The theme of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting is Partnering With Patients: The Cornerstone of Cancer Care and Research. From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world will gather to discuss the latest research and how to ensure that all people receive the cancer care they need.
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Some of the notable research that will be presented today includes:
What did this study find: The DESTINY-PanTumor02 study found that trastuzumab deruxtecan (Enhertu) is an effective treatment option for people with difficult-to-treat tumors that express HER2 (human epidermal growth factor 2). HER2 is a protein on a cell that causes cancer to grow.
Although HER2 is expressed in many types of tumors, there are currently no approved HER2-targeted therapies for many types of cancer, especially for some cancers that are hard to treat. Trastuzumab deruxtecan is an antibody-drug conjugate, which is a type of targeted therapy, currently approved for treating breast, stomach, and non-small cell lung cancers that express HER2 or have mutations in HER2.
This international, phase 2 study included 267 people with HER2-expressing, locally advanced or metastatic cancer that had worsened after at least one systemic treatment or that had no treatment options. Each participant received at least one dose of trastuzumab deruxtecan. The people in the study had their tumor tissue tested for the amount of HER2 receptor protein present in cancer cells. This testing is called immunohistochemistry (IHC), and IHC 3+ indicates higher levels of HER2 expression than IHC 2+.
At the median follow-up of 9.7 months, 37.1% of tumors responded to trastuzumab deruxtecan. The median is the midpoint, meaning that half the participants were observed for more than 9.7 months, and the other half were observed for less than that. The median amount of time that tumors continued to respond to treatment was nearly 1 year (11.8 months). In those tumors with IHC 3+, the treatment was even more effective, with 61.3% responding to treatment and a continued treatment response time of 22.1 months. Across different cancer types, the percentage of tumors responding to treatment were:
Biliary tract cancer: 22% for all patients, 56.3% for IHC 3+, 0% for IHC 2+
Bladder cancer: 39% for all patients, 56.3% for IHC 3+, 35% for IHC 2+
Cervical cancer: 50% for all patients, 75% for IHC 3+, 40% for IHC 2+
Ovarian cancer: 45% for all patients, 63.6% for IHC 3+, 36.8% for IHC 2+
Pancreatic cancer: 4% for all patients, 0% for IHC 3+, 5.3% for IHC 2+
Uterine cancer: 57.5% for all patients, 84.6% for IHC 3+, and 47.1% for IHC 2+
More than half (58.4%) of the people in this study experienced side effects. For 11.6% of the participants, side effects led them to stop treatment. The most common treatment-related side effects were nausea, fatigue, and low levels of blood cells (cytopenia).
What does this mean for patients? For people with HER2-expressing solid tumors, trastuzumab deruxtecan could be an effective treatment option.
“HER2 is present in many cancer types, such as breast, gastric, lung, gynecologic, and urothelial cancers, and patients with HER2-expressing, hard-to-treat cancers need new treatment options. These results advance our clinical understanding of HER2 expression, reaffirm HER2 as an actionable biomarker across a broad range of tumor types, and show that trastuzumab deruxtecan could potentially provide a new treatment option for patients with advanced disease across these tumors, especially in patients with HER2 IHC 3+ or 2+ expression.”
— lead study author Funda Meric-Bernstam, MD
University of Texas MD Anderson Cancer Center
Ciltacabtagene autoleucel reduces risk of disease progression by 74% in multiple myeloma after lenalidomide stops working
Who does this study affect: People with multiple myeloma that no longer responds to treatment with lenalidomide (Revlimid).
What did this study find: Results from the global, phase 3 CARTITUDE-4 clinical trial show that ciltacabtagene autoleucel (Carvykti), a chimeric antigen receptor (CAR) T-cell therapy, slows or stops the progression of multiple myeloma when compared with standard-of-care treatments after lenalidomide no longer works.
Multiple myeloma is a blood cancer of cells in the bone marrow, specifically the immune cells called plasma cells. A medication called lenalidomide (Revlimid) is regularly used to treat multiple myeloma. It is an immunomodulatory drug that stimulates the immune system. However, lenalidomide will eventually stop working for approximately 50% to 80% of people with multiple myeloma. When lenalidomide stops working, combinations of different medications are used. In the CARTITUDE-4 study, the researchers wanted to see if using ciltacabtagene autoleucel sooner after lenalidomide stopped working was more effective than the current standard treatment combinations.
Ciltacabtagene autoleucel is a CAR T-cell therapy. It is already approved by the U.S. Food and Drug Administration to treat multiple myeloma after at least 4 previous lines of therapy. In CAR T-cell therapy, some T cells are removed from a patient’s blood. Then, the cells are changed so they have specific proteins called receptors. The receptors allow the changed T cells to recognize the cancer cells. For ciltacabtagene autoleucel, the changed cells recognize the BCMA protein. The changed T cells are then returned to the patient’s body to seek out and destroy cancer cells. (Learn more about the basics of CAR T-cell therapy.)
The study included 419 people from 16 countries across the world who had already received 1 to 3 lines of treatment for multiple myeloma, including lenalidomide (Revlimid), which was no longer working. The study participants were around 61 years of age, 55% were men, and 75% were White. They were divided into 2 groups, with 208 participants receiving ciltacabtagene autoleucel and 211 participants receiving standard-of-care treatment, which is either a combination of bortezomib (Velcade), pomalidomide (Pomalyst), and dexamethasone or a combination of daratumumab (Darzalex), pomalidomide, and dexamethasone.
The participants were followed for a median of 16 months. The median is the midpoint, meaning half the patients were followed for less than 16 months and the other half were followed for longer. The researchers found that ciltacabtagene autoleucel reduced the risk of disease progression by 74%, compared with the standard-of-care treatments. The objective response rate, which is the percentage of patients whose tumors responded to the treatment, was 84.6% in the group treated with ciltacabtagene autoleucel, compared with 67.3% in the group that received standard-of-care treatment. Those receiving the CAR T-cell therapy also had better minimal residual disease negativity (60.6%), compared with those receiving standard of care (15.6%). Minimal residual disease negativity indicates the percentage of patients for whom testing did not find any remaining cancer cells after treatment.
Most participants (97% receiving ciltacabtagene and 94% receiving standard of care) experienced side effects. The most common side effects were infections (27% vs. 25%) and low blood cell counts (94% vs. 86%), including neutropenia, thrombocytopenia, and anemia. Cytokine release syndrome, which may arise as immune cells are sent into overdrive by the treatment, developed in 76% of participants who received ciltacabtagene autoleucel. Around 5% of those receiving the CAR T-cell therapy developed immune effector cell-associated neurotoxicity syndrome (ICANS), a syndrome that affects a person’s nervous system. (Learn more about the side effects of immunotherapy.)
What does this mean for patients? When multiple myeloma no longer responds to lenalidomide, ciltacabtagene autoleucel may be an effective treatment to use soon afterward.
“Lenalidomide-based therapies are used extensively as frontline treatments, in both young and elderly patients and including those who are transplant-eligible and transplant-ineligible. This causes an increase in the number of cases where the disease no longer responds to lenalidomide early in the course of the disease. These findings show that ciltacabtagene autoleucel is highly effective in patients with lenalidomide-refractory multiple myeloma as early as after first relapse.”
— lead study author Binod Dhakal, MD
Medical College of Wisconsin
Visit the Cancer.Net Blog each day of the meeting for more scientific highlights from the 2023 ASCO Annual Meeting and how the new research will affect patient care. You can also keep up with the meeting’s news by following Cancer.Net on Facebook and Twitter, where you can follow the #ASCO23 hashtag.
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