This was a phase 2 trial assessing the safety and efficacy of axinitib (AXT) in the 1st line for patients with pRCC. The primary endpoint was 24-week progression free survival (PFS), while secondary endpoints included safety, PFS in each histologic subtype of pRCC, OS and best response rate and duration of response.
This was a small study. Inclusion criteria included adult patients (pts) with measurable disease, ECOG PS 0 or 1, no previous treatment, no brain metastases, and adequate organ functions. 56 patients were approached for enrollment, 55 were enrolled. Interestingly, 5 patients were actually excluded after central path review – as they did not have pRCC histology! Ultimately of the 50 eligible patients, 44 were confirmed for inclusion and treated with AXT 5 mg twice daily. Of these 44, 12 had papillary type 1 and 30 had papillary 2. The remaining two patients had either mixed and undetermined papillary histology was enrolled. Basic demographics were: 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.
In terms of outcomes, PFS at 24 weeks is 45.2% for all-comers, but 46.2% and 42.9% in type 1 and 2 pRCC, respectively; best response rate is 26.2% (11/42) with 1 PR and 10 PR in type 1 and 2 respectively. Median PFS is 23.8 weeks for the entire cohort, similar for both subgroups (21.0 for Type 1 and 23.8 for Type 2). Median OS is 18.9 months for the entire cohort, NR for Type 1 and 17.4 for Type 2.
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 27.3%, digestive symptoms 9.1% and PS decrease 5%.
In this first trial of axitinib in mPRC, it shows encouraging efficacy, especially in type 2 pRCC Toxicity was manageable. Axitinib appears as a good candidate to combine with immunotherapy for future trials in mPRC.
Invited Discussant
Dr. Suarez made the following points when addressing this poster presentation.
- This study highlights the importance of pathology review. 5/55 patients (~10%) of patients referred with pRCC were found to not have papillary histology!
- papillary RCC trials group Type 1 and Type 2 together, and separate them out as an afterthought. However, these are two distinct disease processes, with different mutational profiles, different driver mutations (cMET in pRCC Type 1 and fumarate hydratase in pRCC Type 2), and different clinical presentations.
- Prior studies looking at therapies for pRCC have had similar outcomes
- MET inhibitors have had more promise, particularly in MET (+) tumors, with ORR’s approaching 50%
- There are numerous ongoing clinical trials with ICI’s in this disease space
1) Treat on a clinical trial if possible
2) If no clinical trial available, then base the decision on MET status
- MET positive – MET-inhibitor should be used
- MET negative – sunitinib or AXT
However, she again emphasized that we need to stop putting Type 1 and Type 2 pRCC patients in one category for clinical trials!
Presented by: S. Negrier, The University of Lyon, Lyon, France
Invited Discussant: Dr. Cristina Suarez, Spain
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, twitter: @tchandra_uromd, @TjuUrology at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23, 2018, Munich Germany