Citations

4502 Background: Patients with no evidence of disease (NED) after metastasectomy for metastatic renal cell carcinoma (mRCC) are at high risk of recurrence, but no systemic therapy has been shown to benefit this population. Pazopanib is an inhibitor of VEGFR and other kinases that improves progression-free survival in patients with measurable RCC metastatic disease. We performed a randomized, double-blind, placebo-controlled multicenter study to test the hypothesis that pazopanib would improve disease-free survival in patients with mRCC rendered NED after metastasectomy Methods: Patients with NED following metastasectomy were randomized 1:1 to receive pazopanib starting at 800 mg daily vs. placebo for 52 weeks. Patients were stratified by 1 vs. > 1 site of resected disease, and by disease-free interval ≤ vs. > 1 year. Clinical assessment for toxicity and patient-reported outcomes were performed every 4 weeks, and restaging scans every 12 weeks. The study was designed to observe a 42% improvement in disease-free survival (DFS) from 25% to 45% at 3 years. Results: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events had been observed (92% information). The median follow-up from randomization was 30 months (range 0.4 – 66.5 months). The study did not meet the primary endpoint: hazard ratio (95% CI) for DFS was 0.85 (0.55, 1.31) p= 0.47 in favor of pazopanib. At the time of unblinding, 22/129 (17%) of subjects had died. The HR for overall survival (OS) was 2.65 (1.02, 6.9) in favor of placebo ( p= 0.05). Patient-reported outcomes and laboratory correlates will be reported separately. Conclusions: 52 weeks of pazopanib did not improve DFS compared to blinded placebo in patients with mRCC who were NED after metastasectomy. There was a trend toward worse overall survival with pazopanib. Clinical trial information: NCT01575548.

TPS684 Background: The anti-PD-1 antibody nivo improves overall survival in metastatic RCC and is well tolerated. There is no standard adjuvant systemic therapy that increases overall survival (OS) over surgery alone for non-metastatic RCC. Priming the immune system prior to surgery with anti-PD-1 has shown an OS benefit compared to a pure adjuvant approach in mouse solid tumor models. The PROSPER RCC trial aims to improve clinical outcomes by priming the immune system prior to nephrectomy with neoadjuvant nivo and continued engagement with adjuvant blockade in patients with high risk M0 RCC compared to surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is currently accruing patients with clinical stage ≥T2 or node positive M0 RCC of any histology. Tumor biopsy prior to randomization is mandatory to ensure RCC and permits in depth correlative science. The investigational arm will receive two doses of nivo 240mg prior to surgery followed by adjuvant nivo for 9 months (q2 wks x 3 mo followed by 480mg q4 wks x 6 mo). The control arm will undergo standard nephrectomy followed by observation. Randomized patients are stratified by clinical T stage, node positivity, and histology. To enhance accrual and patient quality of life, key upcoming amendments are being instituted. These include biopsy only in the nivo arm, allowance of oligometastatic disease and bilateral renal masses that can be fully resected/ablated, and change of nivo dosing to q4 wks (1 neoadj; 9 adj). With accrual of 766 patients, there is 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival (RFS) at 5 years assuming the ASSURE historical control of ~56% to 70% (HR = 0.70). The study is also powered to evaluate a significant increase in overall survival (HR 0.67). Safety, feasibility, and quality of life endpoints critical to adjuvant therapy considerations are incorporated. PROSPER RCC embeds a wealth of translational work aimed at investigating the impact of the baseline immune milieu, the changes induced by neoadjuvant anti-PD-1 priming, and how both correlate with clinical outcomes. Clinical trial information: NCT03055013.

PURPOSE The objective of this study was to determine the negative predictive value (NPV) of positron emission tomography (PET)/computed tomography (CT) for the clinically N0 neck on the basis of neck dissection. METHODS Participants with newly diagnosed, first-time, head and neck squamous cell carcinoma (HNSCC) and at least one clinically N0 neck side for which dissection was planned were included. A total of 287 participants were prospectively enrolled from 23 American College of Radiology Imaging Network-qualified institutions. PET/CT was compared with findings at neck dissection. RESULTS PET/CT scans and pathology findings were available for 270 N0 neck sides from 212 participants. For visual assessment, the NPV specific to the clinical-N0 sides was 0.868 (95% CI, 0.803 to 0.925). For dichotomized maximum standardized uptake value, the NPVs specific to the nodal basins were 0.940 (95% CI, 0.928 to 0.952) and 0.937 (95% CI, 0.925 to 0.949) at prespecified cutoffs of 2.5 and 3.5, respectively. The optimal cutoff maximum standardized uptake value was determined to be 1.8, with an NPV of 0.942 (95% CI, 0.930 to 0.953). The PET/CT-informed surgical treatment plan was changed in 51 of 237 participants (22%) compared with the PET/CT-blinded surgical plan. In 34 participants (14%), this led to planned dissection of additional nodal levels. In 12 participants (5%), this led to fewer planned dissected nodal levels. Negative PET/CT scans in N0 necks was true negative in 87% and false negative in 13%. CONCLUSION [18F]fluorodeoxyglucose-PET/CT has high NPV for the N0 neck in T2 to T4 HNSCC. The surgical treatment plans on the basis of PET/CT findings may be changed in approximately 22% of this group. These findings suggest that [18F]fluorodeoxyglucose-PET/CT may assist the clinician in deciding on the best therapy for the clinically N0 neck in HNSCC. Well-designed clinical trials should be performed to test the outcome of omitting neck dissection by using PET/CT.