Adding Targeted Agent to Perioperative Therapy for RCC May Improve Disease Control

LOUISVILLE, Ky. — Tumor outcomes and thrombus control in renal cell carcinoma (RCC) improved with perioperative treatment that included a targeted agent plus immunotherapy, a small retrospective analysis showed.

Immuno-oncology (IO) followed by a tyrosine kinase inhibitor (TKI) led to an objective response rate of 32.1% versus 22.2% in patients who received an IO regimen before and after surgery. Downstaging of inferior vena cava (IVC) thrombus increased from 37.5% with IO/IO treatment to 45.5% with an IO/TKI regimen. Progression-free survival (PFS) improved with increasing amounts of post-treatment tumor necrosis, which was higher with IO/TKI.

Immune-related adverse events occurred significantly more often with IO/IO regimens (63% vs 29%, P=0.01), reported Wadih Issa, MD, of the University of Texas Southwestern Medical Center in Dallas, at the International Kidney Cancer Symposium (IKCS).

“Patients treated with perioperative IO/TKI tend to have more reduction in primary tumors and more tumor necrosis after treatment,” Issa and colleagues concluded in a poster presentation. “Tumor necrosis post-IO might be indicative of treatment effect and could be predictive of treatment response.”

The findings are informative for ongoing prospective trials of perioperative therapy and IVC thrombus trials, they added. Larger cohorts are needed to achieve statistical significance.

The study added to a limited database about the effects of perioperative IO combinations, which have emerged as standard of care for RCC, the investigators noted. In particular, optimal use of pre-nephrectomy regimens (IO/IO vs IO/TKI) remains understudied.

The investigators retrospectively reviewed records for 55 patients who received perioperative therapy for RCC, 28 who received IO/TKI, and 27 who received IO/IO. The two groups were similar with the exception that patients in the IO/TKI group were evenly distributed between locally advanced and metastatic disease, whereas the IO/IO group predominantly had metastatic disease (85%).

IO Combo Holds Advantage Over Single-Agent TKI

An early survival advantage in advanced RCC persisted out to 8 years with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) versus sunitinib (Sutent), an updated analysis of the randomized CheckMate 214 trial showed.

Patients treated with the IO combination had a median overall survival (OS) of 52.7 months versus 37.8 months with single-agent sunitinib (HR 0.72, 95% CI 0.62-0.83). RCC-specific survival also favored the combination (74 vs 45 months). PFS did not differ significantly between the two groups (~12 months in each group). Subgroup analyses showed significant OS and PFS improvements in intermediate- and poor-risk disease but not favorable-risk patients. The OS hazard ratio for favorable-risk patients improved over time from 1.45 at the primary analysis after 25 months of follow-up to 0.82 after 99.1 months of follow-up.

“Responses to nivolumab/ipilimumab were deep and durable in the overall study population,” concluded Hans J. Hammers, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas, and co-investigators. “Patients had notably improved duration of response and more complete responses with nivolumab/ipilimumab over sunitinib regardless of [disease risk category].”

“These results represent the longest follow-up in a phase III trial of checkpoint inhibitor combination therapy in first-line advanced RCC and continue to support nivolumab/ipilimumab as standard of care,” they added.

The multinational CheckMate 214 trial involved 1,096 patients with newly diagnosed advanced RCC, 847 of whom were classified as intermediate/poor risk. They were randomized to nivolumab plus ipilimumab or sunitinib. The primary endpoint was OS. An early analysis showed a higher response rate and better PFS with sunitinib in favorable-risk patients, but those advantages did not translate into an OS benefit.

Metastasectomy May Extend Survival

Selective surgery for metastatic RCC showed promise for slowing disease progression and extending survival, results of a prospective study suggested.

Three-fourths of patients who underwent metastasectomy met the primary outcome of no disease progression at 24 weeks. The 84-patient cohort had a median PFS of 11.6 months and median OS of 72 months.

“Metastasectomy was associated with a high probability of success at 24 weeks … in a group of predominantly intermediate-risk patients with metastatic RCC amenable to surgery,” concluded Muhammed Onel, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues. “These data provide further evidence that surgical intervention in selected patients with metastatic RCC may be associated with delayed disease progression and prolonged OS.”

The non-randomized, phase II study had its origin in previous studies of metastatic RCC suggesting that metastasectomy has potential to improve survival for patients with few curative treatment options. The trial involved patients with metastatic disease who were scheduled for surgery to achieve a radiographically disease-free state or to manage symptoms and “threatening” lesions. The primary endpoint was success rate, defined as no progression at 24 weeks.

The results showed that 62 of 84 (73.8%) patients met the goal of no disease progression 24 weeks after surgery.

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