SUO 2018: Adjuvant Therapies in Kidney Cancer: FDA Panel Insights

Phoenix, Arizona ( Dr. Agrawal presented the findings of a recent FDA panel for adjuvant therapies in renal cell carcinoma. He reviewed workshop goals which included reviewing the eligibility criteria used for adjuvant RCC trials, radiographic eligibility, and definitions of disease recurrence in the absence of biopsy. Eligibility criteria are an important focus of the workshop particularly given significant variability in the number of recruits in individual trials depending on specific inclusion criteria.  Solutions for low accrual have included including patients with non-clear cell RCC (preferably in an independent cohort) and including patients with renal insufficiency in checkpoint trials if renal limitations do not impact the outcomes of the trial. 

With regards to timing and length of adjuvant therapy, they concluded that adjuvant therapy would ideally start between 4-16 weeks postoperatively to allow time for healing. No consensus was reached on the ideal length of treatment, and that mechanism-of-action drugs may necessitate variable durations. With regards to surgical considerations, the panel recommended that patients be stratified by radical versus nephron-sparing approaches. They also recommended that patients with microscopically positive margins be judiciously included with consideration for statistical stratification when possible. There was no general consensus regarding the performance of prophylactic lymph node dissection, but the panel agreed that all suspicious regional and positive lymph nodes should be resected. For locally advanced T3-T4 disease, a templated retroperitoneal lymph node dissection was recommended.

The panel reviewed principles of radiologic imaging. They recommended cross-sectional imaging of the chest, abdomen, and pelvis within 4 weeks prior to entering the trial. CT chest is recommended over CXR due to higher sensitivity. PET does not have a well-defined role and should not be required, but may be complementary to CT or MRI. A biopsy was recommended for radiologically suspicious lesions to determine whether residual disease is present. In cases where it is not safe or possible, indeterminate radiographic lesions should be managed uniformly, with a general preference for enrolling patients into the trial. With respect to radiographic recurrence, several specific criteria were introduced. Recurrence was pronounced for lesions ≥ 1 cm if not previously seen on cross-sectional imaging. For pre-existing lesions <1 cm, then > 50% of growth in the long axis on 2 exams was considered a recurrence. For pre-existing lesions, ≤ 1 cm, > 50 % growth in the long axis on a single exam was considered a recurrence. Additional recurrence criteria included multiple sub-centimeter lesions if present in suspicious locations or radiographically concerning for metastatic disease.

Patient perspectives were an important focus of discussion with special attention to the importance of informed consent and honesty in describing the trial. The possibility of unblinding after the initial treatment before proceeding to the next treatment was recommended despite issues with bias. And finally, avoiding unnecessary interventions and procedures in the study protocol because mandatory interventions (e.g. biopsies) can be very stressful to patients. Transparency and honesty are of paramount importance and build trust between providers and patients.

Presented by: Sundeep Agrawal, MD, U.S. Food and Drug Administration, Washington, District Of Columbia

Written By: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, Philadelphia, Pennsylvania, @selmasic, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona