Interval ratio – ATRX http://atrx.net/ Wed, 28 Sep 2022 13:52:31 +0000 en-US hourly 1 https://wordpress.org/?v=5.9.3 https://atrx.net/wp-content/uploads/2021/10/icon-3-120x120.png Interval ratio – ATRX http://atrx.net/ 32 32 Pyrotinib plus trastuzumab/docetaxel prolongs PFS in HER2+ metastatic breast cancer https://atrx.net/pyrotinib-plus-trastuzumab-docetaxel-prolongs-pfs-in-her2-metastatic-breast-cancer/ Wed, 28 Sep 2022 13:30:00 +0000 https://atrx.net/pyrotinib-plus-trastuzumab-docetaxel-prolongs-pfs-in-her2-metastatic-breast-cancer/ Adding pyrotinib to trastuzumab (Herceptin) and docetaxel significantly improved progression-free survival (PFS) compared to trastuzumab/docetaxel alone in patients with HER2-positive metastatic breast cancer, according to data from the phase 3 PHILA trial (NCT03863223).1 Data presented at the 2022 ESMO Congress showed that the median PFS was 24.3 months (95% CI, 19.1-33.0) as assessed by the […]]]>

Adding pyrotinib to trastuzumab (Herceptin) and docetaxel significantly improved progression-free survival (PFS) compared to trastuzumab/docetaxel alone in patients with HER2-positive metastatic breast cancer, according to data from the phase 3 PHILA trial (NCT03863223).1

Data presented at the 2022 ESMO Congress showed that the median PFS was 24.3 months (95% CI, 19.1-33.0) as assessed by the investigator with the pyrotinib regimen versus 10 .4 months (95% CI, 9.3-12.3) with trastuzumab plus docetaxel alone, resulting in a 59% reduction in risk of disease progression or death (RR, 0.41; 95% CI %, 0.32-0.53; P < .0001). The 12-month PFS rates in the investigational and control arms were 74.3% and 44.0%, respectively; at 24 months, these rates were 50.3% and 16.6% respectively.

“To our knowledge, this is the second Phase 3 trial to demonstrate that PFS benefits from dual HER2 inhibition in the first-line treatment of HER2-positive metastatic breast cancer,” said the lead author of the study, Binghe Xu, from the Department of Medical Oncology at Cancer Hospital. The Chinese Academy of Medical Sciences and Peking Union Medical College, and their colleagues, said during a presentation of the data.

The irreversible pan-HER inhibitor, pyrotinib, has previously demonstrated encouraging antitumor activity when combined with capecitabine in patients with HER2-positive metastatic breast cancer. More specifically, the data from the phase 3 PHOEBE trial (NCT03080805), showed that the doublet resulted in a median PFS of 12.5 months (95% CI, 9.7-NR) vs 6.8 months (95% CI, 5.4-8.1) with lapatinib (Tykerb) plus capecitabine (HR, 0.39; 95% CI, 0.27-0.56; P < .0001).2

The Phase 3, multicenter, double-blind, placebo-controlled PHILA trial enrolled patients with pathologically confirmed, treatment-naïve HER2-positive metastatic breast cancer. These patients were required to have measurable disease according to RECIST v1.1 criteria and an ECOG performance status of 0 or 1.

A total of 590 participants were randomized 1:1 to receive oral pyrotinib 400 mg daily (n=297) or placebo (n=293) plus intravenous (IV) trastuzumab 8 mg/kg during cycle 1 and 6 mg/kg in subsequent cycles and docetaxel IV at 75 mg/m2 on day 1 of each 21-day cycle. Treatment was continued until disease progression, intolerable toxicity, withdrawal of the patient or decision of the investigator.

Patients were stratified by history of neoadjuvant or adjuvant trastuzumab (yes vs. no) and hormone receptor status (estrogen receptor (ER) positive and/or progesterone receptor disease vs ER negative and ER negative disease. progesterone receptors).

The primary endpoint of the trial was PFS as assessed by the investigator. Primary secondary endpoints included PFS as assessed by independent review committee, overall survival, objective response rate (ORR), duration of response (DOR), clinical benefit rate, and security.

The data cut-off date for the pre-specified interim analysis was May 25, 2022. The median follow-up for pyrotinib treatment was 15.8 months (range, 0.4-36.2) and 14.9 months (range, 0.4-35.3) with trastuzumab plus docetaxel.

According to the IRC assessment, the median PFS with pyrotinib plus trastuzumab/docetaxel was 33.0 months (95% CI, 19.4 – not reached [NR]) vs 10.4 months with trastuzumab plus docetaxel alone, resulting in a 65% reduction in risk of disease progression or death (RR, 0.35; 95% CI, 0.27-0.46 ; P < .0001). The 12-month PFS rates were 77.3% and 44.5%, respectively; the 24-month rates were 55.3% and 13.3%, respectively.

