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

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  1 , Alessandro Olivari  2 , Cristina Masini  3 , Davide Bimbatti  4 , Donata Sartori  5 , Paola Ermacora  6 , Carlo Cattrini  7 , Maria Giuseppa Vitale  8 , Ernesto Rossi  9 , Claudia Mucciarini  10 , Mimma Rizzo  11 , Michele Sisani  12 , Matteo Santoni  13 , Giandomenico Roviello  14 , Veronica Mollica  15 , Vincenza Conteduca  16 , Francesco Grillone  17 , Marika Cinausero  18 , Giuseppe Prati  19 , Francesco Atzori  20 , Marco Stellato  21 , Francesco Massari  22 , Melissa Bersanelli  23
Affiliations

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 et al. Ther Adv Urol. .

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.

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Conflict of interest statement

V.C. has served as a consultant/advisory board member for Janssen, Astellas, Merck, AstraZeneca, Amgen, and Bayer and has received speaker honoraria or travel support from Astellas, Janssen, Ipsen, Bayer, and Sanofi. E.R. had a role as consultant for Bristol Meyers Squibb, MSD, Novartis, Pierre Fabre, Immunocore, and Pfizer.

Figures

Figure 1.
Figure 1.
Overall survival curve.
Figure 2.
Figure 2.
Progression-free survival curve.
Figure 3.
Figure 3.
Time to treatment failure curve.
Figure 4.
Figure 4.
(a) Correlation between OS and node metastases at diagnosis. (b) Correlation between NLR values and OS. (c) Correlation between Hb/RDW and OS. Hb/RDW, red cell distribution width; NLR, neutrophils/ lymphocytes ratio; OS, overall survival.
Figure 5.
Figure 5.
(a) Correlation between lung metastases and PFS. (b) Correlation between brain metastases and PFS. PFS, progression-free survival.
See this image and copyright information in PMC

References

    1. Associazione Italiana di Oncologia Medica, 2022 – “I numeri del cancro in Italia” , https://www.registri-tumori.it (accessed 6 October 2023).
    1. Tannir NM, Pal SK, Atkins MB. Second-line treatment landscape for renal cell carcinoma: a comprehensive review. Oncologist 2018; 23: 540–555. - PMC - PubMed
    1. Shah AY, Kotecha RR, Lemke EA, et al.. Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors. Eur J Cancer 2019; 114: 67–75. - PMC - PubMed
    1. Campbell MT, Bilen MA, Shah AY, et al.. Cabozantinib for the treatment of patients with metastatic non-clear cell renal cell carcinoma: a retrospective analysis. Eur J Cancer 2018; 104: 188–194. - PubMed
    1. Deuker M, Chun FKH, Karakiewicz PI. Second-line tyrosine kinase inhibitor-therapy after immunotherapy-failure. Curr Opin Support Palliat Care 2020; 14: 276–285. - PubMed

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