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Clinical Trial Shows Promising Results For Patients With Advanced Neuroendocrine Tumors

The Alliance for Clinical Trials in Oncology today announced that an independent Data and Safety Monitoring Board (DSMB) determined that the phase III CABINET (A021602) pivotal trial met its primary endpoint at an interim analysis in both of the trial's cohorts, demonstrating statistically significant and clinically meaningful improvements in progression-free survival (PFS).

CABINET is evaluating cabozantinib compared with placebo in patients with either advanced pancreatic neuroendocrine tumors (pNET) or advanced extra-pancreatic neuroendocrine tumors (also referred to as carcinoid tumors) who experienced progression after prior systemic therapy. The DSMB recommended the study stop early due to efficacy and findings will be discussed with the U.S. Food and Drug Administration. Detailed results from the trial will be presented at an upcoming scientific meeting.

"Patients with progressive neuroendocrine tumors have limited treatment options. At present, after progression on previous therapies, the treatment path is unclear, underscoring the need for additional options for this disease that is rising in incidence," said Jennifer Chan, MD, MPH, study chair for the CABINET trial and Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute.

"These promising findings from the CABINET trial, in which cabozantinib showed an efficacy benefit for patients with pancreatic and extra-pancreatic neuroendocrine tumors, are welcome news and show the potential for cabozantinib to address important unmet needs for this community."

The safety profile of cabozantinib observed in the trial was consistent with its known safety profile, and no new safety signals were identified.

"The Alliance and NCTN have a long and established history of successful practice changing cancer clinical trials. The results of CABINET add to this important work to further improve the outcomes of patients with the rare tumors of pancreatic and extra-pancreatic NET," said Suzanne George, MD, Interim Group Chair of the Alliance, Associate Professor of Medicine at Harvard Medical School and Clinical Director at the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute.

CABINET (Randomized, double-blinded phase III study of cabozantinib versus placebo in patients with advanced neuroendocrine tumors after progression on prior therapy) is a multicenter, randomized, double-blinded, placebo-controlled phase III pivotal trial that enrolled 290 patients in two separate cohorts (pNET, n=93; extra-pancreatic NET, n=197) in the United States.

Patients were randomized 2:1 into the cabozantinib or placebo arms of the study in each of the two cohorts. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression after at least one FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint was PFS in each cohort. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Secondary endpoints included overall survival, radiographic response rate and safety.

"The CABINET trial is a great example of the importance of the National Clinical Trials Network, sponsored by the National Cancer Institute, in conducting rigorous, practice changing trials at both academic and community oncology practices throughout the United States, working with industry partners, patient advocacy, and academia," noted Eileen O'Reilly, MD, from Memorial Sloan Kettering Cancer Center and Jeffrey Meyerhardt, MD, MPH, from Dana-Farber Cancer Institute, who co-chair the Gastrointestinal Committee for the Alliance.

Each year, about 12,000 people will be diagnosed with neuroendocrine tumors. These tumors are cancers that develop from cells in the diffuse neuroendocrine system. The cells can be found throughout the body, but the most common places for tumors to develop are in the gastrointestinal tract, lungs, and pancreas. Most NETs grow slowly, but some are more aggressive, growing rapidly and spreading to other parts of the body. There are several types of treatment for neuroendocrine cancer, including surgery, liver-directed therapy, somatostatin analogs, chemotherapy, targeted therapy, and peptide receptor radionuclide therapy.

"This is great news for patients with advanced neuroendocrine tumors! You will now have another weapon in your arsenal against these cancers," said Julie Krause, a GI patient advocate with the Alliance. "If you are progressing on standard care for treatment of pancreatic and extra-pancreatic neuroendocrine tumors, cabozantinib showed amazing results in the CABINET trial. I am very excited about this advance for these patients."

Provided by Alliance for Clinical Trials in Oncology

Citation: Clinical trial shows promising results for patients with advanced neuroendocrine tumors (2023, August 24) retrieved 31 August 2023 from https://medicalxpress.Com/news/2023-08-clinical-trial-results-patients-advanced.Html

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What To Know About Esophageal Cancer

In the early stages of esophageal cancer, you might not experience any symptoms. However, as the cancer progresses, you may experience symptoms like vomiting, frequent choking while eating, or chronic cough.

The esophagus is a hollow muscular tube that's responsible for moving food from the throat to the stomach. Esophageal cancer can occur when a malignant tumor forms in the lining of the esophagus.

