Archive for category: News

Tocolytic medications are commonly used to delay preterm birth. Atosiban, an oxytocin receptor antagonist, is one such tocolytic used for threatened preterm labor. However, the effect of atosiban on improving neonatal outcomes remains unclear. This randomized controlled trial aimed to determine whether atosiban is superior to placebo in reducing morbidity in women with threatened preterm birth between 30+0 and 33+6 weeks of gestation. The primary outcome was a composite of perinatal mortality and neonatal morbidity, while key secondary outcome was the occurrence of adverse maternal events. According to study results, there was no significant difference in neonatal outcomes between atosiban and placebo. Although this study was well done, it was limited by a low event rate, which may decrease the ability to detect smaller differences between groups.

This was an international, multicentre, randomised, double-blind, superiority trial conducted in 26 hospitals in the Netherlands, England, and Ireland. After written informed consent, women aged 18 years or older with a singleton or twin pregnancy with threatened preterm birth from 30+0 to 33+6 weeks of gestation were randomly assigned (stratified by centre, 1:1 ratio) to intravenous atosiban or placebo. The primary outcome was a composite of perinatal mortality (stillbirth and death until 28 days postpartum) and six severe neonatal morbidities. Analysis was by intention-to-treat. Treatment effect was estimated as relative risk (RR) with 95% CI. This trial was prospectively registered at EudraCT (2017-001007-72) and the Netherlands Trial Registry (NL-OMON54673), and is complete. Findings: Between Dec 4, 2017, and July 24, 2023, a total of 755 participants were randomly assigned, of whom 752 were included in the intention-to-treat analysis (atosiban n=375, placebo n=377). The primary outcome occurred in 37 (8%) of 449 infants in the atosiban group and 40 (9%) of 435 in the placebo group (RR 0·90 [95% CI 0·58–1·40]). There were three (0·7%) and four (0·9%) infants who died, respectively (RR 0·73 [0·16–3·23]); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups, and there were no maternal deaths. They did not demonstrate superiority of atosiban over placebo in improving neonatal outcomes as treatment for threatened preterm birth from 30+0 to 33+6 weeks of gestation. As the primary goal of tocolysis should be improvement of neonatal outcomes, our outcomes question the standardised use of atosiban as treatment for threatened preterm birth from 30+0 to 33+6 weeks of gestation. The findings should reduce practice variation across countries and will contribute to evidence-based treatment for patients with threatened preterm birth.

The FDA has granted accelerated approval to the combination therapy of avutometinib and defactinib (Avmapki Fakzynja Co-pack) for adults with KRAS-mutated, recurrent low-grade serous ovarian cancer who have previously undergone systemic therapy. This marks the first approved treatment specifically for this patient population, according to Verastem Oncology.

This indication is approved under accelerated approval based on the tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. AVMAPKI plus FAKZYNJA is only commercially available in the U.S. as an oral combination co-pack with the two prescription products, known as “AVMAPKI FAKZYNJA CO-PACK.”

“Today’s approval of AVMAPKI FAKZYNJA CO-PACK for patients with KRAS-mutated recurrent low-grade serous ovarian cancer represents not only the first-ever FDA-approved treatment specifically for this rare cancer but also a new day for people living with this disease who have been in desperate need of new treatment options,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “We are very proud to bring two innovative medicines in one combination treatment to the LGSOC community. We thank the researchers, patients, and their families participating in our clinical trials, the patient advocacy community, the FDA, and everyone at Verastem for their dedication and commitment to helping us bring AVMAPKI FAKZYNJA CO-PACK to patients in the U.S.”

The accelerated approval of AVMAPKI FAKZYNJA CO-PACK is based on the Phase 2 RAMP 201 clinical trial, which evaluated the combination of AVMAPKI and FAKZYNJA in adult patients with measurable KRAS-mutated recurrent LGSOC.

