Geneology International

Tag: Trials

  • From Clinical Trials to Real-World Practice, Experts Examine the Best Options for TNBC

    From Clinical Trials to Real-World Practice, Experts Examine the Best Options for TNBC

    CancerNetwork® recently hosted a first-of-its-kind Tweet Chat with co-hosts Hope S. Rugo, MD, and Paolo Tarantino, MD. Together, they reviewed a patient case of a 52-year-old woman who had been diagnosed with stage IIA triple-negative breast cancer (TNBC) and went into detail regarding treatment options for the metastatic population.

    Rugo, a professor of medicine, and director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Comprehensive Cancer Center; and Tarantino, a Clinical Research Fellow at Dana-Farber Cancer Institute, also examined the use of neoadjuvant therapeutics for early disease and potential adjuvant therapy-sparing regimens.

    During the live Tweet Chat, both experts detailed the impact of antibody-drug conjugates (ADCs) on survival outcomes and the best approach for treating patients following disease recurrence after first-line therapy.

    In the first part of the patient case of a 52-year-old woman with stage IIA TNBC, Rugo mentioned the need for neoadjuvant chemotherapy, “We recommend [neoadjuvant chemotherapy] in this case, following the KN522 regimen. The [addition] of [pembrolizumab increases] pCR and EFS. @SABCS22 Gupta showed better outcomes adding platinum to T/[adjuvant chemotherapy].”

    Tarantino responded with results from the phase 3 KEYNOTE-522 trial (NCT03036488) wherein patients with TNBC received pembrolizumab (Keytruda) plus chemotherapy vs placebo as a neoadjuvant treatment and pembrolizumab vs placebo as adjuvant treatment.1

    Rugo questioned if there is a need to wait a year after starting pembrolizumab for a partial complete response (pCR) to be observed and, if not, whether capecitabine/pembrolizumab is a good alternative treatment option.

    Additionally, she introduced several studies assessing sacituzumab govitecan-nxki (Trodelvy) in patients with TNBC, “OptimICE pCR is an ALLIANCE trial that will randomize [patients] to [pembrolizumab] or not in those with pCR. OptimICE RD and the [phase 3] SASCIA trial [NCT04595565] are evaluating the addition of sacituzumab govitecan in patients with residual disease.”

    In response, Tarantino discussed data from phase 2 GeparNuevo trial (NCT02685059) which added a PD-L1 antibody to taxane chemotherapy.2 In this trial, patients had a high invasive disease-free survival. While OptimICE-pCR is still enrolling patients, he hopes that the results will show the ability to spare adjuvant immunotherapy.

    Next steps of treatment was also a topic of conversation, as the patient experienced recurrence after adjuvant capecitabine and radiation.

    Tarantino responded that chemotherapy and taxane rechallenge is the current standard of care for recurrent TNBC, “[Chemotherapy], with a taxane rechallenge [is] reasonable given [the] long time since completion of [adjuvant taxane].”

    When asked if she agreed with his reasoning behind using taxane in the first-line setting and sacituzumab govitecan in the second-line, Rugo mentioned the phase 3 ASCENT trial (NCT02574455), which had final data read out at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, supported this thought process She mentions that this trial then led to the approval of sacituzumab govitecan in the second-line setting for patients with TNBC.3,4

    Another study that was presented at ASCO and, according to Tarantino, showed impressive results was the phase 3 DESTINY-Breast04 trial (NCT03734029) which analyzed fam-trastuzumab deruxtecan-nkxi (Enhertu) in patients with HER2-low breast cancer.5

    In response to data from the DESTINY-Breast04 trial that Tarantino presented, Rugo said, “Really incredible data from DB04 for HR+ and encouraging in TNBC; just [important] to remember that [there were] only 58 pts so 18 in the control arm. And only 1/3 of TNBC [cases] are HER2 low.”

    Rugo also mentioned the ongoing phase 3 ASCENT-03 trial (NCT05382299) examining sacituzumab govitecan vs physician’s choice therapy in previously untreated metastatic TNBC. There is also the phase 3 ASCENT-04 trial (NCT05382286) assessing sacituzumab govitecan plus pembrolizumab vs physician’s choice plus pembrolizumab previously untreated, locally advanced inoperable or metastatic TNBC. Both of these trials utilized sacituzumab govitecan as second-line treatment.