Within the subset of patients who received prior (neo)adjuvant trastuzumab, those who received the pyrotinib regimen had a median PFS that has not yet been achieved (95% CI, 14.6-NR) vs 9.3 months (95% CI, 6.3-12.4) with trastuzumab/docetaxel (HR, 0.23; 95% CI, 0.12-0.46). In those who had not received prior (neo)adjuvant trastuzumab, the median PFS in the investigation and control arms was 21.9 months (95% CI, 16.5-30.5) and 10.4 months (95% CI, 9.5-12.4), respectively (HR, 0.45; 95% CI, 0.34-0.59).

Additionally, in those with a treatment-free interval with prior adjuvant therapy of at least 12 months and less than 24 months who received the pyrotinib regimen, the median PFS was not yet achieved (95% CI, 14.7-NR) vs 8.3 months (95% CI, 6.2-11.8) with trastuzumab plus docetaxel (HR, 0.22; 95% CI, 0.10-0.50). In those who had a treatment-free interval of at least 24 months and received either pyrotinib treatment or control treatment, the median PFS was 22.2 months (95% CI, 12.5-NR) and 13.0 months (95% CI, 10.3-16.6), respectively (HR, 0.57; 95% CI, 0.37-0.87).

Adding pyrotinib to trastuzumab and docetaxel resulted in an ORR of 82.8% (95% CI, 78.1% to 86.9%) per investigator assessment versus 70.6% (CI 95%, 65.1% to 75.8%) with trastuzumab plus docetaxel. Of those who responded to pyrotinib treatment, 6.4% achieved a complete response, 76.4% had a partial response, and 10.4% had stable disease; 2.7% of patients showed disease progression. The median DOR in the investigation and control arms was 25.9 months (95% CI, 17.3-NR) and 9.5 months (95% CI, 8.3-10.6) , respectively.

The safety profile of the pyrotinib regimen was manageable, and adverse events (AEs) were consistent with prior reports for each agent.

All patients experienced treatment-related AEs (TRAE) in the investigation group versus 99.7% of those in the control group; these effects were grade 3 or higher in 89.9% and 76.5% of patients, respectively. Severe EITRs occurred in 24.9% of people in the experimental group versus 6.1% of those in the control group.

EITRs led to interruption, reduction, and discontinuation of treatment in 56.6%, 25.9%, and 13.1%, respectively, of patients who received the pyrotinib regimen; these rates were 24.2%, 3.1%, and 7.2%, respectively, in those who received trastuzumab plus docetaxel. No patient in the investigation group died as a result of TRAE versus 1 patient in the control group.

The most common side effects were diarrhea, white blood cell count decreased, neutrophil count decreased, anemia, vomiting, weight loss, nausea, hypokalemia, blood glucose increased aspartate aminotransferase, increased alanine aminotransferase, alopecia, increased blood creatinine, asthenia, decreased appetite, hypoalbuminemia, hypertriglyceridemia and hypercholesterolemia.

References

  1. Xu B, Yan M, Ma F, et al. Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer (PHILA): a phase III randomized trial. Anne Oncol. 2022;33(supplement 7):S1387. doi:10.1016/j.announce.2022.08/014
  2. Xu B, Yan M, Ma F, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicenter, open-label, randomized, controlled phase 3 trial. Lancet Oncol. 2021;22(3):351-360. doi:10.1016/S1470-2045(20)30702-6
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GGT/HDL-c ratio linked to the development of diabetes | Latest news for doctors, nurses and pharmacists https://atrx.net/ggt-hdl-c-ratio-linked-to-the-development-of-diabetes-latest-news-for-doctors-nurses-and-pharmacists/ Sat, 24 Sep 2022 01:00:08 +0000 https://atrx.net/ggt-hdl-c-ratio-linked-to-the-development-of-diabetes-latest-news-for-doctors-nurses-and-pharmacists/ The ratio of gamma-glutamyl transferase (GGT) to high-density lipoprotein cholesterol (HDL-c) shares a positive, nonlinear relationship with incident diabetes, reports a recent Japanese study. The researchers conducted a retrospective cohort analysis of 15,171 patients (mean age 43.69 years, 53.75% male), in whom the GGT/HDL-c ratio was determined by blood test after an overnight young. Incident […]]]>

The ratio of gamma-glutamyl transferase (GGT) to high-density lipoprotein cholesterol (HDL-c) shares a positive, nonlinear relationship with incident diabetes, reports a recent Japanese study.

