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AUSTIN, Texas -- Unresectable nonmetastatic kidney cancers regressed substantially, but not completely, in response to treatment with nivolumab (Opdivo) and ipilimumab (Yervoy), a small prospective study showed.

Six of eight patients had tumor regression that averaged 31%, and all eight patients had stable disease or better as best response. Although no patient met the primary endpoint of complete tumor regression, the observed activity warrants further consideration for patients who are not candidates for ablative therapy or have unresectable tumors, said Ilya Tsimafeyeu, MD, of the Kidney Cancer Research Bureau in Moscow, during the International Kidney Cancer Symposium.

"I do believe we can treat primary tumors without any metastases with systemic therapy," he said. "Our objective was to achieve complete response, and we did not achieve that in any patient. However, we did observe objective responses, and the depth of response appeared to increase over time, even after we stopped treatment."

"Globally, we need to evaluate other combinations or addition of other therapy," Tsimafeyeu added. "We have not planned a larger study, but we will continue to follow these patients for 3 years, and we have frozen tumor samples to study going forward."

Though limited by the small number of patients, the study is interesting because of its applicability to clinical practice, said Shawn Dason, MD, of Ohio State University in Columbus.

"Sometimes this comes up, and we may not necessarily be using [systemic therapy] for this indication," said Dason. "I just had a patient where there was a level four thrombus on one side and a 2-cm mass and no metastatic disease. So I operated on the one side, and I told the patient they would go on adjuvant immunotherapy. The main question the patient had was 'Well, will that cure my other mass?'"

"I don't think there's much data on using immunotherapy for a stage I, small renal mass," Dason continued. "At least now we know it's probably going to stay stable, maybe improve, but it's not going to increase." He noted that the findings were consistent with an analysis of a randomized trial involving nivolumab/ipilimumab, where no patients had a complete response in their primary tumor.

Surgery remains the standard of care for localized renal cell carcinoma (RCC). Systemic therapy warrants consideration only for patients who have contraindications to surgery, Tsimafeyeu noted in the introduction to the study. In the phase III CheckMate 214 trial in metastatic RCC, nivolumab/ipilimumab had a significant impact on tumor burden despite a complete response rate of 11%. An intention-to-treat analysis showed that only 5% of patients had a complete response at the first follow-up scan.

Tsimafeyeu and colleagues tested the hypothesis that the combination of nivolumab and ipilimumab would achieve complete response in the primary tumor in patients with T1N0M0 RCC ineligible for surgery or ablative therapy. Secondary objectives were objective response rate (ORR), 3-year disease-free survival, 5-year cancer-specific survival, and adverse events. The statistical designed allowed investigators to reject the null hypothesis if at least three patients achieved objective responses.

Eligibility criteria included cytologically proven clear-cell RCC, CT-confirmed measurable tumor <4 cm with no evidence of extranodal metastatic disease, inability to have surgery or ablative treatment for any reason, and no prior therapy for RCC. Treatment consisted of ipilimumab every 3 weeks for a total of four doses, followed by nivolumab every 2 weeks for a total of eight doses.

The cohort had a median age of 78 years, 62.5% had centrally located tumors, and 75% had comorbid conditions. All patients received the planned immunotherapy without any grade ≥2 adverse events.

During a median follow-up of 17 months, no patient achieved a complete response. Four patients had partial responses and the remaining four had stable disease, resulting in a disease control rate of 100%. Six of the eight patients had some degree of tumor regression. Median tumor size declined from 3.1 cm at baseline to 2.0 cm after treatment. One patient had a 0.5-cm increase in tumor size at 9 months but was treated with stereotactic body radiotherapy, which led to tumor regression. The cohort had a 1-year PFS of 100%.

Although the trial did not evaluate neoadjuvant therapy, Tsimafeyeu told 麻豆传媒 the regimen might be useful for shrinking larger, nonmetastatic tumors prior to surgery or to improve the odds for surgery.

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