The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a new program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this new series, cancer care providers will now gather online to learn about new, carefully selected research and discuss the study results with their colleagues.
November 2021 marks the launch of the ASCO Plenary Series. The first session features a study on the treatment of metastatic melanoma and another on using technology to find and treat symptoms early.
Follow the discussion about research from the ASCO Plenary Series by using the #ASCOPlenarySeries hashtag on Twitter.
Combination immunotherapy is more effective than combination targeted therapy for metastatic melanoma
Who does this study affect: People with metastatic melanoma with a BRAF V600 mutation.
What did this study find: Metastatic melanoma with a specific mutation called BRAF V600 often responds to treatment with specific combinations of immunotherapy or targeted therapy. This mutation can be found in nearly half of people with metastatic melanoma. In the DREAMseq study, the researchers wanted to find out which treatment combination was more effective at treating metastatic melanoma with a BRAF V600 mutation.
The immunotherapy combination used to treat this kind of melanoma includes nivolumab (Opdivo) and ipilimumab (Yervoy). These drugs are a specific type of immunotherapy called immune checkpoint inhibitors. Nivolumab blocks a molecule called PD-1, and ipilimumab blocks a molecule called CTLA-4. The targeted therapy combination used in this study is dabrafenib (Tafinlar), which targets the BRAF mutation, and trametinib (Mekinist), which targets the MEK mutation.
There were 265 participants in this study, and they were divided evenly among 2 groups. The 133 people in Group 1 received the immunotherapy combination first. If the treatment did not work and the melanoma continued to grow and spread, then they received the targeted therapy combination. The 132 people in Group 2 received the targeted therapy combination first. If the targeted treatment combination did not work, then they received the immunotherapy combination. All study participants received imaging scans at the beginning of the study and every 12 weeks after that to find out if the disease had been stopped.
After a median follow-up period of nearly 28 months, the researchers found that the immunotherapy combination was more effective than the targeted therapy combination. The median is the midpoint, meaning half of the participants were followed for less than 28 months and the other half were followed for more than 28 months. Among the people in Group 1, 27 moved on to receive the targeted therapy combination. In Group 2, 46 people moved from the targeted therapy combination to receive immunotherapy. For the first treatments given, the melanoma responded at similar rates: 46% for the immunotherapy combination and 43% for the targeted therapy combination. But if participants moved on to the second treatment, the melanoma responded to targeted therapy in 48% of patients and to immunotherapy in 30% of patients. Serious side effects were more common with immunotherapy. Among those who received immunotherapy first, 60% had a serious side effect, compared with 52% among those who received targeted therapy first.
The 2-year overall survival rate for those who started with immunotherapy was 72%. For those who started with targeted therapy, the 2-year overall survival rate was 52%. For a small number of participants, the targeted therapy combination as a first treatment was more effective in the first 10 months, but this effect was temporary and did not last over the long term. The researchers are hoping to find out more about why these patients may have experienced this effect. In addition, the researchers found that the melanoma was less likely to respond to treatment with immunotherapy if it was given after targeted therapy.
What does this mean for patients: For people with metastatic melanoma with a BRAF V600 mutation, beginning treatment with nivolumab and ipilimumab helped more people live longer than starting treatment with dabrafenib and trametinib.
“Our findings establish definitively that even for this oncogene driven tumor that the sequence beginning with immunotherapy—rather than targeted therapy—produces better overall survival for the vast majority of patients. This is practice-changing because many patients, especially in the community oncology setting, receive targeted therapy as their initial treatment.”
—lead study author Michael B. Atkins, MD
Georgetown Lombardi Comprehensive Cancer Center
Who does this study affect: People receiving active treatment for metastatic cancer.
What did this study find: Researchers from the PRO-TECT clinical trial found that having patients fill out online surveys about their symptoms during cancer treatment helped their health care teams find and treat symptoms earlier and improved the patients’ quality of life.
This study was conducted across 52 cancer clinics in the United States and included 1,191 people with metastatic cancer who were receiving systemic treatment with medications. The median age of the participants was 63 years, and more than half (58%) were women. Most of the people in this study were white (80%), and 17% were Black. About 1 of every 4 people (27%) in this study lived in a rural location, and nearly 4 in 10 (39%) reported high school as their highest level of education. There were 201 participants (17%) who had never used the internet before.
The participants were divided into 2 groups. The 593 people in the study group received patient-reported outcome (PRO) surveys that asked about and tracked symptoms. The 598 people in the control group received standard supportive care to find and treat symptoms. For those in the PRO group, participants received a notification every week to fill out a survey describing their current symptoms, such as pain, nausea, vomiting, constipation, and diarrhea, as well as insomnia, depression, falls, and financial problems. The surveys were available in English, Spanish, and Mandarin Chinese. Participants could complete their surveys on a website or through an automated phone system. Reminders and follow-up calls were sent if participants did not submit their surveys for the week.
If the survey results indicated that someone’s symptoms were severe or worsening, they were emailed information about how to manage their symptoms at home. In addition, an email alert was sent to nurses at their treatment centers. The nurses were then able to reach out to the patients and help them manage their symptoms and get additional care, if necessary. The patient’s oncologist also received a report with data about their symptoms.
All study participants were given questionnaires about their symptoms, physical ability, and quality of life at regular intervals for up to 1 year during this study. Compared with the control group, the researchers found that 16% more patients in the PRO group had improved symptom control, 14% more patients in the PRO group had improved physical function, and 13% more patients in the PRO group had improved health-related quality of life. The participants also completed the majority of their weekly surveys, with over 90% of sent surveys receiving a response.
What does this mean for patients: For people in active treatment for metastatic cancer, technology offers potential solutions to help patients report their symptoms to their cancer care team. Detecting and managing symptoms early can help improve the physical condition of people with cancer and lead to a higher quality of life.
“This national trial provides evidence that a simple technology asking patients about their symptoms is feasible, significantly improves symptom management, and yields better clinical outcomes. For this type of system to work, it is essential to have not only high patient participation, but a strong commitment from the health care team.”
—lead study author Ethan Basch, MD, MSc, FASCO
University of North Carolina (UNC) Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina