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- ||| Alecensa (alectinib) / Roche
we knew alectinib was superior in 2016 with J Alex And Alex was press released in April 2017 (Twitter) - Sep 20, 2020
- ||||| Future SOC in 1st-line ALK+ NSCLC #CROWN study: Lorlatinib v Crizotinib: - PFS benefit 18.3 v 14.8m, impressive intracranial PFS The challenge will be which agent to select 1st-line: Lorlatinib v Alectinib v Brigatinib. Tox& resistance alteratns will matter #myesmo @bensolomon1 (Twitter) - Sep 20, 2020
- ||| Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
FDA event: Enrollment in CROWN started May 2017. FDA approval for 1st line alectinib was in November 2017 and 1st line brigatinib was May 2020. (Twitter) - Sep 19, 2020
- || Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Great analysis, @Jbauml. Aside from real comparator in 2020 being alectinib & not crizotinib, IMO we need to consider *opportunity costs* lost by using lorlatinib up front & not having it available as 2L-3L. Best drug up front? Maybe, but sequential may be better here. No data. (Twitter) - Sep 19, 2020
- || Alecensa (alectinib) / Roche
Remember those days..... this is why Alectinib remains an acceptable SOC. No BIRC in Alex. If lorla medians > 35m inv assessed then there’s a conversation to have. (Twitter) - Sep 19, 2020
- |||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Clinical: Going into this presentation, the AE profile was my concern based on prior use of lorlatinib. Patients are going to be on these drugs for a long time. Even minor toxicities are meaningful. Gr3/4 AE rate on lorlatinib is 72%, compared to 41% on alectinib and 61% on brigatinib (Twitter) - Sep 19, 2020
- ||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Predictably, there is no difference in OS with lorlatinib (just like there wasn't with alectinib or brigatinib) (Twitter) - Sep 19, 2020
- ||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Median is NE for lorlatinib with 18.3 months median FU. Median for alectinib was 25.7 months and 24 months for brigatinib. As a result, I think it is too early to say if that median is going to be better for lorlatinib - numbers get really small out at the 24 month mark #LCSM (Twitter) - Sep 19, 2020
- ||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Trying to compare apples to apples as much as I can, here is the BIRC PFS for brigatinib and PFS for alectinib (primary endpoint for that was not BIRC, but investigator assessed PFS). HR is clearly better for lorlatinib, but what about medians? (Twitter) - Sep 19, 2020
- |||||| Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
Clinical, Liquid Biopsy: #ESMO2020 #BFAST #CROWN #clinicaltrials #liquidbiopsy found G1202R upon Alectinib progression, 100mg Lorlatinib 2 1/2 years, progression free, QOL 🚜✔ @FoundationATCG @pfizer @christine_lovly @bensolomon1 #grateful (Twitter) - Sep 19, 2020
- ||| Alecensa (alectinib) / Roche
Clinical: The field moves so quickly. The ALEX study had not even been presented let alone Alectinib approved for first line when CROWN was initiated. (Twitter) - Sep 19, 2020
- || Alecensa (alectinib) / Roche
The writing however was on the wall. I started Alectinib in October 2016. Before crown even opened. (Twitter) - Sep 19, 2020
- ||| Alecensa (alectinib) / Roche
Clinical: CROWN opened to enrollment about 9 months before alectinib was approved in the 1L setting. As a global study, alectinib wouldn’t be available at all sites for much longer. And the initial designs of CROWN go back even further. (Twitter) - Sep 19, 2020
- |||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Clinical: Brain penetration is very important issue. However, crizotinib hasn't been standard of care first line for years. Why wasn't Alectinib used? #lcsm @alk_fusion (Twitter) - Sep 19, 2020
- || Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
It is important to know Lorla's PFS2, and perhaps make comparisons when available with alectinib and brigatinib on 1st line. Estimating a median OS ~5-9y what is the best sequence in the absence of 4th gen inhibitors is a big question. (Twitter) - Sep 19, 2020
- || Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Once a formal 1L option lorlatinib would be my go to unless it creates a copay issue (vs alectinib or brigatinib) If neurotox an issue I would switch over. That said hard to argue with this impressive data. We are in the Renaissance era of fusion-targeting TKIs and lorlatinib (Twitter) - Sep 19, 2020
