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Tyrosine Kinase Inhibitor Prolongs Progression-Free Survival in Rare Neuroendocrine Tumours [ESMO Congress 2021 Press Release]

20 Sep 2021
Central Nervous System Malignancies

LUGANO, Switzerland - The first randomised 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. (1)


“This trial provides the highest level of evidence ever reached in this very rare cancer,” said study author Dr. Eric Baudin, Chair, Neuro-Endocrine Tumours, Gustave Roussy - Cancer Campus, Villejuif, France. “The results are practice-changing. Sunitinib is a new option for these patients and becomes the therapy with the most robust indication of antitumour 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.”

MPP is a very rare neuroendocrine tumour, with an annual incidence of less than one per million. During an eight-year period, FIRSTMAPPP enrolled 78 patients with progressive MPP from 15 centres 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 tumour 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 randomised 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 centres. 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. (2)

Notes to Editors

Rare Cancers Europe (RCE) is a multi-stakeholder initiative founded by ESMO and dedicated to putting rare cancers firmly on the European policy agenda.

Call for 2021 Thematic Networks: Of 22 proposals, just five – including RCE’s – were shortlisted and an announcement of the three winners is expected imminently. Successful candidates will develop Joint Statements to advise the European Commission on policy activities.

Please make sure to use the official name of the meeting in your reports: ESMO Congress 2021

Official Congress Hashtag:  #ESMO21


This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.


  1. Abstract 567O_PR ‘First International Randomized STudy in MAlignant Progressive Pheochromocytoma and Paragangliomas (FIRSTMAPPP): an academic double-blind trial investigating sunitinib‘ will be presented by Eric Baudin during Presidential symposium 3 on Monday, 20 September, 15:05 to 16:35 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5
  2. Rare Cancers Europe is a semi-finalist for a Thematic Network.

E. Baudin1, B. Goichot2, A. Berruti3, J. Hadoux4, S. MOALLA5, S. Laboureau6, S. Noelting7, C. de la Fouchardière8, T. Kienitz9, T. Deutschbein10, S. Zovato11, L. Amar12, A. Tabarin13, H.J. Timmers14, P. Niccoli15, A. Faggiano16, F. Beuschlein17, M. Attard18, M. Texier19, M. Fassnacht20 

1Endocrine Oncology, Gustave Roussy - Cancer Campus, Villejuif, France, 2Internal Medicine And Endocrinology, Hopital de Hautepierre - Hopitaux Universitaires de Strasbourg, Strasbourg, France, 3Department Of Medical And Surgical Specialties, Radiological Sciences, And Publi, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy, 4Endocrine Oncology, Institut Gustave Roussy, Villejuif, France, 5Imaging Departement, Institut Gustave Roussy, Villejuif, France, 6Endocrinology, Hopitaux Universitaire d'Angers, Angers, France, 7Medizinische Klinik Und Poliklinik Iv, MediziKlinikum der Universität München, Munchen, Germany, 8Department Of Medical Oncology, Léon Bérard Center, Lyon - EORTC Endocrine Tumours Group, France, 9Department Of Endocrinology And Metabolism, Charité Universitätsmedizin Berlin, Berlin, Germany, 10Department Internal Medicine I, Division Of Endocrinology And Diabetes, University Hospital Würzburg, Würzburg, Germany, 11Hereditary Tumors Unit-oncological Endocrinology, Istituto Oncologico Veneto-IRCCS, Padova, Italy, 12Paris, HEGP - Hopital Europeen Georges-Pompidou - AP-HP, Paris, France, 13Department Of Endocrinology, University of Bordeaux, Bordeaux, France, 14Internal Medicine, Radboud University Medical Center, Nijmegen, Nijmegen, Netherlands, 15Oncology, Institut Paoli Calmette, Marseille, France, 16Department Of Clinical And Molecular Medicine, Sapienza University of Rome, Rome, Italy, 17Endocrine Research, LMU Klinikum der Universität München, Munich, Germany, 18Ile De France, Gustave Roussy - Cancer Campus, Villejuif, France, 19Head And Neck Cancer, Institut Gustave Roussy, Villejuif, France, 20Department Of Internal Medicine I - Division Of Endocrinology, University Hospital Würzburg, Würzburg, Germany 

Background: Malignant pheochromocytoma and paraganglioma (MPP) is a very rare cancer (annual incidence < 1 per million). Here, we report the first academic randomized double-blind phase II study results assessing Sunitinib efficacy compared to placebo (FIRSTMAPPP trial: NCT01371201).

Methods: Patients with progressive MPP with 1.5year according to (RECIST) were randomized 1/1 for Sunitinib therapy 37.5 mg/d or Placebo and stratified for SDHB status and line of treatment. Primary endpoint: progression-free survival (PFS) at 12 months according to real-time central review (RECIST 1.1), analyzed every 3 months (ITT). Key secondary endpoints: ORR, response (delay, duration), overall PFS, overall survival, safety (NCI CTCAE v.4). On the basis of a two-step Simon model (alpha 10%, power 90%), we aimed for 74 patients, assuming a PFS improvement at 12 months from 20 to 40%. 11 or more patients out of 37 with no progression at 12 months were expected to conclude that Sunitinib is effective. The placebo group served as an internal control to validate the hypothesis of the Simon design with a 12-m PFS equal to 20%. An IDMC was set up to review the accrual, toxicity, and interim analysis.

Results: 78 patients were enrolled (median age, 53 yrs; 59% men). Main characteristics: adrenal/PGL primaries, each 50%; 32% SDHx inherited, 71% secreting, distant lymph node/bone/lung/liver mets, 73%/65%/51%/49%; 60% prior therapy. 39 patients were randomized in each arm. The primary endpoint was met: PFS at 12 months was 35.9% (Sunitinib) vs. 18.9% (Placebo; within the 90%CI confirming the Simon design conclusion). Median PFS was 8.9 (95CI: 5.5-12.7) vs. 3.6 months (3.1-6.1). Reasons for drug discontinuation were AE/tumor progression in 14%/64% (Sunitinib) and 0%/86% (Placebo). 54% patients with Sunitinib vs. 49% with Placebo experienced SAE; most frequent grade 3-4 were asthenia/fatigue (18% vs. 3%) and hypertension (10% vs. 6%).One death occurred in each arm.

Conclusions: After 8 years of enrolment, this first randomized study in the field of MPP provides the highest level of evidence ever reached in this very rare cancer. Sunitinib becomes the first-line option in patients with progressive MPP.

Clinical trial identification: NCT01371201

Legal entity responsible for the study: Gustave Roussy 

Funding: Foundation or academic group WITH funding from a pharma, biotech, or other commercial company-  Pfizer (provided sunitinib and placebo for the study) 

Disclosure: E. Baudin: Financial Interests, Personal and Institutional, Advisory Board, research grant and principal investigator: Novartis; Financial Interests, Personal and Institutional, Advisory Board, and research grant: HRA; Financial Interests, Personal and Institutional, Project Lead, Principal investigation: Ipsen; Financial Interests, Personal and Institutional, Advisory Board, research grant (drug supply for trial): AAA; Financial Interests, Personal and Institutional, Research Grant, drug supply for trial: Pfizer; Financial Interests, Personal and Institutional, Advisory Board: Hutchinson Pharma. 
All other authors have declared no conflicts of interest. 

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