Iacovelli, Roberto, Ciccarese, Chiara, Buti, Sebastiano, Zucali, Paolo Andrea, Fantinel, Emanuela, Bimbatti, Davide, Verzoni, Elena, Accettura, Caterina, Bonomi, Lucia, Buttigliero, Consuelo, Fornarini, Giuseppe, Pipitone, Stefania, Atzori, Francesco, Masini, Cristina, Massari, Francesco, Primi, Francesca, Strusi, Alessandro, Giudice, Giulia Claire, Perrino, Matteo, and Maruzzo, Marco
Continuous treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor + immunotherapy against the PD1 is one option for upfront treatment of metastatic renal cell carcinoma, but this is characterised by toxicity leading to treatment interruption or discontinuation. The TIDE-A investigated the axitinib withdrawal and avelumab maintenance in patients achieving a response during the combo treatment, reporting resolution of axitinib-related toxicity. The median progression-free survival was 23.8 mo, while the duration of treatment interruption was 16 wk. Combinations of VEGFR-TKIs plus ICI against PD1/PD-L1 are the standard first-line therapy for patients with mRCC, irrespective of the prognostic class. This study aims to investigate the feasibility and safety of withdrawing the VEGFR-TKI but continuing the anti- PD1/PD-L1 in patients who achieve 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 weeks of therapy those who achieved tumor response interrupted axitinib and continued avelumab maintenance until disease progression. The primary endpoint was the rate of patients without progression eight weeks after the axitinib interruption. Secondary endpoints were the median value for progression free (mPFS) and overall survival (mOS) and the safety in the overall population. 79 patients were enrolled and 75 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 A total of 29 (38%) patients had axitinib withdrawn, as per the study design, with 72% of them having no progression after eight weeks and thus achieving the primary endpoint. The mPFS of the overall population was 24 months while the mOS was not reached. The ORR was 76% (12% CR, 64% PR), with 19% of patients having stable disease. In the patients who discontinued axitinib, the incidence of AEs of any grade was 59% and 3% for grade 3 or 4. This study was limited by the lack of the 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 response to the VEGFR-TKI+ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance led to decreased side effects and should be further investigated as a new strategy to delay tumor progression. [ABSTRACT FROM AUTHOR]