1884MO - Phase II study of avelumab (Ave) plus intermittent axitinib (Axi) in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC): The TIDE-A study

Background

Combinations (combos) of VEGFR-TKI plus anti-PD1/L1 immunotherapy (IO) are the standard of care for first-line therapy of mRCC pts due to increased response rate, prolonged progression-free (PFS) and overall (OS) survivals compared to TKI alone. It is well recognized that the majority of toxicities of the combos are due to the TKI.

Methods

mRCC pts with prior nephrectomy, and with no symptomatic/bulky disease nor liver mets, were treated with Ave 800 mg flat dose IV Q2W + Axi 5 mg PO BID for 36 weeks (W). At W36, pts who achieved RECIST partial response (PR) discontinued Axi and continued Ave until disease progression (PD) or unacceptable toxicity. In case of PD, they re-started Axi for 24W and discontinued it again in case of new PR while continuing Ave. Pts with stable disease at 36W continued the combo until PD or unacceptable toxicity. Primary endpoint: rate of pts free of progression (FoP) after 8W from Axi discontinuation (≥48%). Secondary endpoints: median PFS, objective response rate (ORR) and safety. 75 pts have been planned to be enrolled.

Results

79 pts were enrolled and 75 evaluated for efficacy (IMDC risk: 40.0% favorable, 57.3% intermediate, 2.7% poor). A total of 29 (38.2%) pts discontinued Axi at 36W; the rate of pts FoP after 8W was 72.4%. With a median follow-up of 19.3 mos, the mPFS was 23.8 mos (95%CI, NR-NR) with 70% of pts FoP at 18 mos; mOS was not reached. The ORR was 76.0% (12.0% CR, 64.0% PR); 18.7% had SD and 4.0% had PD. The median duration of first Axi discontinuation was 16.0 weeks (95%CI, 10.9 – 21.1). Among the 29 pts who discontinued Axi, 9 were still ongoing, 20 had PD and 19 restarted Axi (9 ongoing, 6 had further PD, 4 discontinued Axi again). Safety: 96.2% of pts had at least one adverse event (AE) and 40.5% had G3-G4 AEs with no treatment-related death. All-grades and G3-G4 axitinib-related AEs were reported in 34.2% and 11.4% of overall pts, respectively, and in 10.3% and 0% of those who discontinued Axi.

Conclusions

The TIDE-A study shows that TKI discontinuation is safe for selected mRCC pts with evidence of response to TKI+IO combos in first line. Axi discontinuation allows decreasing of toxicity, while maintaining the possibility of Axi benefit in case of its reintroduction.

Clinical trial identification

NCT04698213.

Editorial acknowledgement

Legal entity responsible for the study

Consorzio Oncotech (info@oncotech.org).

Funding

This work was financially supported by Pfizer, as part of an alliance between Pfizer and Merck (CrossRef Funder ID: 10.13039/100009945).

Disclosure

R. Iacovelli: Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Merck, Ipsen, Astellas; Financial Interests, Personal, Advisory Board: MSD, Janssen, BMS, Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Speaker’s Bureau: AAA. C. Ciccarese: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, Ipsen; Financial Interests, Personal, Other, travel grant: Pfizer. M. Bersanelli: Financial Interests, Institutional, Research Funding: Roche, Pfizer, Novartis, BMS, AstraZeneca, Sanofi; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Ipsen, AstraZeneca, Pierre Fabre, Pfizer; Financial Interests, Personal, Advisory Board: Ipsen, Novartis, Sanofi, Pierre Fabre, Merck; Financial Interests, Personal, Other, copyright transfer: Pfizer, MSD, Ipsen, Sanofi, Sciclone Pharmaceuticals. P.A. Zucali: Financial Interests, Personal, Other, advisory role, speaker engagements and travel and accommodation expenses: MSD, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, BMS, Amgen, Roche, Bayer. C. Masini: Financial Interests, Personal, Invited Speaker: Ipsen, Astellas, BMS; Financial Interests, Personal, Leadership Role: MSD; Financial Interests, Personal, Advisory Role: BMS, Astellas, Ipsen, MSD, AstraZeneca, Janssen, Merck Serono. F. Massari: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, Janssen, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: BMS, Ipsen. S. Buti: Financial Interests, Personal, Advisory Board: BMS, Pfizer, MSD, MSD, Ipsen, AstraZeneca, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: BMS, MSD, Ipsen, AstraZeneca, Novartis; Financial Interests, Institutional, Local PI: BMS, Ipsen, AstraZeneca; Financial Interests, Institutional, Coordinating PI: BMS, MSD; Financial Interests, Institutional, Research Grant: Novartis; Non-Financial Interests, Other, Member of panel for kidney cancer guidelines: AIOM (Italian Association of Medical Oncology); Non-Financial Interests, Other, member and coordinator of the “Rare Tumors” group: Meet-URO group (Italian Network For Research In Urologic-Oncology). All other authors have declared no conflicts of interest.