SAVOIR trial: Savolitinib versus Sunitinib in patients with MET-driven papillary renal cell carcinoma


Papillary renal cell carcinoma ( PRCC ) is the most common type of non-clear cell RCC, accounting for 10–15% of renal malignancies.
As a subset of PRCC cases are MET-driven, MET inhibition may be an appropriate targeted treatment approach.

In a single-arm phase II study, Savolitinib, a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in patients with MET-driven PRCC ( Choueiri et al. JCO 2017 ).
The phase III SAVOIR study further assessed Savolitinib versus standard of care Sunitinib in patients with MET-driven papillary renal cell carcinoma.

In this open-label ( sponsor blinded ), randomized study, patients with centrally confirmed MET-driven ( MET and/or HGF amplification, chromosome 7 gain and/or MET kinase domain mutations ), metastatic papillary renal cell carcinoma were randomized to Savolitinib 600 mg once daily ( QD ), or Sunitinib 50 mg QD 4 weeks on / 2 weeks off.

Primary objective was progression-free survival ( PFS; RECIST 1.1 by blinded independent central review ).
Secondary objectives included overall survival ( OS ), objective response rate ( ORR ), and safety and tolerability.

After external data on predicted progression-free survival with Sunitinib in patients with MET-driven disease became available, study enrollment was closed.
At data cutoff ( Aug 2019 ), only 60 of the planned 180 patients were randomized ( Savolitinib n = 33; Sunitinib n = 27 ).
Most had chromosome 7 gain ( Savolitinib 91%; Sunitinib 96% ) and no prior therapy ( Savolitinib 85%; Sunitinib 93% ).

Progression-free survival, overall survival, and objective response rate were numerically improved with Savolitinib versus Sunitinib: PFS 7.0 vs 5.6 months; OS NR ( not reached ) vs 13 months; ORR ( all partial responses ) 27% vs 7%.

CTCAE grade greater than or equal to 3 adverse events were reported in 42% and 81% of patients; dose modifications were related to adverse effects in 30% and 74% of patients with Savolitinib and Sunitinib respectively.

After discontinuation, 36% of all Savolitinib and 19% of all Sunitinib patients received subsequent anticancer therapy.

In conclusion, although patient numbers and follow-up were limited, Savolitinib demonstrated encouraging efficacy and an improved safety profile versus Sunitinib, with fewer grade 3 or more adverse effects and fewer dose modifications required.
Sunitinib performance was poorer than expected based on external retrospective. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020

XagenaMedicine_2020



Indietro

Altri articoli

Data from the five-year analysis featuring extended follow-up from the phase III COMBI-AD study have confirmed that 12 months of...


There has been an only indirect comparison between Pembrolizumab ( Keytruda ) and Pembrolizumab plus chemotherapy in patients with non-small...


The aim of neo-adjuvant therapy in locally advanced or oligometastatic melanoma is to facilitate radical resection, improve outcomes and undertake...


The ALEX study has demonstrated significantly improved progression-free survival ( PFS ) with Alectinib ( Alecensa ) versus Crizotinib (...


In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for...


The mRNA-1273 vaccine for SARS-CoV-2 is tolerable and immunogenic in older adults. Data on prolonged immunogenicity and effectiveness in preventing severe...


The European Commission ( EC ) has granted conditional marketing authorization to Ayvakyt ( Avapritinib ) as a monotherapy for...


The U.S. Food and Drug Administration ( FDA ) has approved Gallium 68 PSMA-11 ( Ga 68 PSMA-11 ), the...


The FDA ( U.S. Food and Drug Administration ) has approved Ayvakit ( Avapritinib ) for the treatment of adults...


The European Commission ( EC ) has granted marketing authorisation for the expanded use of Erleada ( Apalutamide ) to...