Alnylam presents contemporary analysis of HELIOS-B Phase 3 study of vutrisiran
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Medscape
2 days ago
- Medscape
Tibremciclib for Advanced Breast Cancer: Is It Worth It?
Adding the novel CDK4/6 inhibitor tibremciclib (Betta Pharmaceuticals) to second-line fulvestrant significantly extended progression-free survival (PFS) in patients with HR-positive/HER2-negative advanced breast cancer, but with the tradeoff of increased toxicity, new data suggest. Compared with fulvestrant alone, the combination prolonged median PFS for these patients by 11 months, according to results from the phase 3 TIFFANY trial. However, similar to existing CDK4/6 inhibitors, the tibremciclib-fulvestrant combination added to treatment side effects — including substantially higher rates of diarrhea, hematologic toxicities, and hypokalemia. The authors of the analysis, published in JAMA Oncology , described the toxicities as "manageable," emphasizing that few patients stopped treatment because of them. Study author Xichun Hu, MD, of Fudan University Shanghai Cancer Center, told Medscape Medical News that tibremciclib compares favorably with other CDK4/6 inhibitors in terms of dose reduction and discontinuation rates. However, Hu noted, that's based on cross-trial comparisons, which have to be interpreted with caution. Kathy Miller, MD, who was not involved in the trial, had a similar take. 'Toxicity actually looks similar to ribociclib and palbociclib, with primarily myelosuppression and little non-heme toxicity,' Miller, of the Melvin and Bren Simon Comprehensive Cancer Center at Indiana University, told Medscape Medical News. Tibremciclib plus fulvestrant was recently approved in China for HR-positive/HER2-negative advanced breast cancer following results from the trial, but the combination has yet to be approved in the US. The Benefits vs the Risks In the trial, Hu and colleagues studied the safety and efficacy of the new agent among patients from 69 centers in China who had experienced progression while on endocrine therapy and had received no more than one line of chemotherapy. A total of 274 patients were randomized (2:1) to receive either tibremciclib (400 mg orally, once daily) or placebo plus fulvestrant until disease progression, death, or treatment discontinuation over a median follow-up of 13 months. Eighty patients (43.5%) in the tibremciclib arm and 64 (71.1%) in the placebo arm experienced a PFS event (disease progression or death). Tibremciclib plus fulvestrant significantly improved PFS to 16.5 months versus 5.6 months with fulvestrant alone, reducing the risk of progression by 63% (hazard ratio [HR], 0.37; P < .001). As for safety, adverse events were higher in the treatment arm. The most common treatment-emergent adverse events were diarrhea (79.3% in the tibremciclib arm vs 13.3% in placebo arm), neutropenia (75.5% vs 15.6%), leukopenia (73.9% vs 16.7%), and anemia (69% vs 21.1%). Nausea and vomiting were also more common with tibremciclib, at 37% and 40.2%, respectively — versus 18.9% and 11.1% in the placebo group. Most often, those adverse events were grade 1 or 2. However, 50.5% of patients in the tibremciclib group had a grade 3 or higher treatment-emergent adverse event, versus 21.1% in the placebo group. The most common were neutropenia (15.2% vs 5.6%), anemia (12.0% vs 4.4%), and hypokalemia (12% vs 0%). Hypokalemia was often due to diarrhea and was managed with electrolyte monitoring and potassium supplementation, Hu said. One-third of patients in the tibremciclib arm developed hypertriglyceridemia (5.4% grade 3 or higher) — a rate higher than that seen with other CDK4/6 inhibitors. Cases were managed with lipid-lowering agents such as atorvastatin. More patients on tibremciclib experienced dosing interruptions due to adverse events (54% vs 23%), and dose reductions were also more common with the combination therapy (18.5% vs 4.4%). However, only four patients (all in the tibremciclib arm) discontinued treatment due to side effects. Overall, the adverse event profile of tibremciclib lines up with that of other CDK4/6 inhibitors and comes with better PFS, Hu said, noting that "the benefit-risk balance of tibremciclib plus fulvestrant appears highly favorable." In TIFFANY, the authors note d that cases of neutropenia and leukopenia were numerically lower than in trials of abemaciclib, dalpiciclib, and palbociclib plus fulvestrant. According to Hu, tibremciclib is structurally different from other drugs in its class, with a greater selectivity for CDK4 and less inhibition of CDK6 and CDK9, which may reduce the incidence of neutropenia as well as severe diarrhea. Plus, the PFS improvement seen in TIFFANY was greater, Hu said. Pa lbociclib in PALOMA-3 showed a median PFS of 9.5 months vs 4.6 months for fulvestrant alone (HR, 0.46); abemaciclib in MONARCH led to a PFS of 11.5 months vs 5.6 months (HR, 0.38, a Chinese population); and dalpiciclib in DAWNA-1 achieved 16.6 months vs 7.2 months (HR, 0.50, also in Chinese patients). While these are cross-trial comparisons, it's still unclear exactly how tibremciclib stacks up against other drugs in its class (including its impact on overall survival). The authors also caution that, because the trial exclusively enrolled Chinese patients without prior CDK4/6 inhibitor exposure, the findings may not be generalizable to broader populations, particularly in regions like North America and Europe. Miller pointed to the generalizability question as well, noting that fulvestrant monotherapy is typically not the standard of care in the US and other Western countries. 'This [study] joins a long list of second-line endocrine studies that show drug activity but don't compare to standard of care and don't really tell us how to best use the drug,' Miller said.