    Tarantino and Rugo also touched on trials involving ADCs such as the phase 1/2 BEGONIA trial (NCT03742102), assessing durvalumab (Imfinzi), capivasertib, oleclumab, paclitaxel, trastuzumab deruxtecan, and datopotamab deruxtecan for patients with metastatic TNBC.6 To better support the data presented with BEGONIA, Tarantino posted a graphic detailing the change from baseline target lesion size and the change from baseline of the number of target lesions over time.

    When asked how they would treat a patient if progression occurred 3 months after initial treatment with first-line therapy, Rugo responded, “Good question, and tragic situation; in this case, we treat as if we are second line, so [we] would use sacituzumab govitecan first-line. At least that is my approach. @PTarantinoMD?If PD-L1 positive how would you treat?”

    Tarantino noted that if a patient is PD-L1 positive, it is worth it to combine first-line pembrolizumab plus chemotherapy. He referenced the phase 3 KEYNOTE-355 trial (NCT02819518) as an example of when to use this treatment combination.7

    Rugo agreed with Tarantino’s recommended course of action, but questioned if the patient was on single arm pembrolizumab at the time of progression, what should be the standard of care? Tarantino noted this was a hard question but said that he would be inclined to administer treatment as though the patient was in the second line, moving to an ADC.

    He then inquired if the patient had a BRCA mutation, would it change the choice of treatment.

    Rugo responded with results from the phase 3 OlympiAD trial (NCT02000622) that focused on the use of olaparib in patients with a BRCA mutation.

    Survival was also improved in the phase 3 EMBRACA trial (NCT01945775), assessing talazoparib in patients with advanced breast cancer who had a germline BRCA mutation.

    In closing, Rugo said she is interested in seeing outcomes with the use of maintenance PARP inhibitors after response is achieved, specifically those with BRCA mutations. Tarantino responded that PARP maintenance is a very interesting strategy and could even have use in other populations outside of those with BRCA mutations.

    To view the full Tweet Chat, visit, https://bit.ly/3XKj1bk

    References

    1. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549
    2. Loibl S, Schneeweiss A, Huober J, et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022;33(11):1149-1158. doi:10.1016/j.annonc.2022.07.1940
    3. Final data from phase 3 ASCENT study demonstrates Trodelvy extends overall survival over chemotherapy in second-line metastatic TNBC. News release. Gilead. June 6, 2022. Accessed January 27, 2022. https://bit.ly/40aDYh8
    4. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 7, 2021. Accessed January 27, 2023. https://bit.ly/3Hae98x
    5. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022; 387(1):9-20. doi:10.1056/NEJMoa2203690
    6. Loibl S, Schneeweiss A, Huober J, et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022;33(11):1149-1158. doi:10.1016/j.annonc.2022.07.1940
    7. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809
  • Many Clinical Trials Are Testing Whether Cannabis CBD Could Be an Effective COVID-19 Treatment

    Many Clinical Trials Are Testing Whether Cannabis CBD Could Be an Effective COVID-19 Treatment

    Let us get this out of the way now: You should not just take CBD to protect against COVID-19. You really should not smoke weed to avert COVID-19—in fact, that will likely make items worse. You surely need to not drink CBD seltzers or consider gummies to defend on your own from a virus that has the potential to destroy you—especially when there are vaccines that are proven to guard you.

    At the exact time, it can also be genuine that CBD from cannabis has a purpose to participate in in this pandemic—from dealing with COVID specifically, to working with the pandemic’s emotional facet effects. We’re presently observing this possible teased out in a flourish of new scientific research.

    Last week, experts posted findings suggesting CBD could possibly quit the coronavirus from replicating within cells. They also located that people approved CBD-dependent medication for epilepsy had reduce COVID-19 positivity rates than individuals who hadn’t been prescribed CBD, an early sign that this could keep up in the serious entire world. This was incredibly hot off the heels of yet another new study suggesting two other hashish compounds could bind to the coronavirus’ spike protein—stopping it from getting into cells in the first area.

    “When COVID very first begun, there was a great deal of fascination in the likely for cannabidiol [to] treat COVID patients, at that time there was scant information to hang our hat on,” Ziva Cooper, the director of the UCLA Hashish Research Initiative, told The Everyday Beast. “Then listed here are two examples, the two published in just a week, that demonstrate maybe there is some promise.”

