A breakthrough treatment in the war against endometrial cancer has made significant progress – showing promising results in decreasing recurrence and death from a devastating disease – while an experimental vaccine against pancreatic cancer triggered an immune response in nearly 99% of participants, notes MedicalBrief.
In the endometrial cancer phase 3 trial led by researchers from NYU Langone Health and Perlmutter Cancer, a landmark international study looked at the effects of anti-cancer medicine sacituzumab tirumotecan (sac-TMT) compared with standard chemotherapy drugs, reports New York Post.
The results could offer hope for a disease that kills more than 97 000 people around the world each year.
Endometrial cancers are becoming deadlier, yet have few effective treatment options, especially if diagnosed at a later stage.
The study compared sac-TMT to standard chemotherapy drugs for advanced or recurrent endometrial cancer in women who had already been treated with an established PD-1 inhibitor drug that makes cancer cells more visible to immune system attack.
Those treated with the investigational drug had a 41% lower risk of their cancer progressing and spreading to other parts of the body than chemo alone, and a 32% lower overall risk of death.
Meanwhile, 35% of women treated with sac-TMT showed positive responses, including tumour shrinkage, more than twice that of those having standard chemotherapy.
“These positive results …establish this drug as a new standard treatment in recurrent endometrial cancer,” said study principal investigator Bhavana Pothuri.
Sac-TMT is designed to attach to the trophoblast cell-surface antigen 2 (Trop-2) protein that sits on the surface of endometrial cancer cells.
As an antibody-drug conjugate, the new drug is a targeted cancer therapy that delivers more drug to tumour cells while limiting damage to healthy cells.
The treatment wasn’t without side effects, though, with the most frequent ones including low blood counts, inflammation in the mouth and dry or itchy eyes.
Still, the researchers reported all of the adverse effects were manageable.
The positive results of the study also show promise for use of the sac-TMT drug in other cancers with excessive amounts of Trop-2, like lung, breast, ovarian and intestinal tumours.
The research showed similar results to another phase 3 clinical trial conducted by Merck back in May: more than 770 patients with endometrial cancer received either sac-TMT every two weeks or a treatment of the physician’s choice, including doxorubicin or paclitaxel chemotherapy.
Those given sac-TMT showed “clinically meaningful improvement” in their disease state compared with the treatment of the physician’s choice.
While Merck didn’t disclose any statistics on exact survival benefit, response rate, side effect rates or other details, it reported the drug met response rate benchmarks and exhibited similar side effects to earlier studies.
As a result of the Merck clinical trial and the NYU Langone study, Pothuri recommends that “clinical guidelines for endometrial cancer will need to be reassessed to incorporate sacituzumab tirumotecan”.
The TroFuse-005 trial was the first global trial to “demonstrate statistically significant improvement” from sacituzumab tirumotecan compared with chemotherapy, said a Merck press release.
Pancreatic shot
Meanwhile, Medical News Today reports that a group of researchers who conducted a randomised phase 2 trial for a pancreatic cancer vaccine said it triggered an immune response in nearly 99% of participants.
Although the vaccine produced a strong immune response, however, the team didn’t find a statistically significant improvement in disease-free survival, they noted.
While surgery and chemotherapy can treat pancreatic cancer, the cancer cells may remain in the body and cause the cancer to return, and this latest study examined whether the experimental vaccine camupepimut could help reduce this risk in people who had already undergone surgery and chemotherapy.
The findings are published in Nature Medicine.
Pancreatic cancer makes up around 3% of cancer cases per year in the United States, and is one of the most difficult cancers to treat, partly because it often does not have many early warning signs and is not often diagnosed until after it has already spread.
Pancreatic ductal adenocarcinoma (PDAC) is the most common form: it has a high risk of recurrence, even after surgery and chemotherapy.
Mutations in the KRAS gene occur in around 90% of PDAC cases, which can cause cells to grow uncontrollably and contribute to cancer development.