The researchers conducted a retrospective cohort analysis of 15,171 patients (mean age 43.69 years, 53.75% male), in whom the GGT/HDL-c ratio was determined by blood test after an overnight young. Incident diabetes was defined as blood glucose ≥ 7 mmol/L, glycated hemoglobin ≥ 6.5%, or self-reported diagnoses.

During a median follow-up of 64.9 months, 350 patients developed diabetes, an incidence rate of 3.77 per 1,000 person-years.

A multivariate analysis, fully adjusted for potential confounders, showed that each additional unit of GGT/HDL-c ratio resulted in a 1.3% increased risk of incident diabetes (relative risk [HR]1.013, 95% confidence interval [CI]1.002–1.024).

By applying a penalized spline method to the Cox proportional hazards regression model, the researchers also found that diabetes risk shared a nonlinear relationship with the log-transformed GGT/HDL-c ratio, with an inflection point at the ratio value 6.477.

HR estimates were 2.568 (95% CI, 1.157 to 5.699) and 1.012 (95% CI, 1.001 to 1.023) on the left and right sides of the inflection point, respectively.

“When the GGT/HDL-c ratio is less than 6.477, there is a significant positive association with the risk of diabetes. The result should provide a benchmark for clinical monitoring of the GGT/HDL-c ratio,” the researchers said.

“When the level of the GGT/HDL-c ratio is below the inflection point, lowering the level of the GGT/HDL-c ratio can significantly reduce the risk of developing diabetes in the future,” they added. .

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Adaptimmune Therapeutics: depressed despite upcoming BLA (NASDAQ: ADAP) https://atrx.net/adaptimmune-therapeutics-depressed-despite-upcoming-bla-nasdaq-adap/ Tue, 20 Sep 2022 08:19:00 +0000 https://atrx.net/adaptimmune-therapeutics-depressed-despite-upcoming-bla-nasdaq-adap/ Artur Plawgo/iStock via Getty Images I covered Adaptimmune Therapeutics (NASDAQ:ADAP) several times before. ADAP is a leader in TCR therapies that has seen better days and may see better days in the years to come. However, this year is not This year. With the success of SPEARHEAD, afami-cell may well become the first FDA-approved T […]]]>

Artur Plawgo/iStock via Getty Images

I covered Adaptimmune Therapeutics (NASDAQ:ADAP) several times before. ADAP is a leader in TCR therapies that has seen better days and may see better days in the years to come. However, this year is not This year.

With the success of SPEARHEAD, afami-cell may well become the first FDA-approved T cell therapy in a solid tumor indication. The main concern is durability. Afami-cell has shown an excellent response to treatment so far. They saw a response rate of 34%, well above the 18% threshold, so if the lower bound of the confidence interval can be higher than 18%, they have a high chance of success. The problem, as I said, is durability.

As I noted in the previous article:

Another one [positive] the angle with durability is Data of the SURPASS trial presented at the SITC last year. Data show that adding an AKT inhibitor (AKTi) when making afami-cel (ADP-A2M4) can reshape gene expression towards better proliferation or cytotoxicity, which may increase the durability of the response. These next-generation SPEAR-T cells have enhanced memory and higher proliferation when AKT signaling is inhibited during ex vivo T cell expansion, all within the controlled manufacturing process. Post-infusion analysis then showed that “ADP-A2M4CD8 SPEAR T cells made with AKTi demonstrated higher median persistence in peripheral blood of patients in the Phase 1 SURPASS trial, in peak vector copy number and in percentage of maximum recovery, compared to those made without.” Yes, all of this data needs to be translated into a full-scale clinical program, but the data presented dispels some of the sustainability concerns.

Updated data from this trial was announced just a few days ago. The data showed:

The study enrolled 44 patients in the US, Canada and EU who had received a median of 3 prior lines of treatment and yet had progressed to advanced metastatic cancers. They received a single dose of ADP-A2M4CD8, and 43 were evaluable for efficacy as of August 1.

Data from the ongoing trial indicate an overall response rate of 33%, including two cases of unconfirmed partial responses.

The median duration was 12 weeks and the disease control rate was 86%, while five patients had confirmed clinical responses, including one complete response.

A subset of 25 patients with ovarian, urothelia, and head and neck cancers demonstrated a 44% response rate.

Of the notable adverse events, 32 people (73%) had cytokine release syndrome (CRS), with the majority of events resolving and categorized as low grade (~86% ≤ Grade 2). However, there have been two deaths related to ADP-A2M4CD8.

Noting the unmet medical need for platinum-resistant cancer, ADAP points out that currently approved therapies lead to less than 13% overall response rates, less than four months median progression-free survival, and 13 months or less median overall survival.

