Combinations of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitor (ICI) against PD1/PD-L1 are the standard first-line therapy for patients with metastatic renal cell carcinoma (mRCC), irrespective of the prognostic class.
To investigate the feasibility and safety of withdrawing VEGFR-TKI but continuing anti-PD1/PD-L1 in patients who achieve a response to their combination.
This was a single-arm phase 2 trial in patients with treatment-naïve mRCC with prior nephrectomy, without symptomatic/bulky disease and no liver metastases.
Enrolled patients received axitinib + avelumab; after 36 wk of therapy those who achieved a tumour response interrupted axitinib and continued avelumab maintenance until disease progression.
The primary endpoint was the rate of patients without progression 8 wk after the axitinib interruption. The secondary endpoints were the median value for progression-free (mPFS) and overall (mOS) survival and the safety in the overall population.
Seventy-nine patients were enrolled and 75 were evaluated for efficacy. A total of 29 (38%) patients had axitinib withdrawn, as per the study design, with 72% of them having no progression after 8 wk and thus achieving the primary endpoint. The mPFS of the overall population was 24 mo, while the mOS was not reached. The objective response rate was 76% (12% complete response and 64% partial response), with 19% of patients having stable disease. In the patients who discontinued axitinib, the incidence of adverse events of any grade was 59% for grade 3 and 3% for grade 4. This study was limited by the lack of a comparative arm.
The TIDE-A study demonstrates that the withdrawal of VEGFR-TKI with ICI maintenance is feasible for selected mRCC patients with evidence of a response to the VEGFR-TKI + ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance leads to decreased side effects and should be investigated further as a new strategy to delay tumour progression.
We evaluated whether certain patients with advanced kidney cancer treated with the fist-line combination of axitinib plus avelumab can interrupt the axitinib in case of a tumour response after 36 wk of therapy. We found that axitinib interruption improved the safety of the combination, while the maintenance with avelumab might delay tumour progression.
European urology. 2024 Mar 22 [Epub ahead of print]
Roberto Iacovelli, Chiara Ciccarese, Sebastiano Buti, Paolo Andrea Zucali, Emanuela Fantinel, Davide Bimbatti, Elena Verzoni, Caterina Accettura, Lucia Bonomi, Consuelo Buttigliero, Giuseppe Fornarini, Stefania Pipitone, Francesco Atzori, Cristina Masini, Francesco Massari, Francesca Primi, Alessandro Strusi, Giulia Claire Giudice, Matteo Perrino, Marco Maruzzo, Michele Milella, Diana Giannarelli, Matteo Brunelli, Giuseppe Procopio, Giampaolo Tortora
Oncology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy; Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: ., Oncology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy., Department of Medicine and Surgery, University of Parma, Parma, Italy., Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Medical Oncology, Humanitas Research Hospital Humanitas Cancer Center, Rozzano, Italy., Medical Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Oncology Unit 1, Istituto Oncologico Veneto, IOV - IRCCS, Padua, Italy., SSD Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Medical Oncology, Vito Fazzi Hospital, Lecce, Italy., Department of Oncology and Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy., Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy., UO Oncologia Medica 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy., Medical Oncology, University Hospital and University of Cagliari, Cagliari, Italy., Medical Oncology, Comprehensive Cancer Centre IRCCS - AUSL Reggio Emilia, Reggio Emilia, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Medical Oncology, Central Hospital of Belcolle, Viterbo, Italy., Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, Rome, Italy., Medical Oncology, Humanitas Research Hospital Humanitas Cancer Center, Rozzano, Italy., Medical Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Department of Medicine, University of Verona, Verona, Italy., Biostatistics Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy., Department of Diagnostics and Public Health, Pathology Unit, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy., Oncology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy; Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.