1701 - Efficacy and safety of axitinib in metastatic papillary renal carcinoma (mPRC): results of a GETUG multicenter phase II trial (Axipap)

Background

PRC represents 10-15% of renal carcinomas; there is no standard treatment at the metastatic stage. Few trials were conducted with sunitinib, everolimus and more recently savolitinib, with disappointing response rates. Axitinib, an inhibitor of VEGF receptors, indicated as 2d line treatment in advanced renal cell carcinoma was investigated.

Methods

Axipap is a French multicentre phase II study. A central pathology review was required before inclusion. Other criteria were adult patients (pts) with measurable disease, ECOG PS 0 or 1, no previous treatment, no brain metastases and adequate organ functions. Axitinib was started at 5 mg twice a day orally with dose adaptations according to the recommendations. Primary endpoint was the progression free rate (PFR) at 24 weeks. A minimum of 42 evaluable pts were required to show that 45% (one sided 95% lower limit) pts did not progress at 24 weeks.

Results

55 pts were screened, papillary was not confirmed in 5 (9.1%), 6 (10.9%) had other exclusion criteria. 44 pts, 12 and 30 papillary type 1 and 2, respectively, 1 mixed and 1 undetermined were enrolled. Median age was 65 (27-82), 84% pts were males, 23.8% were in the good, 45.2% in the intermediate and 31% pts in the poor IMDC prognostic groups. The median follow up time is 13.9 months (0.5-21), 5 pts did not yet reach 24 weeks. PFR at 24 weeks is 47.4% (95%CI 34.0-/), 50% (95%CI 24-/) and 46.4% (95%CI 30.9-/) in type 1 and 2 respectively; best response rate is 26.8% (11/41) with 1 PR and 10 PR in type 1 and 2 respectively, median response duration is 24.4 weeks (15-55). Median PFS is 24.7 weeks (95%CI 21-38). At the time of this analysis, 16 pts (36.4%) have died. Treatment related all grade toxicity was as expected with fatigue 73%, hypertension 61%, dysphonia 55%, diarrhea 52%, loss of appetite 30%, hand-foot syndrome 23%; grade 3-4 events were hypertension 25%, digestive symptoms 9% and PS decrease 5%.

Conclusions

This first trial of axitinib in mPRC shows encouraging efficacy, especially in type 2 PRC. Toxicity was manageable. Axitinib appears as a good candidate to combine with immunotherapy for future trials in mPRC. Expert pathology review should be recommended in this setting.

Clinical trial identification

EudraCT: 2014-005426-36.

Legal entity responsible for the study

Centre Leon Bérard, Lyon, France.

Funding

Pfizer.

Editorial Acknowledgement

Disclosure

S. Negrier: Honoraria: Pfizer, BMS, Ipsen, Eusapharma, Novartis; Research grant: Pfizer; Travels: Pfizer, BMS, Ipsen. N. Rioux-Leclercq: Honoraria: Pfizer, Ipsen. A. Ravaud: Honoraria: Pfizer, Novartis, BMS, Roche, Ipsen; Meeting accommodations: Pfizer, Novartis, BMS, Roche, Ipsen. G. Gravis: Travel funding: Pfizer, BMS. L. Geoffrois: Honoraria: Ipsen, BMS, Novartis; Travels: Ipsen, Jansen, BMS, MSD, Merck. C.M. Chevreau, F. Rolland: Honoraria: Novartis, Pfizer, BMS, Ipsen. D. Perol: Honoraria: AstraZeneca, Roche, Janssen, Ipsen. M. Gross Goupil: Honoraria: Pfizer, Ipsen, Novartis, BMS, Roche. A. Flechon: Honoraria: Pfizer, Novartis, Astellas, Sanofi, Janssen, Roche, BMS, MSD. L. Albiges: Consulting: BMS, Novartis; Grant funding: Amgen, Pfizer, BMS, Ipsen, Novartis, Roche, Astellas. B. Escudier: Honoraria: Pfizer, Novartis, BMS, Roche, Ipsen, EUSA Pharma. All other authors have declared no conflicts of interest.