However, the problem is that this is for future trials; the current trial does not have the SURPASS benefit, and the BLA that will be filed this year may have durability issues. However, as fierce biotech noted last year about this lawsuit:

Adaptimmune said 75% of responses are ongoing, with durations ranging from four to 65 weeks. Biotechnology considers the interim data “encouraging” and has not yet reached the median duration of response.

From their last company presentation, I see that the median duration of response or mDOR was 52 weeks. I also note that only 1 in 10 MRCLS patients actually had a treatment response in the pooled data of 69 patients with synovial sarcoma or MRCLS who received afami-cell in the phase 1 trial and cohort 1 of the SPEARHEAD-1 phase 2 trial. Response improved by 25% in the Phase 2 SPEARHEAD-1 trial.

Another concern with the BLA is the actual market. The indications are going to be synovial sarcoma and myxoid/round cell liposarcoma or MRCLS. Even together, these two markets are very small, and the actual earning potential is less than a hundred million dollars.

According to a The source:

The incidence of synovial sarcoma has been estimated at 2.75 per 100,000. The majority of cases involve the lower limbs. About 800 new cases occur in the United States each year, and this tumor accounts for about 5-10% of all soft tissue sarcomas.

According to another The source:

The incidence is approximately 1/769,000 per year and accounts for 30% or less of all LS cases.

So, taking the two together, there are no more than 1,000 patients in the US each year, and even with 10% penetration at launch, we’re only seeing 100 patients treated. Of course, being an orphan drug, afami-cell can be very expensive; however, even so, the market does not exceed $100 million. And that’s if you’re feeling optimistic. However, keep in mind that this will be the first modified T cell therapy to hit the market in a solid tumor indication. This is just the start of the game here for Adaptimmune, if all goes well. Only the first generation MAGE-A4 platform can have 40 times more targeted patients according to their latest business platform.

finance

ADAP has a market capitalization of $249 million and a cash reserve of $97.8 million. R&D expenses for the three and six months ended June 30, 2022 were $34.7 million and $71.5 million, respectively, while G&A expenses for the three and six months ended June 30, 2022 were of $14.6 million and $31.4 million respectively. This means that the company has no cash for more than 2 quarters from July. In light of this, the company launched a mixed $400 million offering in August.

At the end of the line

ADAP has a difficult cash position, despite plans to file a BLA this year. There are many reasons for this. One is the small market size of its immediate indications. The second concerns sustainability issues. The third is security; there have been two patient deaths in its trials so far, both related to the treatment. Taking all these elements into account, ADAP remains moderate despite being a leading company in the TCR. However, more clarity around the BLA could change all that.

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Second-hand smoke during the first trimester increases the risk of coronary artery disease in infants | Latest news for doctors, nurses and pharmacists https://atrx.net/second-hand-smoke-during-the-first-trimester-increases-the-risk-of-coronary-artery-disease-in-infants-latest-news-for-doctors-nurses-and-pharmacists/ Sun, 18 Sep 2022 01:01:48 +0000 https://atrx.net/second-hand-smoke-during-the-first-trimester-increases-the-risk-of-coronary-artery-disease-in-infants-latest-news-for-doctors-nurses-and-pharmacists/ Mothers exposed to environmental tobacco smoke (ETS) during the first trimester of pregnancy are more likely to give birth to infants with congenital heart defects (CHD), according to a recent study. The researchers conducted a case-control analysis of 749 fetuses with coronary artery disease and 880 fetuses without. Logistic regression analysis revealed that exposure to […]]]>

Mothers exposed to environmental tobacco smoke (ETS) during the first trimester of pregnancy are more likely to give birth to infants with congenital heart defects (CHD), according to a recent study.

The researchers conducted a case-control analysis of 749 fetuses with coronary artery disease and 880 fetuses without. Logistic regression analysis revealed that exposure to ETS from 12 months before pregnancy through the first trimester increased the risk of coronary heart disease by almost 70% (adjusted odds ratio [OR]1.67, 95% confidence interval [CI]1.28–2.18).

Such ETS exposure patterns increased the odds of septal abnormalities (adjusted OR, 1.58, 95% CI, 1.18 to 2.12), conotruncal abnormalities (adjusted OR, 1.86, 95% CI, 1.21 to 2.84), left ventricular outflow tract obstructions (adjusted OR, 1.69, 95% CI, 1.15 to 2.48), left ventricular outflow tract obstructions right ventricular outflow tract (adjusted OR, 1.82, 95% CI, 1.25 to 2.67) and other types of coronary artery disease (adjusted OR, 2.73, 95% CI, 1, 65 at 4.51).

