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Covid-19 Survey 6

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Kidney Cancer UK Accord Report

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Latest News

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  • DNA Break feat image

    Opdivo + Yervoy fails adjuvant phase 3 trial

    02 Aug 2022

    Bristol-Myers Squibb has revealed that its checkpoint inhibitor combination of Opdivo and Yervoy failed a phase 3 trial as adjuvant (post-surgery) therapy for renal cell carcinoma (RCC), the most common form of kidney cancer writes pharmaphorum.com

    The disappointing outcome from the CheckMate -914 trial undermines BMS’ hopes of moving PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab) treatment into earlier-stage cancers.

    Opdivo/Yervoy has been approved since 2018 as first-line treatment for patients with intermediate- and poor-risk advanced RCC, and BMS was hoping to extend the use of the regimen into patients with localised RCC tumours that are treatable with surgery.

    The new data come from Part A of the CheckMate -914 trial, which involved patients with localised RCC who had full or partial kidney removal surgery and were considered at moderate or high risk of the cancer coming back.

    The results showed that Opdivo/Yervoy was no better than placebo at improving disease-free survival, said BMS. Part B of the trial is investigating Opdivo alone versus placebo in this setting and will continue to read out, although now looks likely to disappoint.

    It’s a blow to BMS’ particularly as its arch-rival in the PD-1 inhibitor category – Merck & Co – recently scored approval for its drug Keytruda (pembrolizumab) as adjuvant RCC.

    “Even with notable progress in the treatment of metastatic renal cell carcinoma, there are still limited treatment options available for patients with localised disease,” said BMS’ Dana Walker, who heads up the drugmaker’s genitourinary cancer development programmes.

    She noted that Opdivo and Opdivo/Yervoy have previously been shown in trials to be effective as adjuvant therapy for other cancers, including genitourinary tumours.

    That includes bladder cancer for example, where Opdivo was approved last year for use after surgery in patients with muscle-invasive urothelial carcinoma (UC), as well as for oesophageal/gastro-oesophageal cancer and melanoma.

    Securing approvals in the adjuvant or neo-adjuvant (pre-surgery) setting is a key strategy for BMS and other checkpoint inhibitor developers, as it allows them to position their drugs as the earliest cancer immunotherapy option in the treatment pathway.

    Opdivo and Opdivo/Yervoy have also shown a benefit in clinical trials alongside Exelixis’ tyrosine kinase inhibitor Cabometyx (cabozantinib) as first-line therapy in advanced RCC, while Opdivo proved to be effective as second-line treatment.

    BMS said it is also investigating Opdivo and Opdivo plus Yervoy in combination with novel agents targeting alternative immunomodulatory molecules and pathways in RCC.

    Meanwhile, other pharma companies are also developing checkpoint inhibitors for adjuvant RCC, including Roche whose Tecentriq (atezolizumab) is in the phase 3 IMmotion010 study, and AstraZeneca which is testing its Imfinzi (durvalumab) alone and in combination with CTLA4 drug tremelimumab in the RAMPART trial.

    Read this story on pharmaphorum.com

  • VHL Research feat image

    New Approach to Treating VHL RCC

    29 Jul 2022

    The research could be used to develop more targeted kidney cancer drugs.

    Researchers from Sweden’s Karolinska Institutet have discovered a connection between reduced mitochondrial content in cells and resistance to treatment for a lethal type of kidney cancer. The cancer cells reacted to the treatment when the researchers used an inhibitor to boost the mitochondrial content. Their research, which was published in Nature Metabolism, raises the possibility of more targeted cancer treatments.

    In order to create energy for the cell, mitochondria need oxygen. They are the part of the cell that uses the most oxygen as a result. However, it is still unclear how mitochondria adjust to a low-oxygen environment and are related to resistance to cancer treatments.

    “We’ve shown for the first time how the formation of new mitochondria is regulated in cells that lack oxygen and how this process is altered in cancer cells with VHL (von hippel-lindau) mutations,” says Associate Professor Susanne Schlisio, group leader at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

    Healthy cells are prevented from becoming cancerous by a gene called von Hippel-Lindau (VHL). The 2019 Nobel Prize in Physiology or Medicine was awarded to the discovery that VHL was part of the cell’s oxygen detection system. Normally, VHL breaks down another protein called HIF. Consequently, when VHL is mutated, HIF accumulates and causes a disease called VHL syndrome in which the cells react as if they lack oxygen despite oxygen being present. VHL syndrome greatly increases the risk of tumors, both benign and malignant. VHL syndrome-induced kidney cancer has a poor prognosis, with a five-year survival rate of barely 12%.