With this in mind, US researchers developed the vaccine camupepimut to target several common KRAS mutations. The jab delivers its components to the lymph nodes, where it helps immune cells recognise cancer cells with KRAS mutations.
The researchers described camupepimut as an “off-the-shelf” treatment that could potentially work for people with several KRAS mutations.
Unlike personalised cancer vaccines, which are developed based on an individual’s tumour, this approach could make the vaccine more widely available.
For the randomised phase 2 AMPLIFY-7P trial, the research team enrolled 144 participants with KRAS-mutated pancreatic cancer (stages 1 to 3). They had surgery and chemotherapy treatment before enrolling.
None showed signs of recurrence on imaging tests when they entered the trial.
The researchers divided participants into two groups:
• vaccine group (96 participants)
• control group (48 participants).
The team focused on disease-free survival, or how long they lived without their cancer returning or dying. They also examined immune responses and treatment safety.
Vaccine boosts immunity, but survival uncertain
The researchers found that the vaccine triggered a strong immune response in nearly everyone in the vaccine group, activating T cells that target KRAS mutations in nearly 99% of the test group. The jab also increased T-cell activity by more than ninefold in 82.2% of those evaluated.
Despite these strong immune responses, the vaccine did not meet the study’s primary endpoint for disease-free survival. The median disease-free survival was 23.8 months in the vaccine group compared with 21.2 months in the observation group.
At six months, 75.7% of the vaccine group remained disease-free, compared with 61.7% of the control group. Although this difference suggested a possible early benefit, it did not reach statistical significance.
The researchers also did not find a statistically significant improvement in disease-free survival over the full follow-up period.
After conducting further analyses, the researchers believe that certain people might benefit more from the vaccine.
For example, participants who had no detectable Circulating tumour DNA (ctDNA) at the start of the trial appeared to experience better disease-free survival after vaccination. Detectable ctDNA can indicate that cancer cells remain in the body after treatment.
The team also observed an association between stronger T-cell responses and longer disease-free survival. The vaccine was generally well-tolerated, with no treatment-related deaths or adverse events.
Lead study author and Mayo Clinic oncologist Ben George, MD, explained that the vaccine group had a higher proportion of patients with detectable ctDNA, which is associated with a greater risk of cancer recurrence.
“After adjusting for imbalances, camupepimut decreased the risk of recurrence or death by 53%,” said George. “This is a strong signal that warrants prospective testing in a phase 3 trial which will be designed to confirm these signals.”
George said that the next trial will need to account for patients’ ctDNA status and examine whether longer vaccination or combination treatments improve outcomes.
Important findings
Anton Bilchik, MD, PhD, surgical oncologist, chief of medicine and Director of the Gastrointestinal and Hepatobiliary Programme at Providence Saint John’s Cancer Institute, who was not involved in the study, told Medical News Today that the findings are “extremely important” despite the lack of a statistically significant survival benefit.
“It shows that a very resistant cancer such as pancreatic cancer is capable of responding to a vaccine, provided the patient develops a strong immune response,” he said.
He noted that the study’s small size and limited vaccination period may have influenced the results.
“We should therefore interpret these results with optimism recognising that more studies need to be done to evaluate the benefit in different subsets of patients and in determining the survival benefit when the vaccine is given for a longer period.”
Jason Williams, MD, founder and director of interventional oncology and immunotherapy at Williams Cancer Institute, who was also not involved in the study, said that activating the immune system is only part of the challenge.
“Seeing the cancer is the first step,” Williams said. “Clearing it is another.”
He suggested that combining the vaccine with other treatments could help overcome pancreatic cancer’s ability to suppress the immune system.
See more from MedicalBrief archives:
Guided missiles create super highway for targeted cancer treatment
How pancreatic cancer evolves to evade treatment – US study
Cancer jab using immune system’s ‘killer’ cells on the cards – UK study
Small pancreatic cancer vaccine trial shows promise