As the tumor grows, it can affect the deep tissues and muscle of the esophagus. A tumor can appear anywhere along the length of the esophagus, including where the esophagus and the stomach meet.

During the early stages of esophageal cancer, there may be no symptoms.

As cancer progresses, a person may notice:

  • difficulty or pain when swallowing
  • chest pain
  • unexpected weight loss
  • persistent cough
  • a hoarse voice
  • vomiting
  • bleeding in the esophagus, which may lead to black stools
  • fatigue due to anemia, which can result from bleeding
  • bone pain and other symptoms, if cancer spreads to other parts of the body
  • indigestion and heartburn
  • a lump under the skin
  • The cause of esophageal cancer isn't yet known, but it involves changes in the DNA of cells related to the esophagus.

    These changes signal the cells to multiply more rapidly than normal cells and disrupt the signal for these cells to die when they should.

    This causes cells to accumulate and become tumors.

    Are there different types of esophageal cancer?

    Testing methods for diagnosing esophageal cancer include the following:

  • An endoscopy involves the use of an instrument with a camera attached to a tube that goes down your throat and allows your doctor to view the lining of your esophagus to check for abnormalities and irritation.
  • A barium swallow is an X-ray imaging test that allows your doctor to see the lining of your esophagus. To do this, you swallow a chemical called barium while the images are being obtained.
  • A biopsy is a process in which your doctor removes a sample of the suspicious tissue with the help of an endoscope and sends it to a lab for testing.
  • A CT scan, PET scan, or MRI may be used to see if cancer has spread to other parts of the body.
  • Around half of all people who receive a diagnosis of esophageal cancer will do so when cancer has already spread beyond the esophagus.

    How do doctors diagnose esophageal cancer?

    Treatments for esophageal cancer will depend on the stage and other factors. Options include surgery, chemotherapy, and radiation therapy.

    Surgery

    If the cancer is small and hasn't spread, a surgeon can remove the tumor using a minimally invasive approach. This will involve an endoscope and several small incisions.

    They may also operate through a larger incision to remove a portion of the esophagus and sometimes the lymph nodes around it. They will reconstruct the tube with tissue from the stomach or large intestine.

    In severe cases, a surgeon may also need to remove a portion of the top of the stomach.

    Chemotherapy

    Chemotherapy involves the use of drugs to attack cancer cells. Chemotherapy may be used before or after surgery. It sometimes accompanies the use of radiation therapy.

    Radiation therapy

    Radiation therapy uses beams of radiation to kill cancer cells. Doctors may combine it with other treatments.

    There are two ways to deliver radiation.

    External delivery is by using a machine. Otherwise, a health professional can place a device near the tumor in a procedure known as brachytherapy.

    Other treatments

    If a tumor obstructs the esophagus, a doctor may implant a small tube called a stent into the esophagus to keep it open.

    Another option is laser therapy, which involves injecting the tumor with a photosensitive drug that attacks the tumor when exposed to light.

    Although there's no sure way to prevent esophageal cancer, some steps can help lower the risk.

    For instance:

  • Avoid smoking and tobacco use.
  • Limit alcohol consumption.
  • Seek treatment for GERD.
  • If a doctor recommends it, taking medications that may help lower the risk, such as nonsteroidal anti-inflammatory drugs.
  • Following a healthy lifestyle with a varied diet and regular exercise.
  • What is the life expectancy for esophageal cancer?

    This will depend on the stage at diagnosis and various individual factors, such as a person's age and how their body responds to treatment. Overall, a person with a diagnosis of esophageal cancer has a 21% chance of living at least another 5 years compared with someone who does not have this disease.

    What are the signs of esophageal cancer?

    Often, there are no signs in the early stages, but a person may begin to notice they have difficulty swallowing, a persistent cough, and a hoarse voice. They may also have indigestion and heartburn and a lump under the skin.

    Is esophageal cancer curable?

    Esophageal cancer is not usually curable, but treatment can enable a person to live longer and improve their quality of life. People who receive a diagnosis in the early stage, before cancer spreads, have a 47% chance of living another 5 years or more after their diagnosis, compared with someone who does not have esophageal cancer.

    Esophageal cancer affects the tube that carries the food from the throat to the stomach. There may be no symptoms at first, but in time a person may develop a cough, a hoarse voice, heartburn, and other symptoms.

    Treatment is available to manage esophageal cancer. The options will depend on the stage of cancer and other factors. They include surgery, radiation therapy, and chemotherapy.






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