    The bottom line for these two studies was the identical: We require extra clinical trials on CBD and COVID-19. The fantastic news is that there are some trials previously in the will work. At the minute there are presently 7 clinical trials registered with ClinicalTrials.gov that are investigating CBD in connection with COVID-19, and numerous additional in development elsewhere, The Day by day Beast has realized.

    Some reports have investigated the function of CBD in dealing with acute COVID-19 (that is, the time period of time when you have signs and symptoms). Other individuals are investigating how CBD could treat the extant outcomes of COVID skilled effectively just after the an infection is by now cleared out the overall body (also known as “long COVID”). Eventually, a third vein of investigation is looking into whether or not CBD can enable persons grappling with the emotional burnout prompted by the pandemic.

    There is however a lot we don’t know about what CBD can do for COVID, but its opportunity application retains setting up with every single new round of studies being printed. We need to figure out what its purpose will be—perhaps quicker than we believe.

    Preliminary An infection

    The concept that hashish could help deal with the results of COVID-19 isn’t in particular new. A person early principle all through the 1st days of the pandemic was that the anti-inflammatory results of CBD (the frequent title for cannabidiol, a key non-psychoactive compound in hashish), could possibly lower the impression of cytokine storms—intense immune process reactions that lead to COVID-19’s daily life threatening signs and symptoms.

    “If CBD may possibly be valuable for that, then fundamentally, it could potentially avoid greater severity of condition and avert the reduction of existence in selected conditions,” stated Cooper.

    Influenced by this idea, José Alexandre de Souza Crippa, a psychiatrist at Ribeirão Preto Healthcare School at the University of São Paulo, conducted a clinical demo on CBD and acute COVID infection all through Brazil’s winter season 2020 COVID-19 wave. Their analyze adopted 91 people with delicate-to-average COVID 28 days. 50 percent received CBD and 50 {fe463f59fb70c5c01486843be1d66c13e664ed3ae921464fa884afebcc0ffe6c} got a placebo. But the analyze located CBD experienced no serious result on the illness.

    Crippa has held pursuing these individuals for a year. Nevertheless, the benefits have not modified: “We had fantastic expectations for the acute period [trials] but we did not see that,” he advised The Day-to-day Beast.

    That stated, this line of inquiry is significantly from shut. Cooper points out that clients tolerated CBD nicely, which indicates it is secure to preserve these scientific studies likely. And, the individuals in these research got low doses of CBD.

    “There is a window of opportunity below to go up and use a significantly larger dose of cannabidiol in that individual inhabitants to figure out if it may have an effect on COVID symptomatology,” stated Cooper.

    CBD for the Extended Haul

    Undeterred, Crippa has pivoted to investigating CBD’s effects on lengthy COVID—in which patients are debilitated for many months by indicators like problems, malaise, extreme fatigue, difficulty concentrating, and shortness of breath. He’s conducting MRI scans on 3 teams: people handled with CBD and identified with COVID from his earlier analyze a placebo group who experienced COVID but didn’t get CBD and a third team of people today who have never tested positive for COVID.

    Crippa’s rationale is that CBD could have some protecting consequences when it comes to nervousness and depression, widespread problems in long COVID patients. He’s also intrigued in irrespective of whether CBD, which has proven neuroprotective consequences in Parkinson’s individuals, could reduce brain fog involved with lengthy COVID.

    “We have previously carried out scientific studies in animals, and cannabidiol seems to have a neuroprotection and anti-cognitive deficit influence, which is a essential difficulty in very long COVID,” explained Crippa. “So it’s reasonable to infer that cannabidiol may prevent this in the extensive-term.”

    But, he cautioned that fair anticipations really don’t imply this concept will pan out. “It’s trial and error,” he stated.

    Courtesy Imperial School London

    Crippa’s team isn’t the only a person intrigued in what cannabis-based medicine could do for extended COVID. Drug Science British isles, a non-profit group led by Imperial College or university London neuropsychopharmacologist David Nutt, is in the early levels of a clinical demo that will give 30 prolonged COVID individuals accessibility to a CBD-dominant formulation of professional medical cannabis identified as MediCabilis (a liquid merchandise made by Bod Australia) and see how properly they tolerate the drug from February by June.

    The highlight on this analyze is in particular vibrant thanks to the participation of Nutt, widely-regarded as a longtime advocate for drug research who was dismissed from the U.K.’s Advisory Council for the Misuse of Medicines in 2009 for his feeling that MDMA is a lot less unsafe than horseback riding and liquor. (These times, MDMA is remaining investigated as a “breakthrough drug” for PTSD).

