. (Pubmed Central) - Apr 10, 2019
...Crizotinib was responsible for pulmonary adverse events (AEs) in 1.8% of exposed patients (49 of 2706)...Pulmonary AEs during therapy with ceritinib, alectinib, and lorlatinib occurred in 1.1%, 2.6%, and 1.8% of the patients, respectively...Lung toxicity is a rare albeit potentially severe side effect in NSCLC patients receiving ALK-TKIs, apparently more frequent with brigatinib. Its early recognition and treatment are crucial for the best outcome of this subgroup of patients, whose overall prognosis is being improved by the availability of several targeted agents.
- |||||||||| Biomarker, Review, Journal, PD(L)-1 Biomarker, IO Biomarker: Progress in the Management of Advanced Thoracic Malignancies in 2017. (Pubmed Central) - Apr 7, 2019
For oncogene-addicted NSCLC, next-generation tyrosine kinase inhibitors (TKIs) (such as osimertinib or alectinib) have demonstrated increased response rates and progression-free survival compared with first-generation TKIs in patients with both EGFR-mutated and ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC...In conclusion, the field of thoracic oncology is on the verge of a breakthrough which will open up many promising new therapeutic options for physicians and patients. The characterization of predictive biomarkers of sensitivity or resistance to immunotherapy, and the identification of the optimal therapeutic combinations (for ICIs) and treatment sequence (for oncogene-addicted NSCLC) represent the toughest upcoming challenges in the domain of thoracic oncology.
- |||||||||| Tecentriq (atezolizumab) / Roche, Alecensa (alectinib) / Roche
Trial completion date, Trial primary completion date, Combination therapy, PD(L)-1 Biomarker, Metastases: A Phase 1b Study of Atezolizumab in Combination With Erlotinib or Alectinib in Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - Feb 25, 2019 P1b, N=52, Active, not recruiting, Trial primary completion date: Oct 2018 --> Oct 2019 Trial completion date: Jan 2019 --> Sep 2019 | Trial primary completion date: Dec 2018 --> Sep 2019
- |||||||||| Alecensa (alectinib) / Roche
Review, Journal: Alectinib for advanced-positive non-small-cell lung cancer. (Pubmed Central) - Feb 8, 2019 Alectinib appears to be effective and safe for use in patients with metastatic ALK-positive NSCLC, with demonstrated superiority over crizotinib in terms of PFS rates. Research to better define ALK inhibitor resistance mechanisms and alectinib's place in therapy is ongoing.
- |||||||||| Alunbrig (brigatinib) / Takeda
Journal: The brigatinib experience: a new generation of therapy for ALK-positive non-small-cell lung cancer. (Pubmed Central) - Nov 29, 2018 Brigatinib, a next-generation ALK inhibitor, shows promising activity in ALK-rearranged NSCLC that have previously received crizotinib with response rates in ALTA ranging from 42-50%, intracranial response 42-67% and median progression-free survival 9.2-12.9 months. Randomized Phase III trial, ALTA-1 L is investigating brigatinib in ALK inhibitor-naive patients.
- |||||||||| Trial completion date, Tumor mutational burden, PD(L)-1 Biomarker, Metastases: My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors (clinicaltrials.gov) - Oct 26, 2018
P2a, N=765, Recruiting, Recruiting --> Active, not recruiting Trial completion date: Aug 2020 --> Mar 2021
- |||||||||| Review, Journal: Directed Therapies in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer. (Pubmed Central) - Sep 16, 2018
Of considerable importance when considering such therapies is the ability of each to overcome mutations conferring acquired resistance, as well as penetrate the central nervous system (CNS), the most common site of metastasis and traditionally the most difficult to breach. Herein is a review of the efficacy, indications, and degree of CNS penetration for the ALK-targeting agents crizotinib, ceretinib, alectinib, brigatinib, and lorlatinib, as well as a summary of ongoing clinical trials comparing these drugs.
- |||||||||| Alecensa (alectinib) / Roche
Enrollment open: ALINA: A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer (clinicaltrials.gov) - Sep 14, 2018 P3, N=255, Recruiting, Herein is a review of the efficacy, indications, and degree of CNS penetration for the ALK-targeting agents crizotinib, ceretinib, alectinib, brigatinib, and lorlatinib, as well as a summary of ongoing clinical trials comparing these drugs. Not yet recruiting --> Recruiting
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