6 ms·
Trial results for new lung cancer drug are 'off the charts'
- hnpolicestate 2y agoStill no progress with small cell lung cancer? It killed my 43 year old aunt in less than two months back in 2002. Smoker though.
- dannykwells 2y agoDurva is starting to show some benefit here. https://www.cancernetwork.com/view/durvalumab-significantly-improves-survival-in-limited-stage-sclc https://www.cancernetwork.com/view/durvalumab-significantly-...
- adamredwoods 2y agoMy condolences, SCLC is rough. Sadly, it is different than large-cell, and the mutations are different. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038650/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038650/
- garrison 2y agoThere is https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer https://www.fda.gov/drugs/resources-information-approved-dru...
- zzzeek 2y agoWhy do all the new cancer drugs coming out end in the letter "B"?
- abracadaniel 2y agoI think the *mab ones are monoclonal antibodies, and the *nib ones are inhibitors. I don't think it's a hard rule though.
- andyjohnson0 2y agoIts a side-effect of the naming convention for generic drug naming [1]. Small molecule inhibitors end with “ib”. Monoclonal antibodies end with “mab”. Etc. [1] https://en.wikipedia.org/wiki/Drug_nomenclature https://en.wikipedia.org/wiki/Drug_nomenclature
- adamredwoods 2y agoTyrosine kinase, when mutated, causes uncontrolled cell growth. TKIs: Crizotinib (1st gen), alectinib. >> Lorlatinib is a third-generation, highly potent, macrocyclic ALK/ROS1 TKI that competitively binds to the adenosine triphosphate‐binding pocket, blocking ALK‐dependent oncogenic signaling. The advantage of Lorlatinib is high penetration of the blood-brain barrier by decreasing p‐glycoprotein‐1‐mediated efflux. Besides, it has broad‐spectrum activity against most known resistance mutations that develop during treatment with first and second‐generation ALK TKIs, including ALK G1202R mutation. The introduction of Lorlatinib to salvage these patients has shown the potential to add life. This has been shown in a global phase II study and other real-world studies, however, data is scant from LMIC. The most common toxicities were peripheral edema (9–48%), hyperlipidemia (47–94%), weight gain (3–25%), peripheral neuropathy (30%), fatigue (15–30%) and cognitive effect (6–18%) in earlier studies. The treatment discontinuation rate varied from 3–14% due to toxicity. https://www.nature.com/articles/s44276-024-00055-9 https://www.nature.com/articles/s44276-024-00055-9 https://en.wikipedia.org/wiki/Lorlatinib https://en.wikipedia.org/wiki/Lorlatinib https://en.wikipedia.org/wiki/Tyrosine_kinase https://en.wikipedia.org/wiki/Tyrosine_kinase
- JumpCrisscross 2y ago> advantage of Lorlatinib is high penetration of the blood-brain barrier Why is this essential to fighting lung cancer?
- ma2t 2y agoBrain is among the top sites where NSCLC tumors tend to metastasize https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251107 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251107
- JumpCrisscross 2y agoWow. Thanks. How do the cancer cells cross the blood-brain barrier?
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- dannykwells 2y agoNote that this drug is not new - it is fully approved for ALK+ NSCLC and has been since 2015. It's not clear why these data are just coming out now or what is different from the original trials run in this setting. https://en.wikipedia.org/wiki/Lorlatinib https://en.wikipedia.org/wiki/Lorlatinib
- westcort 2y agoNot mentioned in the article is the fact that lorlatinib, original studied in the phase 3 CROWN trial, was used in frontline management of advanced ALK-mutated non-small cell lung cancer (NSCLC) [0]. Five-year data indicate a significant progression-free survival benefit, with 60% of patients free of progression. Even after 60.2 months of follow-up, the median progression-free survival has not yet been reached [1]. It is the durability of progression-free survival that are most impressive and surprising here. That said, only 4% to 8% of patients with NSCLC will have ALK mutations/rearrangements, so while amazing, this finding is not applicable to all patients [2]. [0] https://www.nejm.org/doi/full/10.1056/NEJMoa2027187 https://www.nejm.org/doi/full/10.1056/NEJMoa2027187 [1] https://ascopubs.org/doi/10.1200/JCO.24.00581 https://ascopubs.org/doi/10.1200/JCO.24.00581 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597761/
- IG_Semmelweiss 2y agoCan you elaborate? In particular, this: >>>>Five-year data indicate a significant progression-free survival benefit, with 60% of patients free of progression. So far im with you. >>>>Even after 60.2 months of follow-up, the median progression-free survival has not yet been reached [1] This sounds awful? Or contradictory at best?
- ilya_m 2y ago>>>>Even after 60.2 months of follow-up, the median progression-free survival has not yet been reached [1] > This sounds awful? Or contradictory at best? No, quite amazing. At 5 years more than 50% of participants are progression-free. That's indeed off the charts for a metastatic lung cancer.
- benmarten 2y agoRCT? Doesn’t look like it…
- ilya_m 2y agoIt is: > In the phase 3 trial, 296 patients with advanced forms of non-small cell lung cancer were randomly assigned to receive either lorlatinib (149 patients) or crizotinib (147 patients, of whom 142 ultimately received treatment).
