A combination of immunotherapy and targeted therapy has shown promising results in improving overall survival for patients with anaplastic thyroid carcinoma (ATC), a rare and aggressive cancer with a historically poor prognosis. The phase II trial, led by researchers at The University of Texas MD Anderson Cancer Center, combined anti-PD-L1 immunotherapy with mutation-directed targeted therapies, offering a potential new standard of care for patients with specific genetic mutations.
The study, published in JAMA Oncology, enrolled patients with ATC across three cohorts based on their tumor's genetic mutations. Cohort 1 included patients with BRAF-mutated ATC who received atezolizumab plus vemurafenib and cobimetinib. Cohort 2 consisted of patients with RAS-mutated (NRAS, KRAS, or HRAS) or NF1/2-mutated ATC who received atezolizumab plus cobimetinib. Cohort 3 included patients with no mutations who received atezolizumab plus bevacizumab.
Survival Outcomes
The median overall survival across all three cohorts was 19 months, significantly higher than the historical overall survival of 5 months for this patient population. Notably, patients with BRAF V600E mutations in cohort 1 experienced the longest overall survival, with a median of 43.2 months. Objective response rates were 50%, 14%, and 33% in cohorts 1, 2, and 3, respectively.
Addressing Enrollment Challenges
Historically, enrolling patients with ATC in clinical trials has been challenging due to the rarity and aggressive nature of the disease. The study overcame this hurdle by implementing more permissive entry criteria, such as allowing patients to continue chemotherapy during screening and enabling the administration of oral drugs through feeding tubes using alternative formulations.
Safety Profile
The observed side effects were consistent with those reported in previous trials involving these drugs. The most common adverse events across all three cohorts included fatigue, lymphopenia, diarrhea, and anemia. Serious side effects, such as colonic and esophageal perforations, were reported in a few patients.
Expert Commentary
"Patients with anaplastic thyroid carcinoma need treatments that work fast, and we saw promising results with this combination treatment approach," said lead study author Maria Cabanillas, MD, Professor of Endocrine Neoplasia & Hormonal Disorders at The University of Texas MD Anderson Cancer Center. "The takeaway from this study is that immunotherapy really does add benefit for patients."
Study Limitations and Future Directions
The study's limitations include the absence of a control arm, a common challenge in rare tumor trials. Additionally, the acceptance of radiation therapy and surgery to remove the primary tumor may have contributed to the improved survival outcomes. However, the researchers suggest that future ATC clinical trials should be designed to allow for surgery, given its potential impact on survival.
Dr. Cabanillas added, "There are no approved and effective therapies for [anaplastic thyroid carcinoma] with non- BRAF mutations, and we continue to focus our research in that area. We are working to optimize outcomes for our patients. We want them to live longer and better lives, and this study offers hope for patients with [anaplastic thyroid carcinoma]."