“Low-grade serous ovarian cancer is a rare and highly recurrent cancer with limited effective treatment options. This first-ever FDA approval in this disease was based on the primary analysis of the Phase 2 RAMP 201 trial, in which the combination of avutometinib and defactinib resulted in a significant overall response rate for patients with a KRAS mutation while being generally well tolerated,” said Rachel Grisham, M.D., Section Head, Ovarian Cancer at Memorial Sloan Kettering Cancer Center in New York, NY and Global Lead Principal Investigator of GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301. “The approval of avutometinib plus defactinib brings a much-needed therapeutic option to patients and establishes this combination as the new standard of care for women with recurrent low-grade serous ovarian cancer harboring a KRAS mutation. I look forward to progressing the confirmatory Phase 3 trial, RAMP 301, where we look to continue to support the ongoing body of research of this combination in women with and without a KRAS mutation.”

“To see our early research in both the FRAME and RAMP 201 trial in recurrent low-grade serous ovarian cancer advance the combination of avutometinib and defactinib to now be the first-ever FDA-approved therapy for this disease is what gives us real hope when treating patients with rare or difficult-to-treat gynecological cancers,” said Professor Susana Banerjee, M.B.B.S., M.A., Ph.D., F.R.C.P, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London and Global Lead Principal Investigator of ENGOTov60/GOG3052 /NCRI/RAMP201. “With this approval, we thank all of the patients and researchers who participated in this trial, and the low-grade serous ovarian cancer community for their contributions to help bring the first FDA-approved treatment for KRAS-mutated recurrent LSGOC and changing the treatment possibilities for RAS/MAPK-pathway-driven cancers. We now need to build on this milestone to bring this new treatment to patients around the world.”

Prior to this approval, there were no FDA-approved treatments specifically for KRAS-mutated recurrent LGSOC, a rare and distinct ovarian cancer that differs from high-grade serous ovarian cancer in both its biology and how it responds to treatment.

“One of the most devastating aspects of my LGSOC diagnosis was learning there are no FDA-approved treatments for this rare cancer. While there were some treatment options at the time that I could try, I made it my mission to advocate for research specific to my disease,” said Nicole Andrews, chair of the STAAR Low-Grade Serous Ovarian Cancer Foundation. “Today we’re celebrating a milestone with the first-ever FDA-approved treatment option specifically for patients with recurrent LGSOC with a KRAS mutation. The low-grade serous ovarian cancer community is hopeful and excited about the potential benefits of this treatment and the progress toward improving the diagnosis, awareness, and research for LGSOC.”

AVMAPKI FAKZYNJA CO-PACK is the first treatment to receive regulatory approval anywhere in the world, specifically for KRAS-mutated recurrent LGSOC. The Company believes AVMAPKI FAKZYNJA CO-PACK is also the first-ever oral, novel/novel combination therapy approved in oncology. Verastem initiated a rolling new drug application (NDA) with the FDA in May 2024 and completed its NDA submission in October 2024. The FDA granted Priority Review, and the approval was received in advance of its Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025. The FDA granted Breakthrough Therapy Designation for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy, in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

The AVMAPKI FAKZYNJA CO-PACK is expected to be available for adult patients with KRAS-mutated recurrent LGSOC in the U.S. in one week.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a rare ovarian cancer that is insidious and persistent. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. Approximately 70 percent of LGSOC shows RAS pathway-associated mutations, and 30 percent of people with LGSOC have a KRAS mutation. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life. The current standard of care for LGSOC includes hormone therapy and chemotherapy.

About AVMAPKI and FAKZYNJA Combination Therapy

AVMAPKI (avutometinib) inhibits MEK kinase activity while also blocking the compensatory reactivation of MEK by upstream RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway. Blocking RAF and/or MEK activates FAK, a key mediator of drug resistance. FAKZYNJA (defactinib) is a FAK inhibitor and together, the avutometinib and defactinib combination was designed to provide a more complete blockade of the signaling that drives the growth and drug resistance of RAS/MAPK pathway-dependent tumors.

Additional clinical investigations: Verastem Oncology is conducting clinical trials with avutometinib with and without defactinib in RAS/MAPK-driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (GOG-3097/ENGOT-ov81/GTG-UK) (NCT06072781), is an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) with and without a KRAS mutation.

