- |||||||||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Review, Journal: Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer. (Pubmed Central) - Dec 22, 2019 Ongoing clinical trials, evaluating crizotinib and alectinib as adjuvant treatments, will gauge the real impact of TKIs in terms of patients' disease free survival (DFS) and OS; other peri-operative investigations (e.g., neo-adjuvant strategies) will add information about ALK inhibitors' tumor growth restraint capacities and early adaptation mechanisms to ALK targeting. Nevertheless, multiple questions are and will remain unanswered: if should be treated indifferently all ALK+ patients or, alternatively, should be stratified in different risk groups based on the detectable residual disease [i.e., minimal residual disease (MRD) after surgery]; whether ALK inhibitors administration could facilitate the accumulations of persister cells driving resistance mechanisms to targeted therapies; if alternative strategies, as combined treatments targeting different molecular hubs, could enhance disease control and cancer eradication.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Review, Journal: RET fusions in solid tumors. (Pubmed Central) - Dec 19, 2019 Selective RET inhibitor drugs LOXO-292 (selpercatinib) and BLU-667 (pralsetinib) are also undergoing phase I/II and I clinical trials, respectively, with preliminary results demonstrating partial response and low incidence of serious adverse events. RET fusions provide a viable therapeutic target for oncologic treatment, and further study is warranted into the prevalence and pathogenesis of RET fusions as well as development of current and new tyrosine kinase inhibitors.
- |||||||||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Clinical, Journal: An autopsy case of anaplastic lymphoma kinase-positive lung cancer exacerbated in a short period of time: a case report. (Pubmed Central) - Nov 27, 2019 We report a case of a woman with metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer who was unable to swallow and was successfully treated with an oil-based alectinib liquid suspension. In cases of anaplastic lymphoma kinase-positive lung cancer poorly responsive to anaplastic lymphoma kinase inhibitors, re-examination of the tissue should be considered because there is a possibility of anaplastic lymphoma kinase-positive adenosquamous carcinoma.
- |||||||||| Alunbrig (brigatinib) / Takeda
Journal: An evaluation of brigatinib as a promising treatment option for non-small cell lung cancer. (Pubmed Central) - Nov 27, 2019 Besides this TKI, the second-line ALK inhibitors alectinib and ceritinib, as well as the third-line lorlatinib are approved for the treatment of ALK-positive NSCLC patients. The main challenge is to find sequences and combinations of ALK inhibitors which provide the best benefit for the patients.
- |||||||||| warfarin / Generic Mfg.
Journal: Effects of Seven Tyrosine Kinase Inhibitors on the Anticoagulation Activity of Warfarin (Pubmed Central) - Nov 27, 2019 Several studies have reported increased anticoagulation effect of warfarin(WF)when combined with tyrosine kinase inhibitors(TKIs), such as gefitinib and erlotinib...Seven different TKIs(afatinib, alectinib, axitinib, crizotinib, pazopanib, regorafenib, and vandetanib)were prescribed during treatment with WF of venous thromboembolism in 10 cancer patients...As all patients receiving WF with the 7 TKIs showed PT-INR elevation, enhancement of the anticoagulation effect of WF in the presence of TKIs appears to be highly frequent. PT-INR should be carefully monitored, and adjusting the WF dosage may become necessary during the WF and TKI combination therapy.
- |||||||||| Avastin (bevacizumab) / Roche, paclitaxel / Generic Mfg.
Clinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Advanced Non-Small Cell Lung Cancer: Sequencing Agents in the EGFR-Mutated/ALK-Rearranged Populations. (Pubmed Central) - Nov 19, 2019 Osimertinib has largely displaced first- and second-generation EGFR TKIs, including gefitinib, erlotinib, and afatinib, in the management of EGFR-mutated NSCLC...Dacomitinib has the distinction of being the first EGFR TKI to demonstrate a survival advantage compared with older TKIs...Alectinib and brigatinib, very specific ALK inhibitors, have proven superior to the erstwhile standard crizotinib in treatment-naive ALK+ NSCLC; PFS now routinely exceeds 2 to 3 years...Standard regimens include pemetrexed and carboplatin, as well as the E4599 regimen, combination solvent-based paclitaxel, carboplatin, and bevacizumab...However, in a subanalysis of patients with ALK and EGFR mutations enrolled in IMpower150, the addition of atezolizumab to the E4599 regimen led to a major overall survival benefit (hazard ratio < 0.40). In the absence of systemic chemotherapy, combining checkpoint inhibitors with TKIs in this setting remains investigational; several studies have demonstrated untoward pulmonary and hepatic toxicity.
- |||||||||| 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) - Nov 15, 2019 P1b, N=52, Active, not recruiting, In the absence of systemic chemotherapy, combining checkpoint inhibitors with TKIs in this setting remains investigational; several studies have demonstrated untoward pulmonary and hepatic toxicity. Trial completion date: Sep 2019 --> Dec 2019 | Trial primary completion date: Sep 2019 --> Dec 2019
- |||||||||| Trial primary completion date, Tumor mutational burden, IO Companion diagnostic, PD(L)-1 Biomarker, PD(L)-1 companion diagnostic, Metastases: BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - Nov 10, 2019
P2/3, N=580, Recruiting, No significant differences in discontinuation rate were found for alectinib, ceritinib, crizotinib, and chemotherapy. Trial primary completion date: Feb 2020 --> Jun 2019
- |||||||||| Alecensa (alectinib) / Roche
PK/PD data, Journal: Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib. (Pubmed Central) - Nov 2, 2019 P1 Unbound concentrations for alectinib and M4 did not appear substantially different between hepatic-impaired and healthy subjects. Moderate hepatic impairment had only a modest, not clinically significant effect on alectinib exposure, while the higher exposure observed in severe hepatic impairment supports a dose adjustment in this population.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca, Alecensa (alectinib) / Roche
Clinical, Journal: Targeted Therapy for Patients With Metastatic Non-Small Cell Lung Cancer. (Pubmed Central) - Oct 24, 2019 Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences.
- |||||||||| Alecensa (alectinib) / Roche
DO DOCTORS GET SICK? A CASE OF PSEUDOMESOTHELIOMATOUS CARCINOMA IN A 47-YEAR-OLD MALE NONSMOKER DOCTOR (Ernest N. Morial Convention Center - Exhibit Hall - Poster Area 2) - Oct 23, 2019 - Abstract #CHEST2019CHEST_4717; The treatment method for pseudomesotheliomatous tumors depends on the type and the origin of the given tumors with no specific guidelines published up to now and a poor prognosis is reported in most reviews in the literature. Our pt was ALK positive and it remains to see his clinical course with alectinib.
- |||||||||| Clinical, Review, Journal: ALK inhibitors, resistance development, clinical trials. (Pubmed Central) - Oct 18, 2019
The inevitable emergence of resistance to alk-directed therapy is central to ongoing research and daily clinical practice for affected patients. In the present review, we highlight the current treatment landscape, the available and emerging clinical trials, and the evolving clinical decision-making in ALK-positive nsclc, with a focus on Canadian practice.
- |||||||||| Xalkori (crizotinib) / Pfizer, Tagrisso (osimertinib) / AstraZeneca, Alecensa (alectinib) / Roche
Biomarker, Review, Journal, PD(L)-1 Biomarker, IO Biomarker: Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer. (Pubmed Central) - Oct 18, 2019 The approval of crizotinib for ROS1 rearrangements now means that patients also must be tested for that mutation. The biomarker for checkpoint inhibitors continues to be PD-L1 by immunohistochemistry stain, but whether testing will be necessary for patient selection if chemotherapy combinations are implemented will be determined soon.
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