Of note, exposure to ETS had a dose-response effect on the risk of coronary artery disease in the offspring. Exposure levels less than 1 hour per day did not affect the likelihood of developing coronary artery disease, but exposure for 1–2 hours per day (adjusted OR, 1.60, 95% CI, 1.07 to 2.41) and ≥ 2 hours per day (adjusted OR, 4.94, 95% CI, 2.43 to 10.05) increased this risk.

“These findings underscore the importance of preplanned pregnancy and prevention, including folic acid supplementation, paternal smoking cessation, maternal avoidance of ETS and harmful harmful substances at home or on the premises. work,” the researchers said.

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What is the difference between batch and stream processing? https://atrx.net/what-is-the-difference-between-batch-and-stream-processing/ Tue, 13 Sep 2022 00:36:45 +0000 https://atrx.net/what-is-the-difference-between-batch-and-stream-processing/ The typical answer when someone describes the difference between batch processing and stream processing is that batch data is collected, stored for a period of time, and then processed and used at regular intervals (e.g. payroll, bank statements ) while streaming data is processed and be used closer to the time it is generated (think […]]]>

The typical answer when someone describes the difference between batch processing and stream processing is that batch data is collected, stored for a period of time, and then processed and used at regular intervals (e.g. payroll, bank statements ) while streaming data is processed and be used closer to the time it is generated (think alerts from sensor data).

While accurate, this answer fails to capture why the difference matters and why companies are moving aggressively towards stream processing architectures.

We experience the world as a constant flow of events. We make decisions by comparing this flow of information to our experiences and memories. We perceive and react to threats or recognize and seize opportunities. And often reacting in a timely manner is rewarding – we avoid the snakebite or get the best seat at the movies. Stream processing more accurately reflects this very human mode of experience.

Businesses ingest as many streams of information as they can handle, looking for patterns in the data that represent threats or opportunities as it flows, and when those patterns emerge, they act. The cost of inaction could be a data breach or a lost revenue opportunity.

Batch processing still works well when you need to process huge amounts of data and results can be delivered at regular intervals. But if recent trends continue, more of those jobs will shift to streaming as companies can no longer accept the hidden cost of the lot and stay competitive.

A good example is insider trading. The cost of detecting someone about to execute an insider trade is now much lower than the cost of trying to unwind that trade later when the batch process picks it up. Even though the batch runs every five minutes, that just means you’ll find them sooner, not stop them. Ultimately, the flow against the lot will show up in the balance sheet and stock price.

The only potential argument against streaming is that it might not handle the amount of data as cost-effectively as batch processing. However, with the advent of systems like Kafka, Flink and their cloud analogues, such cases are becoming rare.

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Camrelizumab/Rivoceranib improves PFS and OS compared to sorafenib for unresectable HCC https://atrx.net/camrelizumab-rivoceranib-improves-pfs-and-os-compared-to-sorafenib-for-unresectable-hcc/ Sat, 10 Sep 2022 17:59:42 +0000 https://atrx.net/camrelizumab-rivoceranib-improves-pfs-and-os-compared-to-sorafenib-for-unresectable-hcc/ Results presented at ESMO 2022 show survival benefits of camrelizumab plus rivoceranib in patients with unresectable HCC. Combined use of the PD-1 inhibitor camrelizumab and the VEGFR2 TKI rivoceranib significantly improved both progression-free survival (PFS) and overall survival (OS) compared to sorafenib (Nexavar) for patients with an unresectable hepatocellular carcinoma (HCC), according to the results […]]]>

Results presented at ESMO 2022 show survival benefits of camrelizumab plus rivoceranib in patients with unresectable HCC.

Combined use of the PD-1 inhibitor camrelizumab and the VEGFR2 TKI rivoceranib significantly improved both progression-free survival (PFS) and overall survival (OS) compared to sorafenib (Nexavar) for patients with an unresectable hepatocellular carcinoma (HCC), according to the results of a phase 3 study (NCT03764293) presented at the ESMO Congress 2022.1

Median OS with camrelizumab and rivoceranib was 22.1 months (95% CI, 19.1-27.2) versus 15.2 months with sorafenib (95% CI, 13.0-18.5 ), which was equivalent to a 38% reduction in the risk of death (RR, 0.62; 95% CI, 0.49-0.80; P < .0001). The median PFS with camrelizumab and rivoceranib was 5.6 months (95% CI, 5.5-6.3) versus 3.7 months for sorafenib (95% CI, 2.8-3.7 ), which corresponded to a 48% reduction in the risk of progression or death (HR, 0.52; 95% CI, 0.41-0.65; P < .0001).

