Latest news with #JournalOfClinicalOncology
Yahoo
14-07-2025
- Health
- Yahoo
Verastem's avutometinib combination shows 31% ORR in ovarian cancer trial
Verastem Oncology has reported primary analysis data from the two-part multicentre Phase II RAMP 201 trial, demonstrating that avutometinib plus defactinib showed a confirmed overall response rate (ORR) of 31% in treating recurrent low-grade serous ovarian cancer (LGSOC) patients. The analysis was published in the Journal of Clinical Oncology (JCO). The parallel cohort, adaptive, open-label, randomised study assessed avutometinib alone and in conjunction with defactinib in those with recurrent LGSOC. These patients had undergone a median of three previous therapy lines, including hormonal therapy, chemotherapy, bevacizumab, and MEK inhibitors. Part A of the trial determined the choice of the go-forward regimen, which was the combination therapy against avutometinib alone, based on ORRs. Parts B and C, the trial's expansion phases, assessed the safety and efficacy of the go-forward regimen of 3.2mg of avutometinib bi-weekly, and 200mg of defactinib twice a day. Part D of the trial assessed a low dose of the combination to inform the reduction of the individualised dose. The data published stated that the combination resulted in an ORR of 31% in 109 evaluable subjects in the trial. The response rate was also higher in those with a KRAS mutation, at 44%, compared to 17% in KRAS wild-type patients. The median duration of response (DOR) was reported to be 31.1 months across all subjects, with similar results seen in the KRAS mutant population. Despite this, the KRAS wild-type population had a shorter median DOR of 9.2 months. Median progression-free survival (PFS) was 12.9 months for all subjects, extending to 22 months in the KRAS mutant population and 12.8 months in the KRAS wild-type population. The disease control rate (DCR) at six months or more was 61% in the total population, with a higher rate of 70% in the KRAS-mutated group and 50% in the KRAS wild-type group. Most patients, regardless of KRAS mutation status, experienced some minimisations in target lesions. Last year, Verastem announced the dosing of the first subject with GFH375/VS-7375 as part of a Phase I/II trial in China. "Verastem's avutometinib combination shows 31% ORR in ovarian cancer trial" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. 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
Medscape
02-06-2025
- Health
- Medscape
Brain Tumors Clinical Practice Guidelines (2025)
Editorial Note: These are some of the highlights of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference. Updated guidelines on therapy of adult diffuse astrocytic and oligodendroglial tumors were published in April 2025 by the American Society of Clinical Oncology and the Society for Neuro-Oncology in the Journal of Clinical Oncology .[1] In patients with oligodendroglioma that is IDH -mutant, 1p19q co-deleted, central nervous system (CNS) World Health Organization (WHO) grade 2, offer radiation in combination with procarbazine, lomustine (CCNU), and vincristine (PCV). If toxicity is a concern, temozolomide is a reasonable alternative to PCV. Consider offering vorasidenib to patients who have oligodendroglioma that is IDH -mutant, 1p19q codeleted, CNS WHO grade 2; who have undergone one or more surgeries; and in whom further treatment with radiation and chemotherapy has been or can be deferred. In astrocytoma that is IDH -mutant, 1p19q non-codeleted, CNS WHO grade 2, initial radiation therapy and chemotherapy (with temozolomide or PCV) may be deferred until radiographic or symptomatic progression in some patients with favorable prognostic factors (eg, complete resection, younger age) or concerns about short- and long-term toxicity. Consider offering vorasidenib in patients who have astrocytoma that is IDH -mutant, 1p19q non-codeleted, CNS WHO grade 2; who have undergone one or more surgeries; and in whom further treatment with radiation and chemotherapy has been or can be deferred. For more information, please go to Brain Neoplasms.
Medscape
01-06-2025
- Business
- Medscape
Tumor Treating Fields Boost Pancreatic Cancer Survival
The addition of low-intensity electric tumor treating fields (TTFields) therapy to first-line standard chemotherapy was associated with significantly improved overall survival in a phase 3 trial for patients with unresectable, locally advanced, pancreatic adenocarcinoma (LA-PAC). The PANOVA-3 trial 'establishes tumor treating fields with gemcitabine/nab-paclitaxel as a potential new standard treatment paradigm for unresectable, locally advanced pancreatic cancer,' reported Vincent J. Picozzi, MD, first author of the new research, at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting. The new study, which was simultaneously published in the Journal of Clinical Oncology , is the first phase 3 trial to show an overall survival (OS) benefit for any treatment added to standard chemotherapy in this patient population, where the current 5-year OS rate is less than 8%, said Picozzi in his presentation. TTFields is a non-invasive therapy that delivers electricity to the tumor site via a wearable device and transducer arrays placed on the skin. The electric fields 'disrupt processes critical for cancer cell division and may do a variety of other things, such as trigger an enhanced anti-tumor response,' he explained. The therapy has already been approved in the United States and Europe for use in various cancers, including glioblastomas, metastatic pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). Study Methods The open-label study, conducted across 20 countries and 196 sites, included 571 patients with unresectable, locally advanced, biopsy-confirmed, and previously untreated pancreatic adenocarcinoma. Participants had a life expectancy of at least 3 months and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. The patients (median age 67 years, 47.6% male) were randomly assigned to receive only gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle (n = 286), or the same chemotherapy plus TTFields (n = 285). Patients wore the devices about 15 hours per day for about 28 weeks on average. Notably, almost 30% of the patients were non-White, almost 4% were ECOG PS 2, 'and perhaps most importantly, almost 30% had CA 19-9 levels greater than 1000, suggesting a high incidence of occult, unrecognized metastatic disease,' said Picozzi, a hematologist-oncologist and director of the Pancreaticobiliary Program at Virginia Mason Medical Center, Seattle, Washington. Follow-up visits were every 4 weeks, with chest, abdomen, and brain CT or MRI performed every 8 weeks to assess disease progression. Study Results After a median follow-up of about 13 months, the primary endpoint of OS was statistically improved in the TTFields arm compared with controls (16.2 vs 14.2 months, hazard ratio [HR] 0.82, P = .039), and the 1-year survival rate was similarly better (68.1% vs 60.2%; P = .029). There was no significant difference between groups in median progression-free survival (PFS), at 10.6 vs 9.3 months, respectively. However, the 1-year PFS rate was higher in the TTFields arm (43.9% vs 34.1%, P = .026). 'Perhaps somewhat surprisingly,' a post-hoc analysis showed a statistically significant benefit to TTFields in distant PFS, Picozzi said. Importantly, TTFields showed benefit in quality of life. 'In pain-free survival, another secondary endpoint — which really is freedom from progression of pain over time — we see a very distinct difference' (median 15.2 vs 9.1 months, 1-year pain-free survival rate 54.1% vs 45.1%), he reported. 'Pain is a common and debilitating morbidity in patients with advanced pancreatic adenocarcinoma and a predictor of survival. Thus, by mitigating cancer pain, TTFields may preserve the quality of life of patients with LA-PAC, further supporting TTFields' utility as first-line treatment of this disease,' the authors write in the paper. Patients also performed quality-of-life analyses using the EORTC QLQ-C30 questionnaire, along with the pancreatic cancer–specific PAN26 addendum, 'and using these tools, there was an improvement in deterioration of global health status, pain, and digestive problems,' said Picozzi. Most serious adverse events (SAEs), occurring in 53.6% of the TTFields arm and 48% of controls, were related to chemotherapy or the underlying disease, and were not device-related, the authors wrote. The most common SAEs, which were relatively balanced between arms, were sepsis (6.9% TTFields vs 9.5% controls), cholangitis (5.8% vs 3.7%), bile duct obstruction (5.5% vs 3.3%), and pneumonia (5.1% vs 3.3%), which is a toxicity profile expected for gemcitabine/nab-paclitaxel, Picozzi said. Most device-related AEs were mild-to-moderate skin reactions, consistent with previous trials of TTFields, and could be managed with topical steroids and calcineurin cream. In total, 23 patients (8.4%) had device-related AEs leading to TTFields discontinuation, while discontinuation of chemotherapy due to chemotherapy-related AEs occurred in 17.2% in the TTFields group and 15.8% of controls. Pros and Cons of the Device Study discussant Brian M. Wolpin, MD, a medical oncologist and director of the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Boston, Massachusetts, said, 'Assuming appropriate regulatory approvals, I think the combination of the survival increase and quality-of-life benefits suggests this could be an approach that we could use in patients with locally advanced pancreatic cancer.' But 'there are some lifestyle constraints of wearing the device 18 hours a day continuously for months,' he noted. Wolpin's comments also raised the question of whether TTFields could be combined with other first-line choices for LA-PAC, and pointed out that some oncologists treat locally advanced disease with chemotherapy other than gemcitabine/nab-paclitaxel. 'Many of the newer trials have now started to use multi-agent chemotherapy, many different chemotherapy programs, and different lengths of of these trials have used radiation, some have not,' he said. Indeed, the addition of radiation to first-line chemotherapy for LA-PAC is 'very, very routine' in the United States, Michael Chuong, MD, told Medscape Medical News . Nevertheless, Chuong, a professor of radiation oncology at Florida International University in Miami and medical director of radiation oncology at Miami Cancer Institute, called PANOVA-3's results exciting. 'The use of chemotherapy, plus any other non-chemo treatment, has never before shown a survival difference,' he said. 'For example, randomized trials of chemotherapy, plus or minus definitive radiation therapy, showed only differences in local control. I would say [this trial] definitely is going to lead to this becoming a standard-of-care option now. Whether all patients with locally advanced pancreatic cancer should be getting this remains to be seen.' He said the trial's ad hoc finding of statistically significant benefit for TTFields in distant PFS — but not local PFS — suggests that TTFields may be most effective at delaying metastasis. 'If it's delaying onset of liver and peritoneal disease, which almost every one of these patients will ultimately develop, that's huge,' he said, adding that the trial's high number of participants with CA 19-9 levels greater than 1000 suggested a certain amount of metastatic disease in the cohort. Other TTFields Research Is Ongoing Chuong is conducting a single-arm, phase 2 study in the same type of population. In his study, TTFields is being combined with stereotactic ablative body radiation (SABR) in the first-line setting, and he has hypothesized that this will delay metastasis. 'From a mechanistic standpoint, this is a treatment that's applied to the entirety of the abdomen. These low electrical fields are delivered to the peritoneum, into the liver, and that's where the predominant site of distant metastatic disease is in these patients.' The study was funded by Novocure GmbH. Picozzi disclosed stock and other ownership interests in Amgen, Cigna, Iovance Biotherapeutics, Johnson & Johnson, Lilly, McKesson, and Thermo Fisher; a scientific consulting or advisory role with Revolution Medicines, TriSalus Life Sciences; and research funding from AbbVie, Amal Therapeutics, Astellas Pharma, FibroGen, Ipsen, and NovoCureBrian. Wolpin disclosed a consulting or advisory role with Agenus, BeiGene, EcoR1 Capital, Harbinger Health, Ipsen, Mirati Therapeutics, Revolution Medicines, Tango Therapeutics, and Third Rock Ventures; and research funding from Amgen (Inst), AstraZeneca (Inst), Harbinger Health (Inst), Lilly (Inst), Novartis (Inst), and Revolution Medicines (Inst). Chuong disclosed funding from Novocure, Viewray, and Stratpharma.