- |||| Alecensa (alectinib) / Roche
Head-to-Head: It is impressive definitely, although 12 month PFS in ALEX was also >70% with alectinib, the HR is certainly better than the second gen TKI trials (yes criz arm did worse but can't compare that across trials, that's what the HR is for!) #ESMO20 #LCSM Need head to head trial(s)? (Twitter) - Sep 19, 2020
- |||| #ESMO20 Discussion of CROWN led by @christine_lovly. Markedly positive results from the study. Limitations aside, lorlatinib compares very favorably to other 2G TKIs - alectinib, brigatinib, ensartinib. Toxicity is different. (Twitter) - Sep 19, 2020
- |||| Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
Clinical: #ESMO20 #LCSM Question by @peters_solange to @bensolomon1 and @christine_lovly for the best clinical approach in 1L setting: 1) alectinib followed by Lorlatinib 2) Lorlatinib AEs are a real concern and the sequence is more appealing looking forward (Twitter) - Sep 19, 2020
- || Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Same story, comparing with the old crizotinib. Lorlatinib also has a different set of toxicities compare to Alectinib. (Twitter) - Sep 19, 2020
- ||| Alecensa (alectinib) / Roche
Head-to-Head: Very nice data. It will be, but always will be nice to have a head to head with Alectinib, the current standard of care. Sequential strategies it’s still a problem with the new generation TKI. (Twitter) - Sep 19, 2020
- |||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Clinical, Adverse events: #ESMO20, CROWN study lorlatinib vs crizotinib in 1L ALK+ #lcsm. Great data: PFS HR 0.28 in ITT and 0.2 in brain mets patients; but 1) side effects are not trivial (mood disorders & cognitive effects ) and 2) alectinib is another robust option with better tolerability ?. (Twitter) - Sep 19, 2020
- |||| Wow. PFS by BICR HR 0.28 substantially better (across trials) than we saw with alectinib or brigatinib (0.47-0.49). 12 month PFS rate 78% with lorlatinib vs 39% with crizotinib. #LCSM #ESMO20 @OncoAlert (Twitter) - Sep 19, 2020
- |||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Head-to-Head: Impressive results of the crown 👑 trial presented by @bensolomon1 , lorlatinib show a dramatic PFS impact at the interim analysis compared with crizotinib. We would love to have a head to head with Alectinib though. @alk_fusion @ALKLungCancer @OncoAlert #ESMO2020 @myESMO @IASLC (Twitter) - Sep 19, 2020
- ||| Alecensa (alectinib) / Roche
Preclinical: I agree. Alectinib retains its crown for now. Also need to know more about differences in acquired resistance pathways for these ALKi’s when given 1 st line. (Twitter) - Sep 19, 2020
- ||| Alecensa (alectinib) / Roche
Clinical, Real-World Evidence: Alectinib has raised the bar quite high. To justify new SOC I want to see great efficacy, great tolerance .Sequencing might be a further aspect to consider perhaps here though. Even for that we need real world data and longer follow up imho (Twitter) - Sep 19, 2020
- || Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
HR PFS for alectinib and brigatinib ~0.45 which was impressive against criz, itself a solid drug. Lorlatinib at 0.21 is amazing. Lipids not diff to tx (statin), neurotox vexing.Look forward to seeing talk @bensolomon1 but this looks like a hat trick in the champions league final (Twitter) - Sep 19, 2020
- || Alunbrig (brigatinib) / Takeda
Clinical, Journal: Intracranial remission with brigatinib rechallenge as fifth-line ALK inhibition therapy in a lung cancer patient. (Pubmed Central) - Sep 19, 2020
In 2012, ALK-directed targeted therapy became available, and crizotinib was administered...Brigatinib induced partial remission and was followed by lorlatinib and, later on, alectinib, when new metastases arose in the spinal cord and brain...All of the central nervous system relapses were symptomatic, with symptoms resolved rapidly during treatment. This case of a patient with EML4-ALK-rearranged non-small-cell lung cancer shows that sequential treatment with next-generation ALK tyrosine kinase inhibitors, including rechallenge, can induce profound remission even in heavily pretreated patients, especially if the central nervous system is the site of progression.