“This is the first positive international Phase 3 study to report significant benefits in PFS and OS with the combination of immunotherapy and small molecule TKI compared to sorafenib for unresectable HCC said lead researcher Shukui Qin, MD, Department of Medical Oncology, Cancer Center. from Jinling Hospital in Nanjing, China, said during a presentation of the results. “Furthermore, camrelizumab plus rivoceranib provides the longest OS, at 22.1 months, observed in a pivotal first-line Phase 3 study in advanced HCC to date.”

In the Phase 3 study, patients were equally randomized to camrelizumab 200 mg intravenously every 2 weeks plus oral rivoceranib 250 mg daily (n=272) or oral sorafenib 400 mg twice times a day (n = 271). The median age of patients in the combination arm was 58 years versus 56 years in the sorafenib arm. Most patients in both groups were recruited from Asia (82.7%), with 47 patients in each group being non-Asian.

Baseline characteristics were similar in all arms. In the camrelizumab plus rivoceranib arm, most patients had stage C BCLC disease (86.8%), a majority had an ECOG performance status of 1 (55.9%), and AFP was 400 ng /ml or more for 35.3%. Gross vascular invasion and extrahepatic spread were observed in 73.5% of patients and the most common etiology was hepatitis B virus infection (76.5%). Just over half of the patients had received local therapy (59.2%) before entering the study.

The objective response rate (ORR) confirmed by a blinded independent review board and RECIST v1.1 criteria was 25.4% with camrelizumab plus rivoceranib versus 5.9% for sorafenib, representing superiority for association (P < .0001). These results were similar for ORR determined by the modified RECIST criteria, at 33.1% for the combination versus 10.0% for sorafenib (P < .0001). The median duration of response according to RECIST v1.1 was 14.8 months with camrelizumab plus rivoceranib and 9.2 months for sorafenib.

According to RECIST v1.1 criteria, there were 3 complete responses (CR) with camrelizumab plus rivoceranib versus 1 CR for sorafenib. Using the modified RECIST criteria, there were 14 CRs with the association versus 3 for the single agent. Including stable disease, the disease control rate (DCR) by RECIST v1.1 with the combination was 78.3%, compared to 53.9% for the single agent. These rates were similar under the modified criteria.

The 6-month PFS rate with camrelizumab plus rivoceranib was 44.6% versus 22.7% for sorafenib. For OS, 76.5% of patients were alive at 12 months in the camrelizumab plus rivoceranib arm, compared to 60.8% in the sorafenib arm. At month 18, the OS rate was 60.9% with the combination versus 45.2% with monotherapy.

These benefits were seen across all subgroups, Qin said. By geographic region, the relative risk for OS was 0.55 favoring the association in non-Asian patients. The small size of the population however limited the statistical analyses, with a very wide confidence interval observed (95% CI, 0.29-1.02). “PFS and OS generally favored camrelizumab over rivoceranib in all subgroups,” Qin noted.

Grade 3/4 treatment-related adverse events (TRAE) were experienced by 80.5% of patients in the camrelizumab plus rivoceranib arm versus 52% in the sorafenib group. There was 1 grade 5 ETRA in each treatment group. Serious AETRs were experienced by 24.3% of patients treated with the combination versus 5.9% in the single-agent arm. Dose modifications or interruptions for EITRs were required for 80.5% in the combination arm versus 50.2% in the monotherapy arm; however, discontinuation of all treatment components was similar between groups at 3.7% for camrelizumab plus rivoceranib versus 4.5% for sorafenib.

The most common Grade ≥ 3 TEAEs with camrelizumab plus rivoceranib were hypertension (37.5%), AST increased (16.5%), ALT increased ( 12.9%), palmar-plantar erythrodysaesthesia (EPI; 12.1%) and decreased number of platelets (11.8%). For sorafenib, the most common grade ≥3 TEAEs were PPE (15.2%) and hypertension (14.9%).

“The combination of camrelizumab plus rivoceranib was generally well tolerated, with a safety profile in line with each individual agent and the underlying disease,” Qin said. “These results confirm that camrelizumab plus rivoceranib represents another new first-line treatment option for unresectable HCC.”

During a discussion of the results, R. Katie Kelley, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, described the potential benefits of using an inhibitor of oral angiogenesis, but also cautioned that careful patient selection was needed given the hepatotoxicity seen with the combination. Additionally, she noted challenges with extrapolating the data to a non-Asian population, especially given the high rates of hepatitis B virus infection seen in the underlying etiology.