Yahoo
2 days ago
- Yahoo
This 'marvellous' Oral-B electric toothbrush is half off on Amazon — plus 5 more really good deals up to 75% off
More than 1,000 Amazon shoppers bought this popular Oral-B Pro Limited Rechargeable Electric Toothbrush in the past month. Studies have shown that poor dental care can increase our chances of developing bacterial infections in the bloodstream, while gum disease increases our risk of developing heart disease. On the flip side, good oral health can lessen one's risk of developing diabetes, cancer and chronic respiratory diseases — all the more reason to take your dental care seriously. For those looking to invest in their smile, this Amazon Canada deal is worth checking out. Right now, shoppers can save 50 per cent on an Oral-B Pro Limited Rechargeable Electric Toothbrush. To learn more and discover why more than 1,000 Amazon shoppers have purchased this "game-changer" toothbrush in the past month, check out the details below. The details Oral-B's Pro Limited rechargeable toothbrush removes 300 per cent more plaque along the gum line than a regular manual toothbrush, leaving you with a superior, post-dentist clean. The high-tech toothbrush has a built-in timer that pulses every 30 seconds to indicate when to switch areas of your mouth. Its pressure sensor alerts you when brushing too hard, and its MicroPulse bristles reach deeper between teeth than a regular manual toothbrush. What people are saying 1,900+ Amazon reviews 4.4-star average rating More than 1,000 Amazon shoppers purchased in the past month It's a "game-changer," according to one enthusiastic reviewer, who reports their teenage son "loves it." The toothbrush "checks all of my boxes," writes another. Adding, it does a "marvellous job" at keeping their gums and teeth "healthy." $60 $120 at Amazon The "cool feature" about this toothbrush is that the head "twists/rotates," which provides a "pretty slick scrubbing action," says a third shopper. Overall, it's a "heck of an upgrade from manual brushing," they write. Despite its many positive reviews, some users report that the battery life "isn't bad" but "could be better." It starts to "slow down after 24 hours," according to one reviewer. The verdict If you're in the market for a new electric toothbrush or are considering switching from a manual, Oral-B's Pro Limited toothbrush might be for you. The dentist-approved design removes 300 per cent more plaque than a manual toothbrush and helps users refrain from over-brushing. However, some shoppers report its battery life could be better, something to keep in mind when comparing your options. 5 more really great Amazon deals
Yahoo
2 days ago
- Yahoo
Jim Cramer on Eli Lilly Stock: 'It Just Got Pole-Axed, Laid to Waste'
Eli Lilly and Company (NYSE:LLY) is one of the stocks Jim Cramer commented on. Cramer highlighted the reasons behind the stock's decline recently. He remarked: 'Last and least, I look at the drug stocks and I can't believe how awful they really are, with now Eli Lilly last joining the ugly fray with its less than impactful, less thought weight loss, the pill. The Street was hoping that Lilly would be able to replace its onerous GLP-1 injection with a simple pill that would produce an equal amount of weight loss. No such luck. The stock, it just got pole-axed, laid to waste.' Pixabay/Public Domain Eli Lilly and Company (NYSE:LLY) develops and markets pharmaceuticals for diabetes, obesity, cancer, autoimmune conditions, neurological disorders, and other diseases. The company's portfolio includes treatments across multiple therapeutic areas. In a July episode, Cramer mentioned the company and said: 'What I'm thinking, as someone who owns Eli Lilly for the Charitable Trust and who wishes I owned PepsiCo, is that there might be a short-term peak in the use of these drugs (GLP-1s). The Achilles heel of these drugs is that they're too effective. At some point, you lose enough weight, and you might think you can stop taking them… Whatever the case, if Eli Lilly is going to break out from this level, it needs breakthroughs in new areas, heart, brain, that it just doesn't have right now, or there has to be some new data that shows something else positive that the GLP-1 drugs can do. While we acknowledge the potential of LLY as an investment, we believe certain AI stocks offer greater upside potential and carry less downside risk. If you're looking for an extremely undervalued AI stock that also stands to benefit significantly from Trump-era tariffs and the onshoring trend, see our free report on the best short-term AI stock. READ NEXT: 30 Stocks That Should Double in 3 Years and 11 Hidden AI Stocks to Buy Right Now. Disclosure: None. This article is originally published at Insider Monkey. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
