Assessing the effectiveness and safety of lenvatinib and everolimus in advanced renal cell carcinoma: insights from the RELIEVE study's analysis of heavily pretreated patients

Sebastiano Buti; Alessandro Olivari; Cristina Masini; Davide Bimbatti; Donata Sartori; Paola Ermacora; Carlo Cattrini; Maria Giuseppa Vitale; Ernesto Rossi; Claudia Mucciarini; Mimma Rizzo; Michele Sisani; Matteo Santoni; Giandomenico Roviello; Veronica Mollica; Vincenza Conteduca; Francesco Grillone; Marika Cinausero; Giuseppe Prati; Francesco Atzori; Marco Stellato; Francesco Massari; Melissa Bersanelli

doi:10.1177/17562872241244574

Assessing the effectiveness and safety of lenvatinib and everolimus in advanced renal cell carcinoma: insights from the RELIEVE study's analysis of heavily pretreated patients

Ther Adv Urol. 2024 Apr 17:16:17562872241244574. doi: 10.1177/17562872241244574. eCollection 2024 Jan-Dec.

Authors

Sebastiano Buti¹, Alessandro Olivari², Cristina Masini³, Davide Bimbatti⁴, Donata Sartori⁵, Paola Ermacora⁶, Carlo Cattrini⁷, Maria Giuseppa Vitale⁸, Ernesto Rossi⁹, Claudia Mucciarini¹⁰, Mimma Rizzo¹¹, Michele Sisani¹², Matteo Santoni¹³, Giandomenico Roviello¹⁴, Veronica Mollica¹⁵, Vincenza Conteduca¹⁶, Francesco Grillone¹⁷, Marika Cinausero¹⁸, Giuseppe Prati¹⁹, Francesco Atzori²⁰, Marco Stellato²¹, Francesco Massari²², Melissa Bersanelli²³

Affiliations

¹ Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy Oncology Unit, University Hospital of Parma, Parma, Italy.
² Department of Medicine and Surgery, University Hospital of Parma, 14 Gramsci Street, Parma, 43125, Italy Oncology Unit, University Hospital of Parma, Parma, Italy.
³ Oncology Unit, Clinical Cancer Centre AUSL-IRCCS di Reggio, Emilia, Italy.
⁴ Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
⁵ Oncologia Dolo-Mirano, AULSS3 Veneziana, Venezia, Italy.
⁶ Department of Oncology, ASUFC Santa Maria Della Misericordia, Udine, Italy.
⁷ Azienda Ospedaliero-Universitaria 'Maggiore della Carità' - Università del Piemonte Orientale, Novara, Italy.
⁸ Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.
⁹ Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
¹⁰ Medical Oncology Unit, AUSL Modena, Ramazzini Hospital, Carpi, Italy.
¹¹ Azienda Ospedaliera Universitaria Consorziale, Policlinico di Bari, Bari, Italy.
¹² U.O.C. Oncologia Medica, USL Toscana sudest, Arezzo, Italy.
¹³ UOC Oncologia, Ospedale Generale Provinciale di Macerata, Macerata, Italy.
¹⁴ Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze, Italy.
¹⁵ Medical Oncology, IRCCS - Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹⁶ Department of Medical and Surgical Sciences, Unit of Medical Oncology and Biomolecular Therapy, University of Foggia, Policlinico Riuniti, Foggia, Italy.
¹⁷ Medical Oncology Unit, Azienda Ospedaliera Universitaria "Mater-Domini" Policlinico di Catanzaro, Catanzaro, Italy.
¹⁸ Department of Medicine (DAME), University of Udine, Udine, Italy.
¹⁹ Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy.
²⁰ Unità di Oncologia Medica, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, Italy.
²¹ Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
²² Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
²³ University Hospital of Parma, Parma, Italy.

Abstract

Background: The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging.

Objectives: The primary objective was to assess the effectiveness of the lenvatinib plus everolimus combination and the secondary objective was the toxicity profile of this combination.

Design: We conducted a longitudinal retrospective study examining mRCC patients pre-treated with one or more lines of therapy among different cancer centers in Italy.

Methods: The study included patients who received the combination of lenvatinib plus everolimus as either a second-line treatment or beyond. We assessed progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), response rate (RR), and toxicity profile. In addition, we explored the potential relationship between treatment effectiveness and clinical and laboratory parameters.

Results: In all, 33 patients were assessed, the median age was 60 years, 57% had an Eastern Cooperative Oncology Group performance status of 1-2 and. 63% received ⩾ 3 prior lines of therapy. 62% were 'intermediate risk' according to the International Metastatic Renal Cell Carcinoma Database Consortium and 30% were 'poor risk'. The RR was 42% (no complete response), 18% stable disease. Median OS was 11.2 months (95% CI 6.8-19.9), median PFS was 6.7 months (95% CI 0.6-30.8), and median TTF was 6.7 months (95% CI 4.8-16.6). A shorter OS was significantly associated with lymph node metastases (p = 0.043, 95% CI), neutrophils/ lymphocytes ratio (NLR) ⩾ 3 (p = 0.007), hemoglobin/red cell distribution width ratio cutoff value <0.7 was significant (p = 0.03) while a shorter PFS was associated with lung (p = 0.048) and brain metastases (p = 0.023). The most frequent G1 toxicity was diarrhea (24%), G2 was fatigue (30%), and hypertension and skin toxicity (6%) for G3.

Conclusion: Our findings suggest a clinically relevant effectiveness of lenvatinib plus everolimus combination with an acceptable toxicity profile for heavily pretreated patients with mRCC.

Keywords: everolimus; heavily; lenvatinib; mRCC; pretreated; renal cell carcinoma.