“The advent of multiple front-line and post-treatment options marks tremendous progress in HCC and provides a new opportunity to individualize treatment decisions,” Kelley said. “Region and etiology can impact the results of HCC trials involving immune checkpoint inhibitor therapies. population.

Along with the presentation, Elavar Therapeutics, the company developing the combination, announced its intention to work with the FDA on a potential path to approval. Additionally, the company plans to submit rivoceranib to the FDA for the treatment of recurrent or metastatic adenoid cystic carcinoma (ACC). Results for this indication were presented at the 2022 ASCO Annual Meeting, showing an investigator-assessed RECIST 1.1 ORR of 15.1% (95% CI, 7.8% at 25.00, 4%) with rivoceranib and a DCR rate of 64.4% (95% CI, 52.3%-75.3%).2

“Based on the positive results of the combined study, Elevar plans to work closely with the U.S. Food & Drug Administration for the submission of a new drug application. [NDA] for rivoceranib in combination with camrelizumab as a treatment option for HCC,” Saeho Chong, CEO of Elevar, said in a statement. “In addition, Elevar plans to submit a [new drug application] to the United States Food & Drug Administration for rivoceranib as a treatment option for ACC by the end of 2022.”

References

1) Qin S, Chan SL, Gu S, et al. Camrelizumab (C) plus rivoceranib (R) vs sorafenib (S) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): a phase III randomized trial. Anne Oncol. 2022;33(Supplement 7). doi:10.1016/j.annomnc.2022.08.032.

2) Kang H, Ahn MJ, Muzaffar J, et al. A Phase 2 study of the oral vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, rivoceranib, for recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). J Clin Oncol. 2022;40 (suppl 16):abstr 6020. doi:10.1200/JCO.2022.40.16_suppl.6020.

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A randomized trial of enteral glutamine for the treatment of burns https://atrx.net/a-randomized-trial-of-enteral-glutamine-for-the-treatment-of-burns/ Fri, 09 Sep 2022 09:18:09 +0000 https://atrx.net/a-randomized-trial-of-enteral-glutamine-for-the-treatment-of-burns/ From the Clinical Evaluation Research Unit (DKH, LO-R.) and Research Institute (AGD), Kingston Health Sciences Center and Departments of Critical Care Medicine (DKH, LOR) and Public Health Sciences (DKH) from Queen’s University, Kingston, ON, the Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Laval University, and the Unit […]]]>

From the Clinical Evaluation Research Unit (DKH, LO-R.) and Research Institute (AGD), Kingston Health Sciences Center and Departments of Critical Care Medicine (DKH, LOR) and Public Health Sciences (DKH) from Queen’s University, Kingston, ON, the Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Laval University, and the Unit of population health and optimal health practices (Trauma, emergency and intensive care medicine) and the Canada Research Chair in Critical Care in Neurology and Traumatology, Center hospitalier universitaire de Québec–Centre de recherche de l’ Université Laval, Québec, QC (AFT), Department of Surgery, Division of Plastic Surgery, Department of Immunology and Institute of Medical Sciences, University of Toronto, Ross Tilley Burn Centre, Sunnybrook Health Sciences Center and Sunnybrook Research Institute, Tor onto (MGJ), and the departments of medicine and anesthesiology (SB) and the department of nutrition, Faculty of Medicine (D. Garrel), University of Montreal, Montreal — all in Canada; the University of Iowa, Iowa City (LW); Mercy Hospital Burn Center, Mercy Hospital, St. Louis (JAP); Joseph M. Still Research Foundation, Augusta, GA (BF); Legacy Oregon Burn Center and Oregon Health and Science University, Portland (NE); internal medicine, Centro Nacional de Quemaduras y Cirugía Reconstructiva, Asunción, Paraguay (D. Grau); UT Southwestern Medical Center, Dallas (SM) and Joint Base San Antonio–Fort Sam Houston, San Antonio (JMG) – both in Texas; University of Tennessee Health Sciences Center and Firefighters Burn Center, Memphis (SRV); the Department of Hand, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Heidelberg (GH), and the Department of Anaesthesiology, Critical Care Medicine and Pain Therapy, Hospital University of Würzburg, Würzburg (CS ) — both in Germany; Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham (NM), Mersey Regional Burn Centre, St. Helens and Knowesley NHS Trust, Whiston Hospital, Prescot (KS), Manchester Metropolitan University, Manchester (KS) and plastic surgery and Burns, Chelsea and Westminster Hospital London, London (DC) — all in the UK; Arizona Burn Center Valleywise Health, Maricopa Medical Center, Phoenix (KF); the Department of Surgical Sciences, Plastic Surgery, Uppsala University, and the Burn Center, Department of Plastic and Maxillofacial Surgery, Uppsala University Hospital, Uppsala, Sweden (FH); Connecticut Burn Center, Yale New Haven Health/Bridgeport Hospital, Bridgeport (AS); and Centro Traumatologico Ortopedico, Azienda Ospedaliera Universitaria, Città della Salute e della Scienza di Torino, Turin, Italy (ND).

