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).

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.

Informations de copyright

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Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Constance Thibault has received honoraria from AAA, Astellas, Astra Zeneca, Bristol-Myers Squibb, Janssen, Ipsen, Merck, Pfizer and Sanofi. Aude Fléchon: None. Laurence Albiges: Advisory or Consulting or Honoraria, (all paid to Institution) Astellas – BMS – Ipsen – Janssen – MSD – Pfizer – EISAI – Roche. Charlotte Joly: has received honoraria from Astellas and Ipsen. Philippe Barthelemy: has received honoraria from BMS, Pfizer, Merck, MSD, Novartis, IPSEN, Janssen Cilag, AMGEN, Bayer, Gilead, Astra Zeneca, Astellas, Bayer, Esai, Amgen. Marine Gross-Goupil: Consulting or Advisory Role –Astellas, BMS, Esai, Janssen, Ipsen, MSD, Pfizer, Roche. Travel, Accommodations, Expenses – MSD, Bayer, Pfizer. Christine Chevreau: None. Elodie Coquan: Ipsen, Pfizer (paid to institution), Ipsen, MSD, Astra Zeneca, BMS (paid to EQ). Frédéric Rolland: None. Brigitte Laguerre: None. Gweanelle Gravis: Speaker bureau: Janssen, Amgen, BMS, IPSEN, AAA, Astra Zeneca, Bayer, Pfizer Merck, Astellas. Recipient institution. Board: Janssen, Amgen, BMS, Curium, Bayer, Pfizer Merck. Recipient my institution. Expert: BMS, Bayer, Pfizer/ merck. Recipient my institution. Travel expense: Janssen, BMS, Astra Zeneca, Bayer, Pfizer, Merck. Recipient: GG. Nicolas Pécuchet: is an employee at Dassault Systèmes. Réza-Thierry Elaidi: None. Marc-Olivier Timsit: has received honoraria from Janssen, MSD, Astellas, Ipsen, Olympus. Meryem Brihoum: None. Edouard Auclin: has received honoraria from Amgen Sanofi Genzyme. Aurélien de Reynies: None. Yves Allory: None. Stéphane Oudard has received honoraria from Astellas, Bayer, Bristol-Myers Squibb, Janssen, Merck, Novartis, Pfizer, and Sanofi.