    David Badcock, the CEO of Drug Science United kingdom, claimed the group is enterprise the analyze since very long COVID sufferers encounter indications like pain, stress, sleeplessness, and substantial blood tension or coronary heart rates—symptoms which are also observed in circumstances managed with professional medical hashish. (For instance, an earlier analyze run by the group uncovered that soon after a few months of medical cannabis entry, 75 patients with stress and anxiety, long-term agony, PTSD or MS saw improves in good quality of life scores.)

    “As there is no set up health care procedure for the [long COVID] ailment, we felt it was vital to research every single feasible possibility for people who’ve turn out to be ill all through the pandemic—including medical hashish,” he instructed The Day by day Beast.

    All of this research is even now in its early phases. Crippa is in the middle of analyzing his details, and the trial operate by Drug Science United kingdom is continue to only just to establish if it’s risk-free for very long COVID patients to acquire healthcare cannabis. If absolutely nothing goes erroneous, Nutt and his team will scale up the analyze into a randomized controlled demo.

    From Physical to Mental

    Irrespective of whether or not it turns out CBD can enable us take care of COVID symptoms, its major prospective appears to be in assisting us offer with the pandemic’s psychological toll. Nervousness is 1 area wherever CBD has robust potential many thanks to a “convergence” of pre-medical evidence, Steven Laviolette, a professor in anatomy and mobile biology at Western University in Canada, told The Day by day Beast.

    Laviolette has earlier shown that CBD can block the formation of panic-linked recollections in rats, since it interacts with serotonin signaling pathways in the brain. “Serotonin, of course, is actually crucial for anxiety and mood conditions,” he told The Everyday Beast. “Most of the major medications that treat individuals conditions focus on the serotonin program, so it truly is quite promising that CBD also seems to develop anti anxiousness results for the serotonin pathway.”

    Steven Laviolette (left).

    Courtesy Western College

    Suitable now, there are at minimum two trials underway at the College of Texas at Austin hunting to investigate the consequences of CBD on psychological coping during the pandemic. But Crippa’s team has also previously released function that confirmed how CBD helped burned-out medical center workers cope with strain.

    All through the acute COVID examine in Brazil, Crippa also ran a study on 118 frontline health and fitness-treatment personnel at Ribeirão Preto Health-related College University Medical center. 50 percent the patients took 300 mg of CBD along with regular cellphone calls with a psychiatrist and motivational films. The other team just acquired the cellular phone phone and online video procedure.

    In comparison to the placebo group, the CBD team noticed considerable reductions in their psychological exhaustion, and stress scores. “After this a person month, it was distinct that the group that been given cannabidiol did considerably far better,” said Crippa.

    Science Claims…

    On the other hand, new investigate is typically an possibility for men and women to press unproven suggestions about cannabis on to the general public. The U.S. Food items and Drug Administration, for occasion, has experienced to issue warning letters to CBD companies who falsely assert that their merchandise treat or defend towards COVID.

    Both equally Cooper and Crippa cautioned that the CBD most people obtain at a retail outlet is virtually absolutely not the same stuff offered to individuals in scientific trials, which need to be manufactured in accordance to Food and drug administration tips analyzed for purity and not known substances. Scientists know accurately how much CBD is in just about every dose—something that is not always accurate of in excess of the counter CBD products and solutions.

    In other terms it is not the exact things you can invest in at a dispensary, enable by yourself a fuel station.

    Even though investigation into professional medical cannabis and CBD would seem to have far too substantially momentum to grind to a halt, snake oil salesmen can gradual it down and create agonizing hurdles out of slender air. And there are already limitations that make this kind of analysis hard ample.

    “Given the socio-cultural history of candidates and then the reluctance among the sort of the set up psychiatric neighborhood to be far more open up minded in the direction of hashish based mostly pharmacotherapies it is been tough,” stated Laviolette. “We definitely require to have a more robust investment decision for analysis into this spot, and a lot less and much less pink tape as perfectly.”

    At the instant we still really don’t know accurately what job, if any, CBD will play in working with COVID-19 or its psychological aftermath. But there is absolutely plenty of exploration to say it is really worth discovering much more.

    “It appears to be like proper now we’re very considerably from understanding exactly what we can cling our hat on,” Cooper said. “But, you know, this is how science operates. You get some hits, you get some indicators. And then other scientific studies are crafted off of that.”