Combination anti-angiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes.

Abstract

630 Background: Emerging phase III data support combination antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) as front line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol experience and later line treatment with this therapeutic approach including tolerance, response and survival. Methods: We conducted a retrospective analysis of mRCC patients (pts) who received combination TKI-IO between 11/2015 and 05/2018 at MD Anderson Cancer Center. Chart review detailed baseline characteristics, TKI-IO treatment, toxicity and survival. An independent radiologist, blinded to pts history and clinical data, assessed radiographic response using RECIST v1.1. Results: 36 mRCC pts were identified for study inclusion: median (med) age 63.5 years, 72% clear cell histology, 53% intermediate risk (19% good, 28% poor) by IMDC, med metastatic sites 2, med prior therapies 2, previous TKI 94% and previous IO 47%. Combinations included nivolumab (nivo)-cabozantinib (15), nivo-low dose pazopanib(ldP) (13), nivo-axitinib (5), nivo-lenvatinib (2) and pembrolizumab-axitinib (1). Median time on TKI-IO was 5.6 months (m) (95% CI: 5.2 - 7.7). 56% of pts initiated TKI prior to IO addition at progression and 36% of pts initiated IO prior to TKI addition. ORR was 35% (29% PR and 6% CR); disease control rate was 78% (43% stable disease). With med follow-up of 8.0 m (95% CI: 6.4 – 9.4), med PFS was 7.7 m (95%CI: 5.8 - 9.5), med OS was not reached. Med PFS for pts receiving nivo-ldP was not reached. TKI-IO therapy was well tolerated with only 1 pt demonstrating grade 3 or 4 immune related toxicity (nephritis). 92% of pts experienced any grade of adverse events (ADE) with ADE of interest as follows: diarrhea (25%), hypothyroidism (17%), and pneumonitis (8%). Conclusions: To our knowledge, this is the first case series of off-label combinations of TKI-IO for mRCC. TKI-IO, particularly nivo-ldP, is safe, well tolerated and efficacious. Although further prospective research is essential, TKI-IO could be considered for select mRCC patients, particularly in the setting of TKI or IO refractory disease.