The first randomized study in patients with malignant pheochromocytoma and paraganglioma has found that sunitinib prolongs progression-free survival by more than 5 months. The late-breaking results of the FIRSTMAPPP trial were presented by Eric Baudin, MD, PhD, and colleagues at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract 567O_PR).
Eric Baudin, MD, PhD
“This trial provides the highest level of evidence ever reached in this very rare cancer,” said Dr. Baudin, Chair of Neuroendocrine Tumors at Gustave Roussy. “The results are practice-changing. Sunitinib is a new option for these patients and becomes the therapy with the most robust indication of antitumor activity in progressive malignant pheochromocytoma and paraganglioma. Based on these findings, new recommendations may consider sunitinib as the first-line therapy in patients with this condition.”
FIRSTMAPP Details and Findings
Malignant pheochromocytoma and paraganglioma is a very rare neuroendocrine tumor, with an annual incidence of less than 1 per million. During an 8-year period, FIRSTMAPPP enrolled 78 patients with progressive malignant pheochromocytoma and paraganglioma from 15 centers in four European countries. The average age was 53 years, and 59% of participants were men. Participants were randomly assigned to receive sunitinib or placebo. The primary endpoint of progression-free survival at 12 months was achieved by 35.9% of patients in the sunitinib group, meaning that 14 out of 39 patients experienced no progression of their tumor for at least 1 year. The progression-free survival rate in the placebo group was 18.9%. The median progression-free survival was 8.9 vs 3.6 months in the sunitinib and placebo groups, respectively.
Juan W. Valle, MD, PhD
“This is a strong result, showing that the 12-month progression-free survival rate with sunitinib was nearly double that seen with placebo,” commented Juan W. Valle, MD, PhD, of the University of Manchester and The Christie NHS Foundation Trust. “None of the treatment options we currently have for advanced malignant pheochromocytoma and paraganglioma are supported by randomized clinical trial evidence. This disease is commonly treated using combined chemotherapy with cyclophosphamide, vincristine, and dacarbazine, all quite old agents and all very toxic. Sunitinib will be much better tolerated.”
In the trial, severe adverse events occurred in 54% patients in the sunitinib group vs 49% in the placebo group, the most frequent being asthenia/fatigue (18% vs 3%) and hypertension (10% vs 6%). One death occurred in each arm.
Dr. Baudin said, “The study demonstrated that sunitinib at 37.5 mg per day was tolerable. In particular, we know that two-thirds of patients with malignant pheochromocytoma and paraganglioma have hypertension due to high levels of hormones, yet hypertension induced by the drug was manageable.”
Dr. Valle concluded, “This study confirms the ability of trials to answer efficacy questions in patients with rare cancers. It also highlights the crucial role of widespread collaboration in academic studies. We know that to access these treatments, patients need to be managed through expert centers. We must facilitate this if we are to ensure that patients are given the opportunity to receive these treatments and to be enrolled in the next generation of clinical trials for new therapies.”
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.