- nemo44x 2y agoToo bad cancer is the least of your concerns if you smoke. The COPD and numerous related illnesses are as bad if not worse. Hopefully this drug helps anyone with lung cancer.
- cschneid 2y agoThis particular lung cancer is a known, specific mutation and is unrelated to smoking. https://en.wikipedia.org/wiki/ALK_positive_lung_cancer#Epidemiology https://en.wikipedia.org/wiki/ALK_positive_lung_cancer#Epide...
- BenFranklin100 2y agoNot mentioned by the Guardian, but Lorlatinib was developed by Pfizer. https://www.nbcnews.com/health/cancer/lung-cancer-treatment-pfizers-lorbrena-extends-life-non-small-cell-lun-rcna154798 https://www.nbcnews.com/health/cancer/lung-cancer-treatment-...
- satellite2 2y agoIt specifies that the trial is funded by Pfizer, which kinds of give it away.
- BenFranklin100 2y agoWhy bury the lede? Pharma is doing well in helping transform lung cancer from a death sentence into a potentially survivable illness. https://www.wsj.com/health/healthcare/lung-cancer-treatment-deaths-5cfeb6fd?st=t7n9vudcvy2rmew&reflink=article_copyURL_share https://www.wsj.com/health/healthcare/lung-cancer-treatment-...
- noobermin 2y agoJust a comment, these drugs are very expensive. Especially as these aren't one time treatments but are taken daily, costing patients 1000s a month.
- Faaak 2y agoThankfully, in France they will be paid for by the state. Same in Switzerland
- crubier 2y agoNot really. If they’re expensive, in France the health system might decide to not pay for it. Or pay for it in very restricted cases. You wouldn’t know about it though, your doctors would just tell you that they are out of therapeutic options and to gather with your loved ones, unaware of the fact that your cancer is actually treatable. Source: Am French, happened to a very good friend of mine 5years ago. They ended up surviving after a gofundme paid for a US treatment, administered in a private hospital in Barcelona. They made it and are doing well now, thanks to the “evil US private capitalist health system”
- brianwawok 2y agoIt’s such a tough thing. To me my life is worth infinite money and every possible dollar I can get ahold of. If that applied to everyone then we go literally bankrupt and spend every available dollar of GDP very quickly.
- jseliger 2y agoTo me my life is worth infinite money I'm facing just this problem and my life is not worth "infinite money:" http://jakeseliger.com/2024/05/16/the-financial-costs-of-healthcare-costs-or-is-keeping-me-alive-worth-it http://jakeseliger.com/2024/05/16/the-financial-costs-of-hea...
- whimsicalism 2y agoOr just not paid for at all, as is common in EU countries (cancer survivability is much worse in the EU and if it weren’t for American obesity would push EU lifespans below the US) Zooming out - if the US were like France, these drugs would not be developed in the first place. France is lucky that there are other countries willing to shoulder R&D costs for them.
- dontreact 2y agoAnother good reason more people should get screened for lung cancer. If you can find it early, you can maybe halt the progression with this drug!
- mistercheph 2y ago[flagged]
- noncoml 2y agoLung cancer is not the death penalty that it use to be if you are “lucky” to have one of the mutations that this, and other similar drugs, target.
- cschneid 2y agoMy dad has survived ~10 years now with ALK lung cancer due to this family of drugs. It was surprise stage 4, with no warning. Had a 6 month prognosis, but instead he's still with us and doing really well.
- admissionsguy 2y agoAccording to a (very) quick google search: - the drug is for "ALK positive Non–small cell lung cancer (NSCLC)" - NSCLC is 85% of all lung cancers, of which 3% to 5% are ALK+. so it would appear to apply to at most 4% of all lung cancers. Are the numbers correct? Even so, huge deal for tens of thousands of people each year.
- odyssey7 2y ago“Lorlatinib and crizotinib are both ALK tyrosine kinase inhibitors (TKIs). ALK TKIs are targeted treatments that bind to the ALK protein found in ALK-positive non-small cell lung cancer and stop the growth of tumour cells.” Great, so this is a targeted approach that works 60% of the time (in the case of Lorlatinib) in one highly specific area of the highly diverse space of possible cancers, many of which have never been observed before and for which you could never enroll enough patients to have a robust clinical trial. How can this approach be generalized and scaled, meaning that for a given patient with a given cancer, you can run an algorithm and synthesize molecules that will work? In CS the paradigm involves knowing how to solve an unseen problem instance, not just remembering solutions to specific, well-studied problem instances.
- admissionsguy 2y ago> meaning that for a given patient with a given cancer, you can run an algorithm and synthesise molecules that will work? The paradigm is called rational drug design (+ personalised medicine) and its scope is quite limited at the current level of technology. To achieve what you describe, we need to solve all of the following: - a way to recognise the molecular mechanism of a particular cancer and identify potential drug targets - a way to characterise the targets - in the previous step you identified a protein, now you need to know its shape (X-ray crystallography (potentially years), AlphaFold). We need to know how the target should be modified to disrupt the disease. - a way to design a molecule that binds the target specifically and in the desired way - a way to synthesise the molecule quickly & efficiently - a way to predict the molecule's interactions at all stages of metabolism, taking into account the patient's individual phenotype (different people have significant variations in drug-digesting enzymes) Significant (decades at the current rate) progress in all of these areas is needed before this sort personalised medicine has a chance of becoming feasible.