Efficacy and safety of neoadjuvant toripalimab plus axitinib in renal cell carcinoma with tumor thrombus: A combined analysis of two phase II trials.

4535 Background: Tumor thrombectomy for renal cell carcinoma (RCC) with tumor thrombus (TT) is associated with high morbidity and mortality. Two trials have demonstrated the efficacy and safety of neoadjuvant toripalimab plus axitinib in patients with TT. Here, we present the pooled analysis results. Methods: These two phase II trials (NEOTAX and NCT04118855) shared similar target populations. Patients with clear cell RCC (ccRCC) and TT received up to 12 weeks of toripalimab plus axitinib before surgery. The primary endpoint was the downstaging rate of TT based on the Mayo classification. For level 0 thrombus, the downstaging defined as: for right RCC, the proximal end of TT retracted from the main renal vein to branches of the renal vein; for left RCC, the superior mesenteric artery (SMA) was an anatomical landmark, the TT retracted from lateral to the abdominal aorta to the level of SMA or from the main renal vein lateral to SMA or the branches of the renal vein. Secondary endpoints included response rate, change in thrombus length, surgical morbidity, progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 40 patients were enrolled, 4 (10%), 4 (10%), 14 (35%), 7 (17.5%), 11 (27.5%) patients had level 0, I, II, III, IV tumor thrombus, respectively. After 12 weeks treatment, 45.0% (18/40) patients experienced a reduction in TT level, one patient (2.5%) had an increase in Mayo level. Thirty-six (90%) patients exhibited shrinkage in TT length, with a median reduction of 1.9 cm (IQR: 0.9 to 3.7 cm). According to the RECIST criteria, the objective response rate and disease control rate of overall tumor was 37.5% and 97.5%. In total, 35 patients underwent radical nephrectomy with IVC thrombectomy, including 16 open, 2 laparoscopic and 17 robotic. No patient had a surgery delay due to treatment-related adverse events (TRAEs). 54.3%(19/35) patients experienced changes in surgical strategy compared with planned surgery. Median operation time was 300 min (IQR: 180-420 min). Median estimated blood loss was 700 ml (IQR: 300-1800 ml). The postoperative complication rate was 60% (21/35), including three (8.6%) major complications and one (2.9%) postoperative death. The most common TRAEs included hypertension (35.0%), proteinuria (35.0%), fatigue (27.5%), and diarrhea (22.5%). Grade ≥3 adverse events were reported in 27.5% (11/40) of patients, no patients experienced Grade 4 or 5 TRAEs. With a median follow-up of 32.2 (IQR: 27.0-35.5) months, the median PFS and OS were not reached. The estimated PFS rate at 1 year was 87.5% (95% CI, 72.4% to 95.3%). The PFS (P = 0.20) and OS (P = 0.44) were similar between responders (partial response) and non-responders (stable disease or progressive disease). Conclusions: Toripalimab in combination with axitinib downstages TT level in a significant proportion of patients leading to simplification in the procedure of surgery. Clinical trial information: NCT04118855 .