RAMP 203 (NCT05074810) is a Phase 1/2, multicenter, open-label, dose evaluation/expansion study, being conducted in collaboration with Amgen, evaluating the efficacy and safety of avutometinib and sotorasib with or without defactinib in patients with KRAS G12C mutant non-small cell lung cancer (NSCLC) who have not been previously treated with a KRAS G12C inhibitor as well as in patients who have been previously treated with a KRAS G12C inhibitor (NCT05074810). RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award. Avutometinib and defactinib are not approved by the FDA or any other regulatory authority, either in combination or with other therapies, for any of these investigative uses. Neither avutometinib nor defactinib are approved by the FDA or any other regulatory authority on a stand-alone basis for any use.

Exercise can counter the detrimental effects of cancer treatment, such as heart and nerve damage and brain fog, suggests an overarching review of the existing pooled data analyses of the most recent research, published online in the British Journal of Sports Medicine.

Exercise also seems to boost psychological wellbeing and overall quality of life, lending weight to its routine inclusion in treatment protocols for the disease, say the researchers.

Several pooled data analyses of the available research have evaluated the impact of exercise on health outcomes in people with cancer, but significant gaps remain in our understanding, explain the researchers.

And to date, no comprehensive evaluation of the results of existing pooled data analyses on exercise and health outcomes in people with a broad range of cancers has been published, they add.

To plug this gap, with the aim of strengthening the evidence base and informing clinical care, the researchers carried out an umbrella review of the existing pooled data analyses of randomised controlled trial results, published between 2012 and July 2024.

The review included 485 associations from 80 articles, all evaluated as being of moderate to high quality.

Among these associations, the types of exercise of any length, intensity, and duration included mind–body (138, 28.5%), such as Qigong, tai-chi, and yoga; aerobic and resistance exercise (48,10%), high intensity interval training (HIIT) (18,4%); and other types (281,59%).

These associations were explored in people with cancers of the breast (244, 50%), digestive system (20,4%), blood (13, 3%), lung (47,10%), prostate (12, 2.5%) plus others (149, 31%).

In all, 260 (54%) associations were statistically significant, and 81 (17%) and 152 (31%), respectively, were supported by high and moderate certainty evidence, according to GRADE criteria—used to assess the certainty of scientific evidence and the strength of recommendations in health care.

Exercise significantly reduced various side effects associated with cancer and its treatment compared with usual care or no exercise. For example, it lessened heart and peripheral nerve damage associated with chemotherapy, brain fog (cognitive impairment), and shortness of breath (dyspnoea).

It also changed body composition and key physiological indicators of health, such as insulin, insulin-like growth factor, and C-reactive protein in people with cancer. And it improved sleep quality, psychological wellbeing, the normal workings of the body, and social interaction, while boosting overall quality of life.

And there was evidence of high to moderate certainty that preoperative exercise reduced the risk of postoperative complications, pain, length of hospital stay, and risk of death.

The researchers acknowledge various limitations to their findings. The pooled data analyses included in the review differed considerably, including the number of studies on which they variously drew.

Participants with cancer able to exercise might also have been healthier, the researchers suggest. And side effects of treatment vary, depending on cancer type and how advanced the disease is, they point out.

But they conclude: “Incorporating mind–body exercises into the exercise guidelines for people with cancer may be a valuable consideration. Future high quality research is needed to explore additional outcomes, clarify underlying mechanisms and refine exercise prescriptions tailored to cancer type, treatment timing, exercise modality and individual characteristics, ensuring more precise and clinically relevant interventions for diverse cancer populations.”

Reference:

https://bjsm.bmj.com/lookup/doi/10.1136/bjsports-2024-109392

Women are around 50% more likely than men to develop COPD, the umbrella term for chronic lung conditions, such as emphysema and bronchitis, even if they have never smoked or smoked much less than their male counterparts, suggests observational research, published in the open access journal BMJ Open Respiratory Research.

A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early stage and amenable to treatment in up to half of cases, suggests a modeling study published in the open access journal BMJ Open.