H2AK119ub
H2AK119ub t1_j28unic wrote
Reply to Top state officials, including governor, set to receive a 20 percent pay hike, the largest in years by SomethingDrastic
Politicians vote to raise their own salaries. More news at 10.
H2AK119ub t1_j28uiab wrote
Reply to comment by spedmunki in Sighted this Dunkin's in Luzern, Switzerland. A single donut was $4. by toastyghostie
The COL in Switzerland is ridiculous - especially in the populous cities (Zurich, Lausanne, Basel, etc). The waiter is definitely not living in the nice parts on their own salary...lol.
H2AK119ub t1_j28ucxq wrote
Reply to comment by Smashed_Broccoli in New coronavirus subvariant, XBB, now widespread in New England by uxd
Probably not with inflation still hovering over >5%.
H2AK119ub t1_iy1lttc wrote
Reply to comment by jamesland7 in Was your energy bill really high this summer? Mine was - because I was an idiot during the BCCE opt in period and chose the wrong energy supplier. by flackboxessanta
The constant letters in mail are irritating.
H2AK119ub t1_ixzqlu4 wrote
Reply to comment by twnbay76 in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
You probably have some blocker or no journal access to JAMA. It works fine for me.
H2AK119ub t1_ixwt3px wrote
Reply to comment by virtuesdeparture in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
> Chemo for different cancers is going to be different too. My dad died of GBM 2.5 years ago, just a year after diagnosis. He was a personal trainer, in better shape than anyone I know, when he was diagnosed at 58 years old. 6 months later, he was a shell of himself and barely tolerating chemo. I’ve been watching dcvax since he was diagnosed, hoping they’d fast track fda approval and he could get it. > >
Big hugs. Sorry for your loss.
H2AK119ub t1_ixwsmu6 wrote
Reply to comment by BaLahKie in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
LOL. The FDA will approve the drug if they believe it provides a meaningful clinical benefit to patients. That's all that matters.
H2AK119ub t1_ixwrw26 wrote
Reply to comment by BaLahKie in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
Your control arm in a clinical trial can be placebo, standard of care (SOC), watch and wait, or a combination. The FDA has approved first in class medicines in high unmet need populations using ph1, single arm, non-randomized/blinded trials; they have stated recently they will probably do this no longer which is causing a big stir in pharma/biotech space. The DCVAX trial was plagued by many issues. Pseudo-progression of patients being a major one. They had to change the efficacy readout from PFS (time to disease progression) to OS (death) because they could not accurately readout from MRI's if people were getting better due to pseudo-progression. This is probably why the trial was so long.
H2AK119ub t1_ixwrb6q wrote
Reply to comment by bilyl in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
Not sure why you've focused on (mostly) old drugs and kinase inhibitors (known to be very dirty). Vemurafenib (BRAFi) is indicated and used in melanoma not NSCLC (another first for FBDD), Crizotinib (ALKi) is focused on ALK fusions, Trodelvy is a first in class ADC, Trastuzumab makes billions annually and is SOC in HER2+ breast cancer, and cetuximab is an old EGFR mAb that has been mostly supplanted by anti-VEGF mAb's in CRC (with FOLFOX chemo).
H2AK119ub t1_ixwptan wrote
Reply to comment by [deleted] in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
This is not how a clinical trial works at all. Nor is it how SOC treatment works for primary disease. Doctors (ie, oncologists) don't just try "random" treatment options.
H2AK119ub t1_ixw1tnd wrote
Reply to comment by bilyl in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
Can you name an example of this "one month life extension" drug in oncology?
H2AK119ub t1_ixvvqe3 wrote
Reply to comment by Pinky-and-da-Brain in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
This is not a new thought...the field of Immuno-Oncology has been around for decades.
H2AK119ub t1_ixvvblk wrote
Reply to comment by itwasquiteawhileago in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
Your latter point is probably why this trial took such a long time to accrue patients. Also, the difference between the treatment and external control in primary disease is 3 months for OS. IME - watch and wait is used for low grade disease.
H2AK119ub t1_ixvuxi7 wrote
Reply to comment by bilyl in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
The effect on OS for primary disease from point of randomization is 3 months (compared to the external controls). The FDA will need to decide if that is clinically meaningful.
H2AK119ub t1_ixvn8f6 wrote
Reply to comment by Z-Chomosome in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
You need exquisite controls when looking at historical data. Modern medicine has advanced incredibly in the past 20 years with technology and that can significantly blur the data.
H2AK119ub t1_ixv2z62 wrote
Reply to comment by Chemical-Hot in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03).
H2AK119ub t1_ixv0sac wrote
Reply to comment by klipseracer in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
It's effectively a single arm, uncontrolled trial; all patients involved in the "placebo" eventually cross over to the treatment arm. The investigators of the trial state that extracting DC's from GBM patients with poor prognosis is unethical without providing treatment.
H2AK119ub t1_ixuy1j6 wrote
Reply to comment by throwawayagain31 in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
I don't really understand your points. Current IO therapies don't work in GBM because it is a very heterogenous tumor type (not clonal like heme is) and there are few T cells in the brain for the MOA of checkpoint inhibitors to work. TAM reeducation is the closest a generic, non-personalized IO therapy could have for a decent shot on goal in this indication.
H2AK119ub t1_ixuv0h5 wrote
Reply to comment by throwawayagain31 in Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial by Sorin61
IO therapies have all bombed in GBM. GBM tumors are distinct to other cancer settings where IO has succeeded - eg., heme (ie, CAR-T) & inflamed tumors (anti-PD(L)1 mAbs). This one is interesting in that it uses the heterogeneity of the tumor itself (tumor lysate) to "educate" the immune cells (DC's).
H2AK119ub t1_ixuum3x wrote
An interesting study and a long running one (this study started in 2007 and finished recruiting in 2017). "Educating" dendritic cells with tumor lysate to give them "memory" to go and attack tumor cells. I'm not a fan of the controls (historical, external) or the study design (cross over) that were used in the trial but you can make a strong case that a placebo arm is unethical in GBM or any recurrent high grade tumor. Data are promising; this could be the first treatment to be added to frontline care in high grade gliomas after nearly two decades of failed trials.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847
H2AK119ub t1_ixtf8wi wrote
Reply to Startups in Boston? by massahoochie
Linkedin.
H2AK119ub t1_ixq77cy wrote
Reply to comment by mpjjpm in Why does the bathroom at the starmarket in td garden blue by EnvironmentalCable69
I am always curious as to what the conversion rate is at safe injection sites to rehab/treatment. I would bet low single digits.
H2AK119ub t1_ivwdl78 wrote
Reply to comment by Alfond378 in 'Second-class citizens': Boston officials fire back after Walgreens abruptly closes 3 stores by Omphaloskeptique
Nubian Station Walgreens was always desolate with half empty shelves. Literally no revenue or customer base for this location aside from the zombies.
H2AK119ub t1_iueup81 wrote
Reply to comment by crm115 in Mass. Tax Refunds Will Start To Flow On Tuesday by husky5050
You calculate the 13% based off the 5% of your income the state took. It's a really trivial amount of money for most folks (<$1000).
H2AK119ub t1_j29eatd wrote
Reply to comment by SgtPapa in New coronavirus subvariant, XBB, now widespread in New England by uxd
Inflation is a multi-factorial problem. Constrained supply and high demand is probably a major contributing factory though.