Immunotherapy combination shrinks tumors in surgery-ineligible renal cell carcinoma
Click Here to Manage Email Alerts
Most patients with renal cell carcinoma ineligible for surgery and ablation achieved tumor reduction after treatment with nivolumab plus ipilimumab, according to study results.
The combination also appeared safe for individuals with moderate or severe comorbidities, findings presented at International Kidney Cancer Symposium: North America showed.
Surgery is standard curative-intent therapy for patients with localized renal cell carcinoma. Consequently, only those with contraindications to surgery should undergo systemic therapy, according to study background.
The randomized phase 3 CheckMate 214 trial showed the combination of the anti-PD-1 antibody nivolumab (Opdivo, Bristol Myers Squibb) and the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) considerably reduced tumor burden among patients with intermediate- or poor-risk metastatic renal cell carcinoma. Eleven percent of patients achieved complete response, and 5% of those who achieved complete response did so on their first scan.
Ilya Tsimafeyeu, MD, director of Bureau for the Study of Kidney Cancer in Russia, and colleagues hypothesized that the immunotherapy combination may eliminate primary tumors among patients with T1aN0M0 disease ineligible for surgical treatment.
Researchers conducted a prospective, nonrandomized phase 2 pilot study that featured a Simon’s two-stage design.
Study protocol specified that three adults accrued in the first stage would undergo treatment with nivolumab and ipilimumab. If no patients achieved complete response, the study would be stopped. If the study proceeded to a second stage, five more adults would be accrued and receive the combination.
Primary inclusion criteria included cytologically proven clear cell renal cell carcinoma, CT-confirmed measurable primary tumor less than 4 cm with no evidence of extranodal metastatic disease, and inability to have or preference to avoid surgery or ablation for any reason. Exclusion criteria included prior treatment for renal cell carcinoma; history of serious hypertension, cardiac arrhythmia, congestive heart failure, angina pectoris or other severe cardiovascular disease; evidence of metastatic disease; local or systemic infections that required antibiotics within 28 days of study entry; autoimmune disease; or other malignancy. Women who were pregnant or nursing also were excluded.
Study participants received 1 mg/kg IV ipilimumab every 3 weeks for four doses, followed by 3 mg/kg IV nivolumab every 2 weeks for 16 weeks.
Patients underwent CT exams at 12 weeks and 16 weeks. Those who achieved complete response would continue treatment with the combination for an additional 6 weeks, whereas those who achieved partial response or exhibited stable disease would receive the combination for the next 12 weeks and be re-evaluated.
Complete response rate served as the primary endpoint. Secondary endpoints included response rate, 3-year DFS, 5-year cancer-specific survival and adverse event rate.
The study proceeded to the second stage, with eight patients (median age, 77.9 years; range, 73-89; 75% female; 100% white) included between February 2020 and June 2021. Patients had ECOG performance status of 0 (75%) or 1 (25%). Three (37.5%) had moderate comorbidities and three (37.5%) had severe comorbidities.
After median follow-up of 17 months, researchers reported no complete responses. Four patients (50%) achieved partial response and four (50%) exhibited stable disease.
Six patients (75%) exhibited reduction in tumor size, with a median change in sum of diameters of 30.9%.
After 9 months, only one patient had tumor enlargement of 0.5 cm. This patient underwent stereotactic body radiotherapy.
Researchers reported no grade 2 or higher adverse events.
All patients remained progression free at 1 year and remained on active surveillance at data cutoff.
Collapse
Tsimafeyeu I, et al. Abstract 41. Presented at: International Kidney Cancer Symposium: North America; Nov. 4-5, 2022; Austin, Texas.
Click Here to Manage Email Alerts