Director Bureau for Cancer Research New York, NY, United States
Background: We hypothesized that immunotherapy could eliminate the primary tumor in T1aN0M0 RCC patients ineligible for surgery and nephron-sparing interventions.
Methods: In phase 2 pilot study patients with biopsy-proven clear-cell RCC of ≤4 cm (cT1a), no evidence of metastases, and unable to have surgery or ablation received ipilimumab (1 mg/kg) every 3 weeks for four doses, and nivolumab (240 mg) every 2 weeks during 16 weeks. The primary endpoint was complete response rate. Simon's two-stage design was used. The H0 that the true complete response rate was 11%. This design yields a type I error rate of 0.05 and power of 0.9 when the true complete response rate is 60% (Ha). The null hypothesis should be rejected if 3 or more responses are observed in 8 patients.
Results: Between February 2020 and June 2021, 8 patients were included. Median age was 77.9 years (range 73-89). Patients were predominantly male (75%), 62.5% had centrally located RCC, 25% had ECOG PS 1, and 75% had comorbidities. All patients completed immunotherapy without grade ≥2 adverse events. With a median follow-up of 15 months (95% CI 7.0–20.5), 1-year progression-free survival was 100%. No complete responses were observed. Partial responses were found in 3 patients (37.5%). Primary tumor continued to shrink after completion of therapy. Median size of the primary at RCC diagnosis and after immunotherapy was 3.11 cm (range 2.2–3.9) and 2.05 cm (1.2–4.0), respectively. Any shrinkage of the primary tumor was reported in 5 (62.5%) patients (change in median sum of diameters -21%). Only one patient had tumor enlargement (+0.5 cm (+13%) after 9 months.
Conclusions: The complete regression of the primary tumor in T1aN0M0 RCC patients who received immunotherapy was not observed. However, we found a reduction in tumor size in half of the patients. Treatment with nivolumab and ipilimumab was safe in patients with comorbidities.