    In the present study, the researchers examined the protein content of cancer cells from patients with different variants of VHL syndrome, and how they differed from another group of individuals with a special VHL mutation called Chuvash, a mutation involved in hypoxia-sensing disorders without any tumor development. Those with the Chuvash VHL-mutation had normal mitochondria in their cells, while those with VHL syndrome mutation had few.

    To increase the amount of mitochondrial content in VHL-related kidney cancer cells, the researchers treated these tumors with an inhibitor of a mitochondrial protease called “LONP1”. The cells then became susceptible to the cancer drug sorafenib, which they had previously resisted. In mouse studies, this combination treatment led to reduced tumor growth.

    “We hope that this new knowledge will pave the way for more specific LONP1 protease inhibitors to treat VHL-related clear cell kidney cancer,” says the study’s first author Shuijie Li, a postdoctoral researcher in Schlisio’s team. “Our finding can be linked to all VHL syndromic cancers, such as the neuroendocrine tumors pheochromocytoma and paraganglioma, and not just kidney cancer.”

    To read the full story visit scitechdaily.com

  • Laura Wilkinson 2 edit

    Covid-19 Survey 6

    28 Jul 2022

    6th Kidney cancer patient Covid-19 survey shows growing patient confidence

    • 61% only wear facemasks in crowded places
    • 54% say they were now ‘not’ or ‘a little concerned’ of contracting Covid-19
    • 62% of those surveyed are back to face-to-face medical appointments

    – Published July 2022

    Results of the 6th Kidney Cancer Patient Covid-19 Survey show growing patient confidence in dealing with and the fight back against the pandemic.

    Over 90% of kidney cancer patients surveyed took up the offer of a vaccine and boosters with just under 10% declining. 49% contracted Covid-19 with 54% having full recovery while 20% felt they have what they feel to be long-covid.

    For 61% of the kidney cancer patients surveyed, facemasks remain in use ‘mostly in crowded places like shops, public transport while 22% say they never wear a mask now and 6% wear one when they remember. 11% wear a mask from leaving to returning home.

    Of the kidney cancer patients who tested positive for Covid-19, 69% were contacted by NHS but 25% received no contact from NHS. Only 20 % who were immunosuppressive were offered antiviral medication which for the majority arrived within three days though, 100% of those who received the medication said it reduced symptoms.

    For the first time in the series of surveys, when we asked ‘How anxious do you feel about Covid-19 today – Not at all, A little, Concerned, Anxious and very anxious’ the reply was almost 40% saying they were ‘a little concerned’ with 32% saying concerned. We had a similar reply when asking the same question relating to their kidney cancer; 44% saying ‘a little’ and 24% replying ‘concerned’. And what do they feel their chance of catching Covid-19 is today? 74% replied ‘ low’ or ‘medium’ with 25% saying ‘high’, 1% don’t know.

    Face-to-face appointments are on the rise, too. 62% of those surveyed are back to face-to-face appointments and the remainder are mostly (88%) receiving telephone consultation.

    Nick Turkentine, CEO Kidney Cancer UK said: “We are encouraged to see how kidney cancer patients have adjusted to the new normal of living with Covid-19, though this is by no means a time to become complacent. The autumn and winter will almost certainly see cases raise further and kidney cancer patients need to be extra vigilant, ensuring they are up to date on any boosters and protected to the level needed to keep them safe through the colder months when we are all more susceptible to the virus.”

    He concluded, “If you do contract Covid-19 and you are on immunosuppressive treatment, make sure you report your positive test to the NHS and receive the antiviral medication which seems to be very effective according to the survey.”

    To see our previous Covid-19 Surveys go to our library HERE

  • Covid 19 vaccine vials FEAT

    4th COVID-19 vaccine safe for immunocompromised

    27 Jul 2022

    A fourth dose of mRNA COVID-19 vaccine seems safe for immunocompromised individuals aged 12 years or older, according to research published in the July 15 issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report.