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Dapagliflozin Reduces CV Risk in Heart Failure with Preserved LVEF – Consumer Health News https://atrx.net/dapagliflozin-reduces-cv-risk-in-heart-failure-with-preserved-lvef-consumer-health-news/ Mon, 29 Aug 2022 16:22:28 +0000 https://atrx.net/dapagliflozin-reduces-cv-risk-in-heart-failure-with-preserved-lvef-consumer-health-news/ MONDAY, Aug. 29, 2022 (HealthDay News) — For heart failure patients with mildly reduced or preserved ejection fraction, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces the combined risk of worsening heart failure or cardiovascular death, according to a study published online August 27 in the New England Journal of Medicine to coincide with the […]]]>

MONDAY, Aug. 29, 2022 (HealthDay News) — For heart failure patients with mildly reduced or preserved ejection fraction, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces the combined risk of worsening heart failure or cardiovascular death, according to a study published online August 27 in the New England Journal of Medicine to coincide with the European Society of Cardiology Congress 2022, to be held August 26-29 in Barcelona, ​​Spain.

Scott D. Solomon, MD, of Brigham and Women’s Hospital, Boston, and colleagues randomly assigned 6,263 patients with heart failure and a left ventricular ejection fraction over 40% to receive either dapagliflozin, or a corresponding placebo, in addition to the usual treatment. The primary outcome, assessed in a time-to-event analysis, was a composite of worsening heart failure or cardiovascular death.

The researchers found that the primary outcome occurred in 16.4% of 3131 patients in the dapagliflozin group and 19.5% of 3132 patients in the placebo group (relative risk, 0.82; 95% confidence interval %, 0.73 to 0.92; P < 0.001). Worsening of heart failure occurred in 11.8 and 14.5% of patients in the dapagliflozin and placebo groups, respectively (relative risk, 0.79; 95% confidence interval, 0.69 to 0.91) , and cardiovascular death occurred in 7.4 and 8.3%, respectively (relative risk, 0.88; 95% confidence interval, 0.74 to 1.05). Compared to the placebo group, the total number of events and symptom burden were both lower in the dapagliflozin group.

“These data provide additional evidence to support the use of an SGLT2 inhibitor as a lifeline treatment in patients with heart failure, regardless of the presence or absence of type 2 diabetes mellitus or diabetes mellitus. left ventricular ejection fraction,” the authors write.

The study was funded by AstraZeneca, the maker of dapagliflozin.

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Use of nirmatrelvir and serious consequences of Covid-19 during the surge of Omicron https://atrx.net/use-of-nirmatrelvir-and-serious-consequences-of-covid-19-during-the-surge-of-omicron/ Wed, 24 Aug 2022 21:00:27 +0000 https://atrx.net/use-of-nirmatrelvir-and-serious-consequences-of-covid-19-during-the-surge-of-omicron/ Summary Background The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk unvaccinated patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.617.2 (delta). ). Data regarding the effectiveness of nirmatrelvir in preventing severe outcomes of coronavirus disease 2019 (Covid-19) variant B.1.1.529 (omicron) are limited. Methods We obtained data for all members […]]]>

Summary

Background

The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk unvaccinated patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.617.2 (delta). ). Data regarding the effectiveness of nirmatrelvir in preventing severe outcomes of coronavirus disease 2019 (Covid-19) variant B.1.1.529 (omicron) are limited.

Methods

We obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and who were assessed as eligible to receive nirmatrelvir treatment during the omicron surge. A Cox proportional hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions and previous immune status against SARS-CoV-2.

Results

A total of 109,254 patients met the eligibility criteria, of whom 3,902 (4%) received nirmatrelvir during the study period. Among patients aged 65 or older, the rate of hospitalizations due to Covid-19 was 14.7 cases per 100,000 person-days in treated patients compared to 58.9 cases per 100,000 person-days in untreated patients. treated (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death from Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients aged 40 to 64, the rate of hospitalizations due to Covid-19 was 15.2 cases per 100,000 person-days in treated patients and 15.8 cases per 100,000 person-days in untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death from Covid-19 was 1.32 (95% CI, 0.16 to 10.75).

conclusion

Among patients 65 or older, rates of hospitalization and death from Covid-19 were significantly lower in those who received nirmatrelvir than in those who did not. No evidence of benefit was found in young adults.

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