‘Practice-changing’ radioligand therapy may ‘redefine’ treatment of neuroendocrine tumors
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Key takeaways:
- Median PFS improved by more than 1 year for patients who received radioligand therapy.
- ORR improved by more than 30% for patients who received radioligand therapy.
Adding radioligand therapy to first-line treatment of grade 2 or grade 3 gastroenteropancreatic neuroendocrine tumors conferred a significant reduction in risk for disease progression or death, results of a randomized study showed.
Adults who received the radioligand therapy lutetium Lu 177 dotatate (Lutathera, Novartis) had 30% higher overall response rate than the study’s control group, according to findings at ASCO Gastrointestinal Cancers Symposium.
“These positive results for Lutathera are practice-changing and offer new first-line treatment data for patients who have a significant unmet need,” Simron Singh, MD, MPH, FRCPC, co-founder of the Susan Leslie Clinic for Neuroendocrine Tumours at Sunnybrook Health Sciences Centre in Toronto, said in a Novartis-issued press release.
“This study confirms the clinical benefit of first-line radioligand therapy for newly diagnosed patients living with these types of advanced [gastroenteropancreatic neuroendocrine tumors (GEP-NETs)],” Singh added. “These findings should instill confidence among physicians in using Lutathera as a first-line treatment for patients with this life-threatening type of cancer.”
Background and methodology
Between 20% to 30% of well-differentiated GEP-NETs are diagnosed as grade 2 or grade 3, according to background information provided by ASCO.
The incidence of GEP-NETs has risen substantially over the last few decades as well.
Despite this trend, standard first-line treatments have not been established for these patient populations. Instead, clinicians use “consensus guidelines with little supporting evidence,” Singh said in an ASCO-issued press release.
Radioligand therapy specifically targets cancer cells with radiation, binding to receptors on the malignant cells, thus limiting the impact on the surrounding healthy cells.
To be eligible for the trial, patients had to be diagnosed with somatostatin receptor-positive high-grade 2 or grade 3 advanced GEP-NETs (Ki-67 between 10% and 55%) within 6 months of enrollment.
Researchers randomly assigned patients in a 2:1 ratio to receive four cycles of 7.4 gigabecquerel (GBq) lutetium Lu 177 dotatate plus 30 mg of long-acting release (LAR) octreotide long-acting release at 8-weekly intervals or to the study’s control group, who received a higher-dose LAR octreotide (60 mg) every 4 weeks.
PFS served as the study’s primary efficacy end point. Key secondary end points included ORR and quality-of-life assessments.
Results
The trial population included 226 patients (median age 61 years; 53.5% men; 73% white), with 151 in the radioligand therapy cohort and 75 in the control group.
Most of the tumors began in the pancreas (54.4%) or small intestine (29.2%), and 35% of patients had grade 3 tumors.
Patients in the lutetium Lu 177 dotatate cohort had significantly improved median PFS vs. the control group (22.8 months vs. 8.5 months; stratified HR = 0.276; 95% CI, 0.182-0.418) and ORR (43% vs. 9.3%; stratified OR = 7.81; 95% CI, 3.32-18.4). The investigational arm had eight complete responses vs. none for the control group.
“This is [one] of the highest response rates that [has] been reported in neuroendocrine malignancies to date,” Singh said during his presentation at the ASCO symposium.
In the lutetium Lu 177 dotatate arm, 88% of patients received all four cycles of the treatment.
Common adverse events for patients who received lutetium Lu 177 dotatate vs. the control group included nausea (27.2% vs. 17.8%), diarrhea (25.9% vs. 34.2%) and abdominal pain (17.7% vs. 27.4%).
Serious adverse events (grade 3 and above) occurred more frequently in the treatment and included decreased lymphocyte count (5.4%), increased gamma-glutamyltransferase (4.8%), small intestine obstruction (3.4%) and abdominal pain (2.7%). Additionally, investigators reported a secondary hematologic malignancy during the study.
“This first phase 3 study evaluating radioligand therapy in this context could redefine first-line treatments for patients with these complex tumors, filling a critical gap in evidence-based care for patients with advanced grade 2 and 3 gastroenteropancreatic neuroendocrine tumors,” Cathy Eng, MD, FACP, FASCO, ASCO expert and professor of medicine in the department of hematology and oncology at Vanderbilt-Ingram Cancer Center, said in the ASCO press release.
References:
- ASCO. NETTER-2 study: [177Lu]Lu-dotatate shows promise in treating advanced gastroenteropancreatic neuroendocrine tumors (press release). Available at: https://old-prod.asco.org/about-asco/press-center/news-releases/netter-2-study-177lulu-dota-tate-shows-promise-treating. Published Jan. 19, 2024. Accessed Jan. 24, 2024.
- Novartis. Novartis Lutathera significantly reduced risk of disease progression or death by 72% as first-line treatment for patients with advanced gastroenteropancreatic neuroendocrine tumors (press release). Available at: https://www.novartis.com/news/media-releases/novartis-lutathera-significantly-reduced-risk-disease-progression-or-death-72-first-line-treatment-patients-advanced-gastroenteropancreatic-neuroendocrine-tumors. Published Jan. 19, 2024. Accessed Jan. 24, 2024.
- Singh S, et al. Abstract LBA588. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 18-20, 2024; San Francisco.
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Singh S, et al. Abstract LBA588. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 18-20, 2024; San Francisco.
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