Gemcitabine plus platinum-based chemotherapy in combination with bevacizumab for kidney metastatic collecting duct and medullary carcinomas: Results of a prospective phase II trial (BEVABEL-GETUG/AFU24)

Constance Thibault; Aude Fléchon; Laurence Albiges; Charlotte Joly; Philippe Barthelemy; Marine Gross-Goupil; Christine Chevreau; Elodie Coquan; Frédéric Rolland; Brigitte Laguerre; Gwenaelle Gravis; Nicolas Pécuchet; Réza-Thierry Elaidi; Marc-Olivier Timsit; Meryem Brihoum; Edouard Auclin; Aurélien de Reyniès; Yves Allory; Stéphane Oudard

doi:10.1016/j.ejca.2023.03.018

Gemcitabine plus platinum-based chemotherapy in combination with bevacizumab for kidney metastatic collecting duct and medullary carcinomas: Results of a prospective phase II trial (BEVABEL-GETUG/AFU24)

Eur J Cancer. 2023 Jun:186:83-90. doi: 10.1016/j.ejca.2023.03.018. Epub 2023 Mar 23.

Authors

Constance Thibault¹, Aude Fléchon², Laurence Albiges³, Charlotte Joly⁴, Philippe Barthelemy⁵, Marine Gross-Goupil⁶, Christine Chevreau⁷, Elodie Coquan⁸, Frédéric Rolland⁹, Brigitte Laguerre¹⁰, Gwenaelle Gravis¹¹, Nicolas Pécuchet¹², Réza-Thierry Elaidi¹³, Marc-Olivier Timsit¹⁴, Meryem Brihoum¹⁵, Edouard Auclin¹⁶, Aurélien de Reyniès¹⁷, Yves Allory¹⁸, Stéphane Oudard¹⁹

Affiliations

¹ Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP-Centre, Université Paris Cité, Paris, France; Université Paris Cité, AP-HP, Centre de Recherche des Cordeliers INSERM UMR-S 1138, Paris, France.
² Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
³ Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
⁴ Department of Medical Oncology, Hôpital Henri Mondor, Créteil, France.
⁵ Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
⁶ Department of Medical Oncology, Centre hospitalo-Universitaire, Bordeaux, France.
⁷ Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France.
⁸ Department of Medical Oncology, Centre François Baclesse, Caen, France.
⁹ Department of Medical Oncology, Centre René Gauducheau, Saint-Herblin, France.
¹⁰ Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
¹¹ Department of Medical Oncology, Institut Paoli Calmette, Marseille, France.
¹² Department of Medical Oncology, Hôpital d'Instruction des Armées Bégin, Saint Mandé F-94160, France.
¹³ ARTIC: Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, Paris, France.
¹⁴ Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP-Centre, Université Paris Cité, Paris, France; Department of Urology, Hôpital Européen Georges Pompidou, APHP-Centre, France.
¹⁵ UNICANCER, Paris, France.
¹⁶ Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP-Centre, Université Paris Cité, Paris, France.
¹⁷ Université Paris Cité, AP-HP, laboratoire SeQOIA, Centre de Recherche des Cordeliers INSERM UMR-S 1138, Paris, France.
¹⁸ Department of Anatomopathology, Institut Curie, Université Paris Saclay, Saint-Cloud, France; Institut Curie, CNRS, UMR 144, Paris 75248, France.
¹⁹ Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, APHP-Centre, Université Paris Cité, Paris, France; Université Paris Cité, PARCC, INSERM U970, Paris, France. Electronic address: stephane.oudard@aphp.fr.

PMID: 37054556
DOI: 10.1016/j.ejca.2023.03.018

Abstract

Background: Renal medullary carcinoma (RMC) and collecting duct carcinoma (CDC) are rare entities with a poor outcome. First-line metastatic treatment is based on gemcitabine + platinum chemotherapy (GC) regimen but retrospective data suggest enhanced anti-tumour activity with the addition of bevacizumab. Therefore, we performed a prospective assessment of the safety and efficacy of GC + bevacizumab in metastatic RMC/CDC.

Methods: We conducted a phase 2 open-label trial in 18 centres in France in patients with metastatic RMC/CDC and no prior systemic treatment. Patients received bevacizumab plus GC up to 6 cycles followed, for non-progressive disease, by maintenance therapy with bevacizumab until progression or unacceptable toxicity. The co-primary end-points were objective response rates (ORRs) and progression-free survival (PFS) at 6 months (ORR-6; PFS-6). PFS, overall survival (OS) and safety were secondary end-points. At interim analysis, the trial was closed due to toxicity and lack of efficacy.

Results: From 2015 to 2019, 34 of the 41 planned patients have been enroled. After a median follow-up of 25 months, ORR-6 and PFS-6 were 29.4% and 47.1%, respectively. Median OS was 11.1 months (95% confidence interval [CI]: 7.6-24.2). Seven patients (20.6%) discontinued bevacizumab because of toxicities (hypertension, proteinuria, colonic perforation). Grade 3-4 toxicities were reported in 82% patients, the most common being haematologic toxicities and hypertension. Two patients experienced grade 5 toxicity (subdural haematoma related to bevacizumab and encephalopathy of unknown origin).

Conclusion: Our study showed no benefit for bevacizumab added to chemotherapy in metastatic RMC and CDC with higher than expected toxicity. Consequently, GC regimen remains a therapeutic option for RMC/CDC patients.

Trial registration: ClinicalTrials.gov NCT02363751.

Keywords: Adult; Bevacizumab; Chemotherapy; Collecting duct carcinoma; Rare tumours; Renal medullary carcinoma (RMC).

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Bevacizumab
Carcinoma, Medullary* / chemically induced
Carcinoma, Medullary* / drug therapy
Carcinoma, Renal Cell*
Gemcitabine
Humans
Hypertension* / chemically induced
Kidney / pathology
Kidney Neoplasms* / pathology
Platinum / therapeutic use
Prospective Studies
Retrospective Studies

Substances

Bevacizumab
Gemcitabine
Platinum

Associated data

ClinicalTrials.gov/NCT02363751