The first randomized study in malignant pheochromocytoma and paraganglioma (MPP) has found that sunitinib prolongs progression-free survival (PFS) by more than five months. The late breaking results of the FIRSTMAPPP trial are presented at the ESMO Congress 2021.

This trial provides the highest level of evidence ever reached in this very rare cancer. 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."

Dr. Eric Baudin, Study Author, Chair, Neuro-Endocrine Tumours, Gustave Roussy – Cancer Campus, Villejuif, France

MPP is a very rare neuroendocrine tumor, with an annual incidence of less than one per million. During an eight-year period, FIRSTMAPPP enrolled 78 patients with progressive MPP from 15 centers in four European countries. The average age was 53 years and 59% were men. Participants were randomly allocated to sunitinib or placebo. The primary endpoint of PFS at 12 months was achieved by 35.9% of the sunitinib group, meaning that 14 out of 39 patients experienced no progression of their tumor for at least one year. The PFS rate in the placebo group was 18.9%. The median PFS was 8.9 versus 3.6 months in the sunitinib and placebo groups, respectively.

"This is a strong result, showing that the 12-month PFS rate with sunitinib was nearly double that seen with placebo," commented Prof. Juan Valle, Consultant Medical Oncologist, University of Manchester and The Christie NHS Foundation Trust, Manchester, UK. "None of the treatment options we currently have for advanced MPP 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 versus 49% in the placebo group, the most frequent being asthaenia/fatigue (18% versus 3%) and hypertension (10% versus 6%). One death occurred in each arm. Baudin said: "The study demonstrated that sunitinib 37.5 mg per day was tolerable. In particular, we know that two-thirds of patients with MPP have hypertension due to high levels of hormones yet hypertension induced by the drug was manageable."

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."

Nearly one in four (24%) new cancer diagnoses in Europe each year are rare forms of the disease. Around 5.1 million people in the EU live with a rare cancer. In this context, following the European Commission's call for 2021 Thematic Network proposals, Rare Cancers Europe (RCE) submitted an application for "Rare Cancers in All Policies" to address the challenges faced by this community and help achieve the Rare Cancer Agenda 2030.