- || Alecensa (alectinib) / Roche
Yet pfs much lower than alectinib at fruition so not that exciting; criz always 10-11 months poor drug (Twitter) - Sep 19, 2020
- ||| Alecensa (alectinib) / Roche
Clinical: Maybe you can surprise us all by showing us the randomized comparison with the alectinib group 😉. Good luck tomorrow!! This will rocking all over the planet 👑! (Twitter) - Sep 18, 2020
- || Alecensa (alectinib) / Roche
Will eagerly wait to see the detailed results and want to know if it will become another SOC in 1st line therapy; especially whether it can replace Alectinib (Twitter) - Sep 18, 2020
- ||| Alecensa (alectinib) / Roche
Clinical: Agree with you. Loss of second line option is also important consideration. The data for brig and alectinib post 2nd gen TKI is pretty limited. (Twitter) - Sep 16, 2020
- || Lorbrena (lorlatinib) / Pfizer
Clinical, Journal: Pharmacological and clinical properties of lorlatinib in the treatment of ALK-rearranged advanced non-small cell lung cancer. (Pubmed Central) - Sep 16, 2020
These include hypocholesteremia, hypertriglyceridemia, edema, cognitive effects, weight gain, and diarrhea. Loratinib will play an increasing role in the management of ALK-rearranged NSCLC with the optimal sequencing of ALKi undergoing further research.
- || Alecensa (alectinib) / Roche
Ain’t this more Crizo specific? Any data on Alectinib? Keep seeing low grade transaminitis with Alectinib anyways (Twitter) - Sep 16, 2020
- | Alecensa (alectinib) / Roche
Trial completion date, Trial primary completion date: Anaplastic Lymphoma Kinase (ALK)-Positive Non-small Cell Lung Cancer (NSCLC) Post-alectinib Treatment Patterns (clinicaltrials.gov) - Sep 15, 2020
P=N/A, N=1, Active, not recruiting, Sponsor: Pfizer
Loratinib will play an increasing role in the management of ALK-rearranged NSCLC with the optimal sequencing of ALKi undergoing further research. Trial completion date: Jul 2020 --> Dec 2020 | Trial primary completion date: Jul 2020 --> Dec 2020
- | New P2 trial, Tumor mutational burden, PD(L)-1 Biomarker: CRAFT: The NCT-PMO-1602 Phase II Trial (clinicaltrials.gov) - Sep 15, 2020
P2, N=175, Not yet recruiting, Sponsor: German Cancer Research Center
- || Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
I agree. Alectinib has the best AE profile and is my goto 1L ALKi. Feel lorlatinib perhaps has slightly better CNS activity but will have to see the data from CROWN to see if we will be swayed.. (Twitter) - Sep 15, 2020
- || Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
With the differential toxicity profile clearly favoring alectinib or brigatinib, I cannot foresee a PFS HR that would make me switch. If they showed an OS benefit (something neither alectinib or brigatinib have yet), that would be meaningful (Twitter) - Sep 15, 2020
- || Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
But this is very different than FLAURA. Alectinib and brigatinib already provide excellent CNS control, and have much more favorable AE profiles. (Twitter) - Sep 15, 2020
- ||| Lorbrena (lorlatinib) / Pfizer, Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
Clinical: Agree I think ADAURA (adjuvant osi) CNS data is another piece to a high impact but still evolving story. CROWN (1L lorlatinib) is interesting but a crowded space already with alectinib and brigatinib, but a substantial improvement could reshape 1L (neurotox data also key here) (Twitter) - Sep 15, 2020
- | Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
Journal: Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity. (Pubmed Central) - Sep 13, 2020
ALK resistance mutations increase with each successive generation of ALK TKI and may be underestimated by tumor genotyping. Sequential treatment with increasingly potent ALK TKIs may promote acquisition of ALK resistance mutations leading to treatment-refractory compound ALK mutations.
- Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
[VIRTUAL] Indirect comparison between brigatinib and alectinib for the first-line treatment of ALK-positive non-small cell lung cancer (Abstract video presentations) - Sep 3, 2020 - Abstract #DGHO2020DGHO_2066;
These new agents have demonstrated to be efficacious in extending progression-free survival and are considered at least as safe than crizotinib, the first-in-class ALK inhibitor. Brigatinib and alectinib showed comparable efficacy, safety and HRQoL in treatment of patients with ALK-positive NSCLC.
- Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
[VIRTUAL] Indirect comparison between brigatinib and alectinib for the first-line treatment of ALK-positive non-small cell lung cancer (Abstract video presentations) - Sep 3, 2020 - Abstract #DGHO2020DGHO_1362;
These new agents have demonstrated to be efficacious in extending progression-free survival and are considered at least as safe than crizotinib, the first-in-class ALK inhibitor. Brigatinib and alectinib showed comparable efficacy, safety and HRQoL in treatment of patients with ALK-positive NSCLC.
- Alunbrig (brigatinib) / Takeda, Alecensa (alectinib) / Roche
[VIRTUAL] Indirect comparison between brigatinib and alectinib for the first-line treatment of ALK-positive non-small cell lung cancer (Abstract video presentations) - Sep 3, 2020 - Abstract #DGHO2020DGHO_603;
These new agents have demonstrated to be efficacious in extending progression-free survival and are considered at least as safe than crizotinib, the first-in-class ALK inhibitor. Brigatinib and alectinib showed comparable efficacy, safety and HRQoL in treatment of patients with ALK-positive NSCLC.
- ||| Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Clinical, P3 data, Journal: Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. (Pubmed Central) - Sep 2, 2020
Brigatinib and alectinib showed comparable efficacy, safety and HRQoL in treatment of patients with ALK-positive NSCLC. PRO data support the superior efficacy and tolerability of alectinib relative to crizotinib demonstrated in the ALEX study.
- | Alecensa (alectinib) / Roche
Journal, Tumor Mutational Burden: Brief Report: Rapid Acquisition of Alectinib Resistance in ALK-positive Lung Cancer with High Tumor Mutation Burden. (Pubmed Central) - Aug 27, 2020
High TMB and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.
- | Review, Journal: Diagnosis and Treatment of ALK Aberrations in Metastatic NSCLC. (Pubmed Central) - Aug 23, 2020
Several more expensive and time-consuming methods are also available nowadays which have the advantage to detect even rarer uncommon ALK fusion variants and mutations in tumour or blood samples. A review of the evolving testing-treatment landscape is needed to highlight the importance of properly diagnosing and treating this group of patients.
- || Clinical, Review, Journal: Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors. (Pubmed Central) - Aug 22, 2020
The ultimate acquisition of resistance to ALK-inhibitor therapy poses a challenge to ongoing research efforts, in addition to the routine management of these patients in the clinic. This review provides a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlights current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC.
- ||||| Alecensa (alectinib) / Roche
Clinical: #OncoAlert Case report by @MNagasaka in @OncologyAdvance describing a novel PLEKHH2-ALK fusion, in-frame, responded to alectinib. RNA-sequencing used here, helpful in detecting novel fusion partners. Reminder of the shortcomings of FISH for #ALK. #LCSM https://t.co/YEQ2iuSkIh (Twitter) - Aug 22, 2020