    Anne M. Hause, Ph.D., from the CDC COVID-19 Emergency Response Team, and colleagues characterized the safety of a first booster dose (dose 4) at least three months after dose 3 and a second booster dose (dose 5) at least four months after dose 4 among immunocompromised persons aged 12 years or older during Jan. 12, 2022, to March 28, 2022. Adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) were reviewed. During the study period, about 518,113 persons received a fourth dose.

    The researchers found that local and systemic reactions were less frequently reported among 4,015 v-safe registrants after the fourth dose compared with after dose 3 of the primary vaccination series. VAERS received 145 reports after fourth doses: 88.3 and 11.7 percent were nonserious and serious, respectively.

    “Preliminary safety findings for booster doses among persons with presumed immunocompromise are similar to those among nonimmunocompromised persons; reactions are reported less frequently after booster vaccination than after the last dose of a primary series,” the authors write. “It is important that health care providers, immunocompromised persons, and parents of immunocompromised children be advised that local and systemic reactions are expected after a booster dose, and that serious adverse events are rare.”

     

    Read the full story at MedicalExpress.com

  • Savolitinib kidney pills feat header

    Savolitinib not significantly efficacious in aRCC

    27 Jul 2022

    Savolitinib, alone or in combination with durvalumab, did not demonstrate significant efficacy in patients with advanced clear cell renal cancer, according to a presentation at ASCO Annual Meeting.

    “We know drugs like cabozantinib have multiple activities, including MET, but savolitinib is a potent mass inhibitor. And so it has an established dose, and exploring it in metastatic clear cell renal cancer is reasonable,” Thomas Powles, MBBS, MRCP, MD, professor of genitourinary oncology, lead for solid tumor research and director of Barts Cancer Centre at St. Bartholomew’s Hospital in London, England, said during the presentation. “We know more about CTLA-4. Tremelimumab is a CTLA-4 inhibitor, but again, it’s not been widely explored in metastatic clear cell renal cancer.”

    “So, in this study, we explored the combination of savolitinib-durvalumab or tremelimumab-durvalumab in VEGF-resistant clear cell [renal cancer]. Durvalumab alone is included as a component part, and we also explore a number of biomarkers in a subset of this study.”

    Between 2017 and 2021, Powles and colleagues included 139 patients with advanced clear cell renal cancer, who had previously received VEGF targeted therapy but not immune checkpoint inhibitors or MET inhibitors, within the study. They randomized patients to receive either durvalumab (D), savolitinib (S), durvalumab and tremelimumab (DT), or durvalumab and savolitinib (DS). The primary endpoint of the study was confirmed response rate, with a response rate of at least 50% required for further exploration. Researchers closed the S arm early due to a lack of efficacy.

    “Savolitinib alone, or in combination with durvalumab, did not meet predefined activity levels. This also appeared to be the case in MET-driven tumors,” Powles said. “The addition of tremelimumab to durvalumab did not clearly improve efficacy.”

    Read the full story on healio.com

  • Screening

    Statins improve effectiveness of nivo for advanced kidney cancer

    12 Jul 2022

    Statins are widely used in an ageing population, including subjects with solid malignancies. However, no conclusive evidence is currently available on their potential influence on patients’ outcome. We aimed to assess whether statin exposure affects the survival of patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.

    Medical records of patients with documented mRCC treated with second- or third-line nivolumab were reviewed at ten institutions from Italy, Spain and the USA. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit. Univariate and multivariate analyses were used to explore the association of variables of interest with survival.

    A total of 219 patients with mRCC receiving nivolumab between January 2016 and September 2021 were eligible for inclusion in this study; 59 (27%) were statin users. The median OS (34.4 versus 18.6 months, p = 0.017) and PFS (11.7 versus 4.6 months, p = 0.013) resulted apparently longer in statin users. Stratified by age, longer median OS and PFS were associated with statin exposure in both patients aged ≥70 y (median OS: 21.4 versus 10.1 months, p = 0.047; median PFS: 16.4 versus 4.6 months, p = 0.022) and <70 y (median OS: 34.4 versus 21.4 months, p = 0.043; median PFS: 10.3 versus 4.6 months, p = 0.042). Overall clinical benefit resulted higher in statin users than non-users (71% versus 54%, p = 0.030).

     

    READ THE FULL ARTICLE ON UROTODAY HERE

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